Deep Vein Thrombosis

Deep vein thrombosis
Straight to the point of care
Last updated: Mar 10, 2022

Table of Contents
Overview 3
Summary 3
Definition 3
Theory 4
Epidemiology 4
Risk factors 4
Aetiology 8
Pathophysiology 9
Classification 9
Case history 11
Diagnosis 13
Recommendations 13
History and exam 25
Investigations 29
Differentials 35
Criteria 36
Screening 37
Management 39
Recommendations 39
Treatment algorithm overview 52
Treatment algorithm 54
Primary prevention 79
Secondary prevention 81
Patient discussions 83
Follow up 85
Monitoring 85
Complications 86
Prognosis 88
Guidelines 90
Diagnostic guidelines 90
Treatment guidelines 92
Online resources 95
References 96
Images 109
Disclaimer 111
Deep vein thrombosis Overview
Summary
Deep vein thrombosis (DVT) is the development of a blood clot within a vein deep to the muscular tissue
planes.
OVERVIEW
Patients who develop DVT commonly have risk factors, such as active cancer, trauma, major surgery,
hospitalisation, immobilisation, pregnancy, or oral contraceptive use. DVT may also be unprovoked
(idiopathic) and occur in the absence of any identifiable extrinsic risk factors.
DVTs commonly cause asymmetrical leg swelling, unilateral leg pain, dilation or distension of superficial
veins, and red or discolored skin, but can also be asymptomatic.
Assessment of pre-test probability (using a validated score such as Wells) is key if DVT is suspected, and
should be used in combination with an algorithmic diagnostic approach to avoid unnecessary imaging when
the likelihood of DVT is low.
Diagnosis requires confirmation of a blood clot in a deep vein in the leg, pelvis, or vena cava by venous
ultrasound imaging (or other imaging techniques such as computed tomography scan).
DVT is usually treated with anticoagulants such as unfractionated heparin, low molecular weight heparin,
fondaparinux, rivaroxaban, apixaban, edoxaban, dabigatran, and/or warfarin. Interventional therapies,
including thrombolysis, are rarely indicated.
Generally, anticoagulant therapy for at least 3 months is required for patients with DVT. Thereafter, continued
anticoagulant therapy for secondary prevention is indicated in selected patients to reduce the risk of recurrent
events.
Post-thrombotic syndrome may occur with symptoms of chronic pain, swelling, skin discoloration, or venous
ulcers following chronic obstruction of venous outflow and/or incompetence of venous valves.
Definition
DVT is the development of a blood clot in a major deep vein in the leg, thigh, pelvis, or abdomen. It may also
occur in less common locations such as the arm veins; the portal, mesenteric, ovarian, or retinal veins; or
the veins and venous sinuses of the brain. DVT can result in impaired venous blood flow. DVT is rarely life-
threatening on its own, but has the potential to cause pulmonary embolism (PE), which can be fatal. Venous
thromboembolism is the broad term that includes DVT and PE. Superficial vein thrombophlebitis (also known
as superficial vein thrombosis), a common related condition, affects veins superficial to the musculature. This
topic focuses on the diagnosis and management of lower-extremity DVT.
This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Mar 10, 2022.
BMJ Best Practice topics are regularly updated and the most recent version
3
of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2023. All rights reserved.
Deep vein thrombosis Theory
Epidemiology
Venous thromboembolism (VTE) is a relatively common medical problem with a yearly incidence of
approximately 1 in every 1000 adults.[1] [2] [3] Approximately two-thirds present as DVT alone, and one third
THEORY
present as pulmonary embolism (with or without concomitant symptoms of DVT).[2]
The incidence of DVT during pregnancy or the postnatal period is approximately 1 per 1000 live births.[4]
Other clinical characteristics confer widely variable incidences of DVT. For instance, orthopaedic surgery
patients have a DVT incidence ranging from approximately 1% to 4% depending on the utilisation of
pharmacological prophylaxis, while the incidence in acutely ill medical patients is approximately 0.5% to 6%,
depending heavily on the method of diagnosis, inclusion of asymptomatic versus only symptomatic VTE,
utilisation of pharmacological prophylaxis, and duration of follow-up.[5] In critically ill patients, an incidence
as high as 37.2% has been reported.[6] The population incidence is increasing slowly as the proportion of
the population that is older increases, and as testing for DVT using ultrasound and testing for pulmonary
embolism using multi-detector chest computed tomographic angiography increases.
Risk factors
Strong
recently bedridden for 3 days or more
This is a component of the Wells score.[12]
Venous stasis and prolonged bed rest are known to increase the risk of venous thromboembolism.[18]
major surgery within the preceding 12 weeks

Major surgery is a particularly significant risk if the patient required general or regional anaesthesia, as
this is a component of the Wells score.[12]
Approximately 18% of all incident venous thromboembolism occurs within 3 months of major surgery.
Reasons include postoperative immobilisation, inflammation, underlying comorbidity, and injury to the
venous system in selected cases (e.g., total knee replacement).[3]
medical hospitalisation within the preceding 2 months

Approximately 20% of all incident venous thromboembolism (VTE) occurs either during a medical
hospitalisation or within 2 months of a hospitalisation of 4 or more days.[1] [2]
Reasons are the combination of immobilisation with acute and chronic medical comorbidities that are
associated with VTE development, such as acute infection, heart failure, stroke, respiratory failure, and
inflammatory conditions.[19] [20] [21] [22] The use of intravenous catheters predisposes to hospital-
associated DVT, both in the upper and lower extremities.[23]
active cancer
Active cancer is particularly significant if treatment is ongoing, within 6 months, or palliative; this is a
component of the Wells score.[12] [24] [25] [26] [27]
Many malignancies increase the risk for thrombosis through a variety of mechanisms, including
activation of the coagulation system and restriction of flow due to vein compression. DVT rates are
4 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Mar 10, 2022.
likely to be 4- to 7.5-fold higher in patients with cancer than in the general population,[24] and patients
with metastatic cancer at the time of diagnosis are at especially increased risk.[25] Cancer-related
therapies including surgery, some chemotherapeutic and biological agents, and use of vascular
access devices also increase the risk of DVT.
THEORY
previous venous thromboembolic event
Previous venous thromboembolism (VTE) is a component of the Wells score.[12]
Previous VTE predicts the risk for future events, with the magnitude of the risk being dependent on the
presence or absence of provoking factors at the time of the initial event, sex of the patient, and other
factors. In one systematic review, the rate of recurrence was 3.3% per patient-year for patients with a
previous DVT due to a transient risk factor, and 7.4% per patient-year for patients with an unprovoked
DVT.[28]
recent trauma or fracture

Paralysis, paresis, or recent plaster immobilisation of the lower extremities is a component of the Wells
score.[12]
Patients with severe trauma are at increased risk of DVT even when the lower extremities are not
involved.[29] [30]
Patients with lower-extremity injuries that require surgery, such as leg, femur, or hip fracture, are at
particularly increased risk, owing to vein injury coupled with effects of immobilisation and surgery.[31]
Non-surgical injuries (e.g., a fracture that requires casting) also increase the risk.
increasing age
The risk of venous thromboembolism, especially of a first episode, increases exponentially with age.[1]
[3] [32] Reasons likely include increased medical comorbidities, declining mobility, and perhaps age-
related changes in coagulation.
pregnancy and the postnatal period

There is a more than 4-fold increased risk of thrombosis throughout gestation, and this risk may
increase during the postnatal period.[33] [34] [35] While the relative risk for DVT during pregnancy and
the postnatal period is substantially elevated, the absolute risk remains low.
paralysis, paresis, or recent plaster immobilisation of the lower extremities

This is a component of the Wells score.[12] Venous stasis and prolonged bed rest are known to
increase the risk of venous thromboembolism.[18]
factor V Leiden
The factor V Leiden (FVL) mutation creates a variant factor V that is resistant to activated protein C.
The relative risk of developing venous thromboembolism (VTE; particularly DVT) is approximately 3
to 4 times greater in patients who carry 1 copy of the FVL mutation (heterozygotes) compared with
patients without this mutation. However, the absolute lifetime risk of developing VTE is low.
There is a strong interaction between use of oral contraceptives or hormone replacement therapy
containing oestrogen and presence of FVL, likely because oestrogen also confers resistance to
5
activated protein C. The relative risk increase of VTE is approximately 12-fold that of a non-carrier who
does not use oestrogen.[36]
Homozygous carriers have a substantially higher risk of developing VTE compared with heterozygotes.
THEORY
FVL carriers appear to have increased risk for DVT only, not for pulmonary embolism, an observation
called the 'factor V Leiden paradox'.[37]
prothrombin gene G20210A mutation

The prothrombin gene mutation is caused by a single nucleotide polymorphism (G20210A).
Affected patients produce an excess amount of prothrombin. The relative risk of developing venous
thromboembolism (VTE) is approximately 4 times greater than the unaffected population, but the
absolute risk of thrombosis remains low.
There is a strong interaction between use of oral contraceptives or hormone replacement therapy
containing oestrogen and presence of the prothrombin variant, with an approximately 7-fold increase in
the risk of VTE.[36]
Homozygous carriers of the prothrombin gene mutation have substantially greater risk of developing
VTE compared with heterozygotes.
protein C or protein S deficiency

Patients with a well-defined deficiency in protein C or protein S have a 5- to 6-fold greater risk of
developing venous thromboembolic events, although the magnitude of this risk varies according
to the degree of functional loss present.[36] The absolute risk of first pregnancy-associated
venous thromboembolism (VTE) is 7.8% in protein C-deficient women and 4.8% in protein S-
deficient women.[38] Thrombosis risk increases in a multiplicative fashion in the presence of other
thrombophilic disorders. Both disorders are rare.
antithrombin deficiency
The prevalence of antithrombin deficiency disorders is low in cohorts of patients with venous
thromboembolism (VTE; <1%). The magnitude of thrombosis risk varies depending on the degree of
functional loss present. The absolute risk of first pregnancy-associated VTE in antithrombin-deficient
women is 16.6%.[38]
antiphospholipid antibody syndrome

Defined as an association of persistently detectable antiphospholipid antibodies with specified clinical
features consisting of thrombosis and/or pregnancy-related morbidity, antiphospholipid antibody
syndrome is often over-diagnosed, likely due to the relatively complex criteria for diagnosis and the
possibility of false-positive laboratory tests. Criteria have been updated and clarified.[39]
In contrast to the hereditary thrombophilias, antiphospholipid syndrome likely predicts a higher

risk for both initial and recurrent venous thromboembolism (VTE), and may be useful in informing
decisions regarding use of anticoagulation for secondary prevention after the initial treatment of a VTE
event.[40] Antiphospholipid antibodies have been reported in up to 14% of patients presenting with a
VTE.[41]
medical comorbidity
Increased venous thromboembolism (VTE) risk occurs especially with inflammation, infection, and
immobility.
THEORY
Case reports and small series show greater incidence in patients with sickle cell anaemia,
inflammatory bowel disease, Behcet's disease, HIV, primary pulmonary hypertension, hyperlipidaemia,
diabetes mellitus, myeloproliferative diseases, and others, including systemic lupus erythematosus.[42]
Several medical disorders, especially heart failure, respiratory disease, acute ischaemic stroke, and
acute infections, are associated with hospital-acquired DVT, though the incidence of DVT continues to
accumulate for about 2 months after hospital admission.[19] [20] [21] [22]
Liver disease, even when causing prolongation of coagulation times, increases the risk for
thrombosis.[43]
Mechanical ventilation has been associated with increased DVT in many studies of critically ill patients,
though may be a marker of disease severity and underlying respiratory disease.[6] [44] [45]
Coronavirus disease 2019 (COVID-19), an infection caused by the novel coronavirus severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with risk for VTE, though
the risk for pulmonary embolism may predominate over the risk for DVT.[9] See our topic Coronavirus
disease 2019 (COVID-19).
use of specific drugs

The absolute risk of developing a DVT in women who take oestrogen-containing oral contraceptives
is low. The risk of developing an oral contraceptive-related DVT is associated with the presence of a
classic thrombophilia and is also associated with obesity and smoking. Risk is greatest in the first year
of use.
For contraceptives, all preparations that contain oestrogen are associated with risk for venous
thromboembolism (VTE). Mechanism of delivery (oral, transdermal, transvaginal) and the 'generation'
of oral combined contraceptives are associated with broadly similar risks.[46] [47] However, oral
contraceptive pills containing third-generation progestins (such as desogestrel) or fourth-generation
progestins (such as drospirenone) may be associated with greater risk of VTE compared with
levonorgestrel.[48] [49] When used for the indication of hormone replacement, the transdermal route
appears to confer less risk than the oral route.[46] [47]
Tamoxifen and raloxifen are associated with a 2- to 3-fold relative risk of developing DVT, particularly in
patients with a thrombophilic condition, such as factor V Leiden.
Thalidomide most commonly causes DVT when used as a cancer chemotherapeutic agent. Many
other chemotherapeutic agents can also increase the risk. Concomitant prophylaxis is suggested for
certain diseases and regimens.[50]
Erythropoietin is associated with an increased risk of DVT in patients with cancer.
Patients who develop antibodies to adalimumab (a tumour necrosis factor alpha inhibitor) frequently
develop venous thrombosis.[51]
7
Androgen-deprivation therapies used in prostate cancer increase VTE risk between about 1.5- and
2.5-fold depending upon the agent.[52]
Testosterone replacement therapy, both in men with and without demonstrable hypogonadism, has
THEORY
been associated with a 2-fold increased VTE risk.[53]
Non-steroidal anti-inflammatory drugs (NSAIDs), as a class, are associated with an increased rate of
VTE. Risk attributable to individual NSAIDs is unknown.[54] [55]
Weak
obesity
Randomised clinical trials and retrospective cohort studies have shown that high body mass index
(especially >30 kg/m²) is associated significantly with DVT development.[32] [56]
Mechanisms may include relative immobilisation, reduced venous flow rates, underlying inflammatory
state, and greater frequency of co-existing comorbidities.
cigaret te smoking
The Emerging Risk Factors Collaboration (731,728 participants) found a correlation between current
smoking and the risk of venous thromboembolism, with a hazard ratio of 1.38.[32]
recent long-distance air travel

The absolute risk with air travel appears to be small. The risk appears to be increased in patients
with an elevated baseline risk of venous thromboembolism (VTE) such as those with a previous
VTE, recent surgery or trauma, obesity, limited mobility, or advanced age. The duration of flight
associated with increased risk is uncertain, but flights longer than about 4 hours are likely associated
with elevated risk.[57]
family history
Family history of DVT or pulmonary embolism may increase the risk.[56] The strength of
the association varies, depending on the number of affected family members and degree of
relatedness.[58]
Aetiology
The coagulation system in blood is complex and highly regulated. Slight alterations in the systems that
regulate coagulation can lead to bleeding or thrombosis.[7] The three factors that, individually or together,
lead to most DVTs are vessel injury, venous stasis, and activation of the clotting system (known as Virchow's
triad). Therefore, patients who develop DVT typically experience a trigger that leads to blood coagulation
(e.g., surgery or trauma that activates the coagulation system), prolonged immobility that leads to stasis,
or medications or illnesses (e.g., cancers, antiphospholipid syndrome) that can stimulate clotting.[8]
Susceptibility to thrombosis is genetically mediated. Several genetic variants in the coagulation system
itself (e.g., the factor V Leiden mutation) as well as outside the coagulation system (e.g., non-O blood type)
increase the risk of thrombosis. All of these factors may interact, further increasing the risk of DVT.
There is a clear association between DVT and the following:
• Active cancer
• Recent major surgery (especially major orthopaedic procedures)
• Recent hospitalisation
• Recent trauma
• Medical illness (especially diseases associated with inflammation, such as acute infection)
THEORY
• Hormone replacement and oral contraceptive oestrogen therapy.
Coronavirus disease 2019 (COVID-19), an infection caused by the novel coronavirus severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with risk for VTE.[9] See our
topic Coronavirus disease 2019 (COVID-19) for more information.
The presence or absence and timing of risk factors relative to the diagnosis of DVT has a major impact
on determining the duration of anticoagulant therapy.[10] The International Society on Thrombosis and
Haemostasis has published a 4-category system of classification (presented in order of increasing risk of
recurrent venous thromboembolism after an initial episode), which is consistent with UK National Institute for
Health and Care Excellence guidance:[11] [12]
• Major transient risk factors (e.g., major surgery; trauma; significant immobility (bedbound, unable to
walk unaided, or likely to spend a substantial proportion of the day in bed or in a chair); pregnancy or
puerperium; use of oral contraceptive/hormone replacement therapy), occurring within 3 months prior
to thrombosis[12]
• Minor transient risk factors (e.g., minor surgery), occurring within 2 months prior to thrombosis
• Unprovoked (no pre-existing, major, transient provoking risk factor in the prior 3 months)[12]
• Persistent risk factors (e.g., active cancer, autoimmune conditions such as systemic lupus
erythematosus and inflammatory bowel disease).
The European Society of Cardiology guideline employs a similar framework, with some differences in
terminology.[13]
Pathophysiology
Most blood clots that develop in the deep venous system of the leg begin to form just above and behind a
venous valve.[14] [15]
Clots often resolve spontaneously. When propagation of the thrombus does occur, it expands and grows
proximally and across the lumen of the vein. A clot might occlude the entire lumen, but it is more commonly
located on one peripheral aspect of the lumen. Even when the entire lumen appears to be occluded, a
small amount of flow may continue on the extreme periphery of the clot. Many DVTs arise in the calf veins
and propagate proximally. However, in some instances, such as during pregnancy or following total hip
arthroplasty, the clot might form initially in the groin or iliac vein region.[15] These DVTs may propagate into
the more distal veins. DVTs may arise in more than one separated venous segment at the same time.
Acute thrombus begins to be dissolved by the body's fibrinolytic system as soon as a clot begins to form.
Thus, elevated levels of breakdown products of cross-linked fibrin, particularly the fragment called D-
dimer, appear in the blood soon after a clot begins to form. Therefore, testing for D-dimer is an important
component of the evidence-based approach to diagnosing suspected DVT.[16] [17]
Classification
9
DVT: lower extremity
The following is an informal clinical classification.
(a) Superficial versus deep

THEORY
• Superficial vein thrombophlebitis (SVT; also known as superficial vein thrombosis). See our topic
Superficial vein thrombophlebitis.
• Palpable thrombi in subcutaneous veins just below the skin (e.g., in a varicose vein) are
classified as SVT; also referred to as superficial thrombophlebitis.
• Most SVT confer less risk of complications than DVT and are managed differently. However,
thrombi in the proximal portion of the greater saphenous vein (especially if within a few
centimetres of the sapheno-femoral junction) may pose some risk of propagation and pulmonary
embolisation because the greater saphenous vein joins the common femoral vein in the groin.
SVT in the proximal greater saphenous vein are often managed in the same way as DVT.
• Deep vein thrombosis
• Thrombi form within veins deep to the muscular tissue planes.
(b) Proximal versus distal
• Proximal venous thrombosis
• DVTs in the popliteal or more proximal (femoral, deep femoral, common femoral, iliac, and vena
cava) deep veins are classified as proximal.
• Distal or calf vein thrombosis
• DVTs in the three major axial calf veins (posterior tibial, anterior tibial, peroneal) below
the popliteal vein and clots in the muscular vein branches (gastrocnemius and soleus) are
considered distal deep calf vein thrombi. Some people may have anatomical variation of
the distal deep veins, including paired peroneal veins, or a tibial-peroneal trunk rather than
an immediate trifurcation distal to the popliteal vein. Thrombi in these areas are also distal
DVTs. DVTs isolated to the distal veins have a lower risk of causing pulmonary embolism and
post-thrombotic syndrome.
(c) Acute versus subacute, or chronic
• Acute venous thrombosis confirmed by duplex ultrasound has the following characteristics: vein width
at site of the thrombus is wider than the unaffected vein on the contralateral side (i.e., dilated vessel),
and ultrasound echos are not prominent (i.e., the clot is not echogenic). Acute DVT often correlates
with recent onset of symptoms. Acute clots may totally or partially obstruct flow.
• Subacute or chronic DVTs are associated with some narrowing of the vein, partial but incomplete
compressibility of the vessel, and hyperechogenicity in the vein lumen. The involved vein is normal-
sized or contracted. Chronic clots may totally or partially obstruct flow. Chronic DVT can occur with or
without anticoagulant treatment in symptomatic or asymptomatic DVT.
• The time over which an acute DVT takes on subacute or chronic characteristics on ultrasound has not
THEORY
been well validated, and likely varies between people. Distinguishing a new acute DVT from a prior
DVT is best accomplished by direct comparison with prior imaging studies.
DVT: upper extremity (not covered in this topic)

The following is an informal clinical classification.
(a) Superficial versus deep thrombosis
• Thrombi in subcutaneous veins just below the skin that are palpable on the forearm or upper arm (i.e.,
basilic and cephalic veins) are classified as superficial.
• Brachial, axillary, subclavian, or innominate (or brachiocephalic) veins, and the superior vena cava are
classified as deep. The internal jugular vein is also considered to be a deep vein.
(b) Proximal versus distal
• The distinction of proximal versus distal DVT is not clearly defined for the upper extremity.
Management studies of upper extremity DVT have often included cases involving the axillary and more
proximal veins. The risk of embolisation, and management of DVT in the brachial vein, is less certain.
(c) Acute versus subacute, or chronic
• Criteria are similar to lower-extremity venous thrombosis. However, inability to compress the
subclavian and other centrally located veins makes diagnosis and classification more difficult.
Case history
Case history #1
A 65-year-old woman presents with unilateral leg pain and swelling of 5 days' duration. She has a history
of hypertension, congestive heart failure, and recent hospitalisation for a total knee replacement. She had
been recuperating at home but on beginning to walk, her right leg became painful, tender, and swollen.
On examination there is pitting oedema on the right and the right calf is 4 cm greater in circumference
than the left when measured 10 cm below the tibial tuberosity. Superficial veins on the right foot are more
dilated than on the left and easily visible. The right leg is slightly redder than the left. There is tenderness
on palpation in the popliteal fossa behind the right knee.
Other presentations
Patients may also present with concomitant pulmonary embolism (PE), with symptoms such as shortness
of breath, chest pain, and dyspnoea. PE should always be considered in any patient with an acute DVT.
11
In severe DVT, massive swelling can obstruct superficial venous return as well as arterial inflow, leading
to a life- and limb-threatening condition known as phlegmasia cerulea dolens. The leg may be severely
swollen, painful, and ischaemic. Most patients who present with superficial venous thrombosis (SVT) have
a tender palpable cord under the skin. However, about one quarter of patients with signs and symptoms of
THEORY
SVT on examination will also be found to have DVT when ultrasound is performed.
Deep vein thrombosis Diagnosis
Recommendations
Key Recommendations
Suspect DVT based on the patient’s clinical presentation, and any risk factors for DVT.
• Symptoms and signs of DVT are usually unilateral, and include:
• Calf swelling (or, more rarely, swelling of the entire leg)

• Localised pain along the deep venous system
• Oedema
• Dilated superficial veins over the foot and leg
• Redness and warmth
• Coolness
• Blue discoloration (cyanosis).
• Significant risk factors include:
• Recently bedridden for 3 days or more, or major surgery within 12 weeks requiring general or
regional anaesthesia[12] [26]
• Medical hospitalisation within the preceding 2 months[1] [2]
• Active cancer (treatment ongoing, within 6 months, or palliative)[12] [24] [25] [26]
• Previous venous thromboembolic event[12] [26] [27]
• Recent trauma or fracture[29] [30]
• Increasing age[1] [3] [32]
• Pregnancy and the postnatal period[33] [34] [35]
• Paralysis, paresis, or recent plaster immobilisation of the lower extremities[12] [18] [26]
• Hereditary thrombophilia (e.g., factor V Leiden, prothrombin gene G20210A mutation, protein
C or protein S deficiency)
• Presence of medical comorbidities
• Certain drugs (e.g., oestrogen-containing oral contraceptives).
DIAGNOSIS
If you suspect phlegmasia cerulea dolens (marked swelling, significant pain, and cyanosis) start
immediate treatment; do not wait for the results of investigations because this is a life- and limb-
threatening emergency.[81] See Phlegmasia cerulea dolens under Management recommendations.
Assess the pretest probability of DVT using the 2-level Wells score (unless the patient is pregnant) to
categorise the patient as ‘DVT likely’ (Wells score ≥2) or ‘DVT unlikely’ (Wells score <2).[12] [26] [27] Use
the Wells score in combination with a diagnostic algorithm.[12] [26] [27] The National Health Institute for
Health and Care Excellence (UK) recommends the following:[12]
• If the patient is categorised as ‘DVT likely', organise a venous ultrasound, with the result available
within 4 hours.[12] [60] Start therapeutic anticoagulation if DVT is confirmed[12]
• If the patient is categorised as ‘DVT unlikely’, order a D-dimer with the result available within 4
hours.[12]
Venous ultrasound is the first choice of imaging.[12] [26] [27] In the UK, different centres may use
either proximal or whole-leg venous ultrasound. Check your local protocol to determine the recommended
strategy. Consider using computed tomography (or magnetic resonance imaging) venography if venous
ultrasound is not available or inconclusive (unless the patient is pregnant).[26] [27]
13
Be aware that diagnosis of DVT is difficult in pregnancy; do not use the Wells score or D-dimer level
to diagnose or exclude DVT in these patients.[26] Consider the diagnosis of DVT in a pregnant patient
based on a high index of clinical suspicion and ensure close follow-up if DVT is confirmed.[26]
Confirm the diagnosis of DVT if imaging shows a blood clot in a deep vein in the leg, pelvis, or vena
cava.[12] [26] [27]
Full Recommendations
Diagnostic algorithm
Use a diagnostic algorithm to evaluate a patient with suspected DVT.
[Algorithm for the diagnosis of deep vein thrombosis]
History
Symptoms of DVT are usually unilateral, and include:
• Calf swelling (or, more rarely, swelling of the entire leg)
• Significant swelling, particularly in combination with severe pain and cyanosis, is a symptom
of phlegmasia cerulea dolens (PCD). PCD is a rare life-threatening complication that may
lead to arterial ischaemia and can ultimately cause gangrene with high amputation and
mortality rates.[81] [82] If you suspect PCD, start immediate treatment and refer the patient
to a vascular surgeon.[26] [82] This is a life- and limb-threatening emergency; do not wait for
the results of investigations to start treatment.[26] [82] See Phlegmasia cerulea dolens under
Management recommendations
• Localised pain along the deep venous system
• Pain is typically throbbing in nature, and comes on while walking or weight bearing[83]
• Oedema
•
DIAGNOSIS
Dilated superficial veins over the foot and leg

• Coolness
• Redness and warmth[83]
• Blue discoloration (cyanosis)
• This is also a symptom of PCD.
Symptoms range from severe to very subtle, and patients can be asymptomatic.
Ask about significant risk factors, which include:
• Active cancer (treatment ongoing, within 6 months, or palliative)[12] [24] [25] [26] [27]
• Recent trauma or fracture[29] [30]
• Paralysis, paresis, or recent plaster immobilisation of the lower extremities[12] [18] [26] [27]
• Hereditary thrombophilia (e.g., factor V Leiden, prothrombin gene G20210A mutation, protein C or
protein S deficiency)
Always ask about symptoms of concomitant pulmonary embolism.[26] [27] See our topic Pulmonary
embolism.
Physical examination
Assess unilateral leg swelling by measuring the circumference of the symptomatic leg 10 cm below the
tibial tuberosity; compare this with the asymptomatic leg. Any difference between the symptomatic and
asymptomatic leg increases the probability of DVT, and a difference of >3 cm between the extremities
further increases the probability; these are also elements of the Wells score - see Assessment of pretest
probability (Wells score) below.[12] [26] [27]
Examine the patient for:
• Oedema and dilated collateral superficial veins on the affected side

• Tenderness along the path of the deep veins (posterior calf compression, compression of the
popliteal fossa, and compression along the inner anterior thigh from the groin to the adductor canal)
• Coolness
• Redness and warmth
• Phlegmasia cerulea dolens (PCD); characterised by marked swelling, significant pain, and
cyanosis.[81] PCD is a rare life-threatening complication that may lead to arterial ischaemia and
can ultimately cause gangrene with high amputation and mortality rates.[81] [82] If you suspect
PCD, start immediate treatment and refer the patient to a vascular surgeon.[26] [82] This is a life-
and limb-threatening emergency; do not wait for the results of investigations to start treatment.[26]
[82] See Phlegmasia cerulea dolens under Management recommendations.
DIAGNOSIS
15
Phlegmasia cerulea dolens: swelling of the left leg and bluish discoloration of the foot
Cooper RM, et al. Phlegmasia cerulea dolens, a rare complication
of deep vein thrombosis. Emerg Med J. 2008 Jun;25(6):334
Always consider other causes for the patient’s presentation, including (see the Differentials section for
more information):[84]
• Large or ruptured popliteal cyst (Baker's cyst)

DIAGNOSIS
• Cellulitis
• Musculoskeletal trauma or injury (calf bleeding or haematoma, ruptured Achilles' tendon, or
ruptured plantaris tendon).
Practical tip
Bear in mind that DVT may also co-exist with other conditions, particularly cellulitis or a
musculoskeletal injury.
Always examine the patient for signs of concomitant pulmonary embolism; particularly aim to identify
more subtle signs that may be easily missed (e.g., sinus tachycardia and tachypnoea).[26] [27] See our
topic Pulmonary embolism.
Assessment of pretest probability (Wells score)

Assess the clinical probability of DVT using the Wells score (unless the patient is pregnant - see
Suspected DVT in pregnancybelow).[12] [26] [27]
• There are several risk assessment models available to assess the clinical probability of DVT;
however, the Wells score provides a reproducible method to determine the clinical probability of
DVT and is the most widely accepted and validated pretest probability tool used in diagnostic
algorithms for DVT.[26] [85] [86]
The two-level Wells score categorises patients as ‘DVT likely’ (Wells score ≥2) or ‘DVT unlikely’ (Wells
score <2).[12] [26] [27]
• A three-level iteration of the Wells score (where patients are categorised into low, moderate, or high
clinical likelihood of DVT) is available but the two-level score is generally preferred in practice.[26]
[27]
Practical tip
The Wells score may underestimate the probability of DVT in certain patient groups, such as
patients who misuse intravenous drugs.[87] In practice, categorise patients who inject drugs
into a femoral vein as ‘DVT likely’.
Wells#score elements Score
Active cancer (any treatment within past 6 1

months)
Calf swelling where affected calf circumference 1

measures >3 cm more than the other calf
(measured 10 cm below tibial tuberosity)
Prominent superficial veins (non-varicose) 1
Pitting oedema (confined to symptomatic leg) 1
Swelling of entire leg 1
Localised pain along distribution of deep venous 1

system
DIAGNOSIS
Paralysis, paresis, or recent cast immobilisation 1
of lower extremities
Recent bed rest for >3 days or major 1

surgery requiring regional or general
anaesthetic within past 12 weeks
Previous history of DVT or pulmonary embolism 1
Alternative diagnosis at least as probable 1
*Two versions of the risk assessment model have been validated: two categories (DVT unlikely or likely) or
three categories (low, intermediate, or high clinical probability. The simplified version (producing two score
categories) is presented as it is likely the easiest to use in clinical settings.
Use the Wells score in combination with a diagnostic algorithm - see Diagnostic algorithm above.[12] [26]
[27] The National Health Institute for Health and Care Excellence (UK) recommends the following:[12]
17
• If the patient is categorised as ‘DVT likely’, organise a venous ultrasound, with the result available
within 4 hours.[12] [60] Start therapeutic anticoagulation if proximal DVT is confirmed[12]
• If the patient is categorised as ‘DVT unlikely', order a D-dimer with the result available within 4
hours.[12]
See Quantitative D-dimer level and Venous ultrasound below for next steps, or if the results of
investigations aren’t available within 4 hours.
If a whole-leg ultrasound confirms distal (calf) DVT, check your local protocol for recommendations on
whether and how to start anticoagulation; there is debate in the guidelines.
• In the UK, common practice is to start anticoagulation unless the patient has a high risk of bleeding
or the DVT is not extensive (<5 cm). Seek advice from a haematologist if the patient has a high
bleeding risk or the DVT is not extensive. See Confirmed distal (calf) DVT under Management
recommendationsfor more information.
Quantitative D-dimer level

Suitability of D-dimer testing depends on:[12] [26] [27]
• Whether the patient’s Wells score has categorised the patient as ‘DVT likely’ (Wells ≥2) or ‘DVT
unlikely’ (Wells <2)
AND
• The availability of venous ultrasound.
If the patient is pregnant, do not use D-dimer testing (or the Wells score) to confirm or rule out DVT.[26]
[27] See Suspected DVT in pregnancy below for more information.
If D-dimer testing is indicated, consider:[12]
• Fully quantitative point-of-care D-dimer testing if laboratory facilities are not available (e.g., in a
primary care setting)
• An age-adjusted D-dimer test threshold if the patient is aged over 50 years.
DIAGNOSIS
Practical tip
If D-dimer testing is required, always order this before giving anticoagulation; a false negative D-
dimer result can occur if blood is drawn after giving anticoagulation.[26]
DVT likely (Wells ≥2)

Venous ultrasound is the first-line investigation for patients deemed ‘DVT likely’.[12] [26] [27] See Venous
ultrasound below. However, request D-dimer testing if the result of venous ultrasound is:[12]
• Negative
OR
• Not available within 4 hours. After the D-dimer test, start interim therapeutic anticoagulation, and
organise a venous ultrasound with the result available within 24 hours.[12]
DVT unlikely (Wells <2)

Request D-dimer testing for all patients categorised as ‘DVT unlikely’.[12] [26] [27]
• If the D-dimer level has been taken but the result is not available within 4 hours, start interim
therapeutic anticoagulation.
• If the D-dimer level is elevated, organise:[12]
• A venous ultrasound, with the result available within 4 hours
OR
• Interim therapeutic anticoagulation, and a venous ultrasound with the result available within
24 hours.
• A normal D-dimer level excludes the diagnosis of DVT; consider alternative causes.[12]
Practical tip
Be aware that an elevated D-dimer level is non-specific and is frequently abnormal in patients
without DVT who are older, are acutely ill, have underlying hepatic disease, have an infection, or are
pregnant.
More info: D-dimer
D-dimer is a breakdown product of cross-linked fibrin; if there is an acute clot, D-dimer level is likely
to be elevated. A quantitative or highly sensitive D-dimer test is therefore a useful test to exclude the
presence of an acute DVT.
There are many tests available for D-dimer, but the most reliable are highly sensitive enzyme-linked
immunosorbent assay tests. Each of the multiple tests that are available on the market has its own
normal cut-off value. D-dimer can be reported in different units, so the specific cut-off value for the test
being used should be noted.[88]
D-dimer has a high negative predictive value, which can reduce the need for further imaging or
immediate anticoagulation with its associated risks. However, D-dimer also has a low positive
predictive value, regardless of the patient group.
DIAGNOSIS
Venous ultrasound
Venous ultrasonography is the first-line method of imaging.[12] [26]
Choose to use venous ultrasound based on whether the patient’s Wells score has categorised them as
‘DVT likely’ or ‘DVT unlikely’, and the result of D-dimer testing (if this is indicated).[12] A positive venous
ultrasound confirms the diagnosis of DVT.[12] [26] [27]
In the UK, different centres may use either proximal or whole-leg venous ultrasound. Check your local
protocol to determine the recommended strategy.
• The UK National Institute for Health and Care Excellence (NICE) recommends using proximal
venous ultrasound only.[12] However, the European Society of Vascular Surgery recommends
whole-leg ultrasound if you suspect distal (calf) DVT.[26] Both strategies have advantages and
disadvantages.
19
More info: Ultrasound approaches
Diagnosis of DVT using B-mode ultrasound is based on the inability to completely collapse the walls of
the vein in the transverse plane by pressing down on the vein with a transducer probe (the presence of
thrombus prevents compression).
Short-axis ultrasound view showing the femoral vein (FV) and profunda femoris vein
(PFV) adjacent to the femoral artery before compression (left) and compressed (right)
From the collection of Jeffrey W. Olin; used with permission
There are two well-validated approaches to venous ultrasound of the leg: proximal and whole leg.
• Proximal-leg ultrasound, recommended by UK-based NICE, assesses only the veins above
the calf.[12] Proximal-leg ultrasound is a quick and simple investigation that doesn't require
extensive training and therefore is more readily available than whole-leg ultrasound. However,
it can miss a DVT that doesn't completely occlude the vein, or is situated in the iliac or calf
veins. If the patient is categorised as ‘DVT likely' (Wells ≥2), proximal-leg ultrasound must be
DIAGNOSIS
repeated after 6 to 8 days if the initial scan is negative, to exclude any undetected calf-vein DVTs
that have propagated proximally.[12] Whole-leg ultrasound is recommended by the European
Society of Vascular Surgery if you suspect distal (calf) DVT.[26]
• Whole-leg ultrasound assesses the veins of both the upper leg and calf. It takes longer to
perform, and is technically more demanding, than proximal-leg ultrasound. However, it is
possible to reach a diagnostic conclusion in a single session of whole-leg ultrasound. Some
UK centres advocate repeating the whole-leg ultrasound if the patient has a negative whole-leg
ultrasound, and is categorised as ‘DVT likely’ or has a positive D-dimer. Whole-leg ultrasound
can also identify calf-vein DVT. The usefulness of detecting a calf-vein DVT is debated because
this might resolve without treatment (therefore its detection can lead to over-diagnosis and
potentially over-treatment with anticoagulation, putting the patient at risk of possible bleeding
complications).
• The subsequent rate of VTE following a negative diagnostic evaluation does not appear to
meaningfully differ between whole-leg ultrasound and serial proximal ultrasound.[89]
Colour flow ultrasound is sometimes performed in conjunction with B-mode image

ultrasonography.[27]
• Findings can include reduced or absent spontaneous flow, lack of respiratory variation,
intraluminal echoes, or colour flow patency abnormalities.
• A curvilinear probe may be used to attempt to visualise the iliac veins, but this modality does not
allow for compression.
• The absence of respiratory variations on colour flow ultrasound raises the suspicion of a
proximal venous obstruction.
If a whole-leg ultrasound confirms distal (calf) DVT, check your local protocol for recommendations on
whether and how to start anticoagulation; there is debate in the guidelines.
• In the UK, common practice is to start anticoagulation unless the patient has a high risk of bleeding
or the DVT is not extensive (<5 cm). Seek advice from a haematologist if the patient has a high
bleeding risk or the DVT is not extensive. See Confirmed distal (calf) DVTunderManagement
recommendationsfor more information.

Organise a venous ultrasound, with the result available within 4 hours.[12] [60]
• If the result of a proximal-leg ultrasound is negative, order D-dimer testing.[12] If the result of D-
dimer testing is:[12]
• Positive, organise a repeat venous ultrasound 6 to 8 days later but do not start interim
therapeutic anticoagulation. If this repeat ultrasound is negative, consider alternative
causes[12]
• Negative, consider alternative causes.
• If the result of a whole-leg ultrasound is negative:
• Check your local protocol because recommendations vary
• Some UK centres advocate a repeat ultrasound in this scenario
DIAGNOSIS
• However, the European Society for Vascular Surgery does not recommend a repeat
ultrasound, and advises to consider alternative causes.[26]
If the result of the venous ultrasound is not available within 4 hours:[12]
• Order a D-dimer test and then offer interim therapeutic anticoagulation

• Organise a venous ultrasound with the result available within 24 hours.

If the patient has a positive D-dimer result, organise a venous ultrasound with the result available within 4
hours if possible.[12]
• If the result will not be available within 4 hours, start interim therapeutic anticoagulation and
organise a venous ultrasound with the result available within 24 hours.[12]
• If the result of the venous ultrasound is negative, check your local protocol for advice on next steps
because practice varies. NICE in the UK recommends stopping interim anticoagulation (if this
has been started) and considering other causes.[12] However, some UK centres may consider
21
repeating the ultrasound (even if whole-leg ultrasound has been used) to identify missed distal
(calf) DVT that is extending proximally.
Other investigations
Baseline blood tests

Order the following baseline blood tests before starting anticoagulation:[12] [26]
• Full blood count

• Urea and creatinine
• Liver function tests
• Clotting screen, which should include prothrombin time (PT) and activated partial thromboplastin
time (aPTT).
Do not wait for the results of these baseline blood tests before starting anticoagulation.[12] However,
ensure you have reviewed (and acted on if necessary) the results within 24 hours of starting
anticoagulation.[12]
Further imaging
Consider computed tomography (CT; or magnetic resonance imaging [MRI]) venography if venous
ultrasound is not available or inconclusive.[26] [27] Contrast venography (using x-ray) is now rarely used,
except when other investigations are inconclusive, or catheter-based treatment is considered.[26]
• Note that these recommendations don’t cover pregnant patients - see Suspected DVT in pregnancy
below if your patient is pregnant.
Other indications for CT (or MRI) venography include:
• Detection of more proximal thrombosis if this is clinically suspected or suggested by flow patterns
on Doppler ultrasound[90]
• Detection of other medical conditions that may be an alternative cause of the patient’s symptoms
DIAGNOSIS
and/or increase the risk of DVT, such as extrinsic venous compression syndromes or pelvic
malignancies[26] [27]
• Diagnosis of pulmonary embolism before insertion of filter devices (although this is not required in
practice if anticoagulation has been started)[27]
• Planned endovascular treatment.[27]
CT may also be more accurate than ultrasound at detecting thrombosis in larger veins of the abdomen
and pelvis.[26] [90] However, it requires the use of iodine contrast, and involves radiation exposure (a
significant concern, particularly in younger patients).[26] MRI has shown similar sensitivity and specificity
to venous ultrasound for diagnosis of DVT, but has been evaluated in far fewer studies, using a variety of
different techniques.[27]
Suspected DVT in pregnancy

Consider the diagnosis of DVT in a pregnant patient based on a high index of clinical suspicion, and
ensure close follow-up if DVT is confirmed.[26]
Diagnosis of DVT in pregnant patients is particularly challenging. This is due to several factors, including:
• An overlap of the symptoms and signs associated with pregnancy and thrombosis
• Higher prevalence of iliac vein thrombosis in pregnant patients compared with non-pregnant
patients.[91] Iliac vein thrombosis is difficult to detect using venous ultrasound, particularly if
proximal (rather than whole-leg) ultrasound is used
• A physiological rise in D-dimer level with each trimester. This means that D-dimer plays a limited
role in diagnosis of DVT in pregnant patients[92]
• The Wells score not being validated in pregnant patients.[27] Do not use the Wells score to
risk stratify a pregnant patient with suspected DVT. The LEFt (symptoms in the left leg [L]; calf
circumference difference of cm or over [E for oedema]; presentation in the first trimester [Ft]) score
is an alternative to Wells if there is low pre-test probability (based on clinical findings) of suspected
DVT.[26] [27] However, the LEFt score is not widely used in UK practice; always check your local
protocols and seek advice from a senior colleague if you are unsure of the best approach for your
patient.
Start interim therapeutic anticoagulation (unless contraindicated, and after taking baseline blood tests) if
DVT is suspected while waiting for results from investigations.[26] [27]
Use venous ultrasound as the initial investigation of choice.[26] [27]
• Repeat the venous ultrasound if you have high clinical suspicion of DVT but the initial venous
ultrasound is negative, particularly if you suspect iliac vein thrombosis.[26] [27]
• Additional imaging (such as magnetic resonance imaging venography, or conventional contrast
venography using x-ray) may be considered in some cases by a specialist, but these techniques
may be associated with risks to the foetus.[26] [27]
Interim therapeutic anticoagulation for suspected DVT

Before starting interim therapeutic anticoagulation for suspected DVT, order baseline blood tests including
full blood count, renal and hepatic function, prothrombin time (PT), and activated partial thromboplastin
time (aPTT).[12] [26]
• However, do not wait for the results of these before starting anticoagulation.[12]
• Review the results (and act on these if necessary) within 24 hours of starting anticoagulation.[12]
Practical tip
DIAGNOSIS
dimer result can occur if blood is drawn after the patient has started an anticoagulant.[26]
If possible, choose an interim anticoagulant that can be continued if DVT is

confirmed.[12] See Management recommendations for more information about anticoagulation.
Start interim therapeutic anticoagulation (as long as there are no contraindications) if:[12]
• The patient is categorised as ‘DVT likely’ (Wells score ≥2) and the result of venous ultrasound is not
available within 4 hours
• The patient is categorised as ‘DVT unlikely’ (Wells score <2) and:
• The D-dimer level has been taken but the result is not available within 4 hours
OR
• The D-dimer result is positive, and a venous ultrasound has been arranged with the result
• You suspect DVT clinically in a pregnant patient.[27] Do not wait for the results of imaging.[27]
Stop interim therapeutic anticoagulation if venous ultrasound is negative.[12]
23
Further assessment and investigation of unprovoked DVT

An unprovoked DVT is a DVT in a patient who had no pre-existing, major, transient provoking risk factor in
the prior 3 months.[12]
• Major provoking risk factors include: major surgery; trauma; significant immobility (bedbound,
unable to walk unaided, or likely to spend a substantial proportion of the day in bed or in a chair);
pregnancy or puerperium; use of oral contraceptive/hormone replacement therapy).
An unprovoked DVT may be suggestive of an underlying condition so further investigations are

sometimes warranted.
Undiagnosed cancer
In any patient diagnosed with unprovoked DVT who is not known to have cancer:[12]
• Review medical history

• Review baseline blood tests including full blood count, renal and hepatic function, prothrombin time
(PT), and activated partial thromboplastin time (aPTT)
• Offer a physical examination.[26]
Do not offer further investigations for cancer for patients with an unprovoked DVT unless they have
relevant clinical symptoms or signs.[12] Occult cancer is present in approximately 3% to 5% of patients
with an unprovoked DVT.[93]
These recommendations are from the National Institute for Health and Care Excellence in the UK.
However, note that the European Society for Vascular Surgery recommends clinical examination and
sex-specific cancer screening (but without routine extensive screening for cancer) if the patient has an
unprovoked DVT.[26]
Evidence: Cancer screening
The evidence supporting screening for undiagnosed cancer after unprovoked venous
thromboembolism is inconclusive.
DIAGNOSIS
• A screening strategy that was proposed in the SOMIT trial included pelvic and abdominal
computed tomography combined with mammography and sputum cytology. This was
recommended as the most effective and least harmful approach for patients.
• However, no 5-year survival benefit was found when this approach was compared with basic
clinical evaluation.[94] [95]
Thrombophilia testing
Consider testing for hereditary thrombophilia in patients who don't have an identifiable risk factor
and have a first-degree relative who has had a venous thromboembolism, if it is planned to stop
anticoagulation.[12] [26]
• Do not routinely offer thrombophilia testing to first-degree relatives of people with a history of DVT
and thrombophilia.[12]
• Consider testing for antiphospholipid antibodies in patients who have had an unprovoked DVT if it is
planned to stop anticoagulation treatment.[12] [26] In practice, this is usually only done if the patient
is under 50 years of age.
Practical tip
Be aware that tests for hereditary thrombophilia and antiphospholipid antibodies can be affected by
anticoagulation; specialist advice may be needed.[12]
More info: Thrombophilia
Thrombophilia commonly refers to five hereditary conditions (factor V Leiden, prothrombin

gene 20210A, deficiencies in antithrombin, protein C deficiency, and protein S deficiency) and
antiphospholipid syndrome (an acquired condition). However, many gene variants and acquired
conditions modify thrombosis risk.[96] Antiphospholipid antibodies may predict a higher risk of
future thrombosis following an initial venous thromboembolism event, and may impact selection of
anticoagulant therapy.[40]
Suspected concomitant pulmonary embolism

If the patient has a confirmed DVT, do not routinely investigate for pulmonary embolism (PE) unless the
patient has relevant symptoms or signs.[26]
If the patient has a confirmed proximal DVT, signs or symptoms of PE, and is haemodynamically stable,
further investigation for PE is not needed because the patient will require anticoagulation regardless of
whether they have PE.[27]
If the patient is haemodynamically unstable with signs of right ventricular dysfunction but PE is unable to
be confirmed, diagnosis of a proximal DVT justifies thrombolysis.[27]
See our topic Pulmonary embolism for detailed information regarding diagnosis and management.
History and exam

Key diagnostic factors
calf swelling (common)
DIAGNOSIS
Unilateral leg and thigh swelling can be assessed by measuring the circumference of the leg 10 cm
below the tibial tuberosity. If there is a difference in circumference, DVT is more likely. A difference of
>3 cm between the extremities is a component of the Wells score.[12]
localised pain along deep venous system (common)

Localised pain can be assessed by gently palpating along the path of the deep venous system from
groin to adductor canal and in the popliteal fossa. This is a component of the Wells score.
Significant pain, particularly in combination with marked swelling and cyanosis, is a sign of phlegmasia
cerulea dolens (PCD). If you suspect PCD, start immediate treatment; do not wait for the results
of investigations because this is a life- and limb-threatening emergency.[81] See Phlegmasia
cerulea dolensunder Management recommendations.
presence of risk factors (common)

Ask about significant risk factors, which include:
25
• Active cancer (treatment ongoing, within 6 months, or palliative)[12] [24] [25] [26] [27]
• Recent trauma or fracture[29] [29] [30]
• Paralysis, paresis, or recent plaster immobilisation of the lower extremities[12] [18] [26] [27]
• Hereditary thrombophilia (e.g., factor V Leiden, prothrombin gene G20210A mutation, protein C
or protein S deficiency)
positive Wells score (common)

Assess the clinical probability of DVT using the Wells score (unless the patient is pregnant; see
Suspected DVT in pregnancy under Diagnosis recommendations).[12] [26] [27]
• There are several risk assessment models available to assess the clinical probability of DVT;
however, the Wells score provides a reproducible method to determine the clinical probability of
DVT and is the most widely accepted and validated pretest probability tool used in diagnostic
algorithms for DVT.[26] [85] [86]
The two-level Wells score categorises patients as ‘DVT likely’ (Wells score ≥2) or ‘DVT unlikely’ (Wells
score <2).[12] [26] [27]
• A three-level iteration of the Wells score (where patients are categorised into low, moderate,
or high clinical likelihood of DVT) is available but the two-level score is generally preferred in
practice.[26] [27]
Practical tip
DIAGNOSIS
The Wells score may underestimate the probability of DVT in certain patient groups, such
as patients who misuse intravenous drugs.[87] In practice, categorise patients who inject
drugs into a femoral vein as ‘DVT likely'.
Wells#score elements Score
Active cancer (any treatment within past 6 1

months)
Calf swelling where affected calf 1

circumference measures >3 cm more than
the other calf (measured 10 cm below tibial
tuberosity)
Prominent superficial veins (non-varicose) 1
Pitting oedema (confined to symptomatic 1

leg)
Swelling of entire leg 1
Localised pain along distribution of deep 1

venous system
Paralysis, paresis, or recent cast 1

immobilisation of lower extremities
Recent bed rest for >3 days or major 1

surgery requiring regional or general
anaesthetic within past 12 weeks
Previous history of DVT or pulmonary 1

embolism
Alternative diagnosis at least as probable 1
DIAGNOSIS
*Two versions of the risk assessment model have been validated: two categories (DVT unlikely
or likely) or three categories (low, intermediate, or high clinical probability. The simplified version
(producing two score categories) is presented as it is likely the easiest to use in clinical settings.
Use the Wells score in combination with a diagnostic algorithm.[12] [26] [27] See Diagnostic
algorithmunder Diagnosis recommendations for more information. The National Health Institute for
Health and Care Excellence (UK) recommends the following:[12]
• If the patient is categorised as ‘DVT likely’, organise a venous ultrasound, with the result
available within 4 hours.[12] [60] Start therapeutic anticoagulation if proximal DVT is
confirmed[12]
• If the patient is categorised as ‘DVT unlikely’, order a D-dimer with the result available within 4
hours[12]
See Investigations for next steps, or if the results of investigations aren’t available within 4 hours.
27
If a whole-leg ultrasound confirms distal (calf) DVT, check your local protocol for advice on whether
and how to start anticoagulation; guidelines vary in terms of their recommendations. In the UK,
common practice is to start anticoagulation unless the patient has a high risk of bleeding or the DVT is
not extensive (<5 cm).
redness and warmth (uncommon)

Symptoms of DVT.[83]
coolness (uncommon)
A symptom of DVT.
Other diagnostic factors

asymmetric oedema (common)
Presence of oedema worse on leg with suspected DVT.
prominent superficial veins (common)

Dilated superficial veins over foot and leg (not varicose veins) are a sign of DVT.
swelling of the entire leg (uncommon)

Increases pretest probability of diagnosis of DVT. A difference of >3 cm between the extremities is a
component of the Wells score.[12]
Marked swelling, particularly in combination with significant pain and cyanosis, is a sign of phlegmasia
cerulea dolens (PCD). If you suspect PCD, start immediate treatment; do not wait for the results
of investigations because this is a life- and limb-threatening emergency.[81] See Phlegmasia
cerulea dolensunder Management recommendations.
cyanosis (uncommon)
Cyanosis (blue discoloration), particularly in combination with marked swelling and significant pain,
DIAGNOSIS
is a sign of phlegmasia cerulea dolens (PCD). If you suspect PCD, start immediate treatment; do not
wait for the results of investigations because this is a life- and limb-threatening emergency.[81]
See Phlegmasia cerulea dolensunder Management recommendations.
Investigations
1st test to order
Test Result
quantitative D-dimer level normal (DVT excluded if Wells
Suitability of D-dimer testing depends on:[12] [26] [27] score <2); elevated (proceed
to imaging)
• Whether the patient’s Wells score has categorised the patient
as ‘DVT likely’ (Wells ≥2) or ‘DVT unlikely’ (Wells <2)
AND
• The availability of venous ultrasound.
If the patient is pregnant, do not use D-dimer testing (or the Wells
score) to confirm or rule out DVT.[26] [27] See Suspected DVT in
pregnancy under Diagnosis recommendations for more information.
If D-dimer testing is indicated, consider:[12]
• Fully quantitative point-of-care D-dimer testing if laboratory

facilities are not available (e.g., in a primary care setting)
• An age-adjusted D-dimer test threshold if the patient is aged
over 50 years.
Practical tip
If D-dimer testing is required, always order this before giving

anticoagulation; a false negative D-dimer result can occur if
blood is drawn after giving anticoagulation.[26]
DIAGNOSIS
Venous ultrasound is the first-line investigation for patients deemed
‘DVT likely’.[12] [26] [27] See Venous ultrasound below. However,
request D-dimer testing if the result of venous ultrasound is:[12]
• Negative
OR
• Not available within 4 hours. After the D-dimer test, start
interim therapeutic anticoagulation, and organise a venous
ultrasound with the result available within 24 hours.[12]

Request D-dimer testing for all patients categorised as ‘DVT
unlikely’.[12] [26] [27]
• If the D-dimer level has been taken but the result is

not available within 4 hours, start interim therapeutic
• If the D-dimer level is elevated, organise:[12]
29
Test Result
• A venous ultrasound, with the result available within 4
hours
OR
• Interim therapeutic anticoagulation, and a venous
ultrasound with the result available within 24 hours.
• A normal D-dimer level excludes the diagnosis of DVT;

consider alternative causes.[12]
Practical tip
Be aware that an elevated D-dimer level is non-specific and is

frequently abnormal in patients without DVT who are older, are
acutely ill, have underlying hepatic disease, have an infection,
or are pregnant.
venous ultrasound abnormal B-mode image:

Venous ultrasonography is the first-line method of imaging.[12] [26] inability to fully compress
lumen of vein using
Choose to use venous ultrasound based on whether the patient’s
Wells score has categorised them as ‘DVT likely’ or ‘DVT unlikely’, ultrasound transducer; normal
and the result of D-dimer testing (if this is indicated).[12] A positive B-mode image: all vein
venous ultrasound confirms the diagnosis of DVT.[12] [26] [27] segments fully compressible,
non-diagnostic
In the UK, different centres may use either proximal or whole-leg
venous ultrasound. Check your local protocol to determine the abnormal Doppler: reduced
recommended strategy. or absent spontaneous flow,
lack of respiratory variation,
• The UK National Institute for Health and Care Excellence
(NICE) recommends using proximal venous ultrasound intraluminal echoes, or colour
only.[12] However, the European Society of Vascular Surgery flow patency abnormalities
DIAGNOSIS
recommends whole-leg ultrasound if you suspect distal (calf)

DVT.[26] Both strategies have advantages and disadvantages.
If a whole-leg ultrasound confirms distal (calf) DVT, check your

local protocol for recommendations on whether and how to start
anticoagulation; there is debate in the guidelines.
• In the UK, common practice is to start anticoagulation

unless the patient has a high risk of bleeding or the DVT is
not extensive (<5 cm). Seek advice from a haematologist
if the patient has a high bleeding risk or the DVT is not
extensive. See Confirmed distal (calf) DVT under Management
recommendations for more information.

Organise a venous ultrasound, with the result available within 4
hours.[12] [60]
Test Result
• If the result of a proximal-leg ultrasound is negative, order D-
dimer testing.[12] If the result of D-dimer testing is:[12]
• Positive, organise a repeat venous ultrasound 6

to 8 days later but do not start interim therapeutic
anticoagulation. If this repeat ultrasound is negative,
consider alternative causes[12]
• Negative, consider alternative causes.
• If the result of a whole-leg ultrasound is negative:
• Check your local protocol because recommendations

vary; some UK centres advocate a repeat ultrasound in
this scenario
• However, the European Society for Vascular Surgery
does not recommend a repeat ultrasound, and advises
to consider alternative causes.[26]
If the result of the venous ultrasound is not available within 4

hours:[12]
• Order a D-dimer test and then offer interim therapeutic

anticoagulation
• Organise a venous ultrasound with the result available within
24 hours.

If the patient has a positive D-dimer result, organise a venous
ultrasound with the result available within 4 hours if possible.[12]
DIAGNOSIS
• If the result will not be available within 4 hours, start interim
therapeutic anticoagulation and organise a venous ultrasound
with the result available within 24 hours.[12]
• If the result of the venous ultrasound is negative, check your
local protocol for advice on next steps because practice varies
in the UK. NICE in the UK recommends stopping interim
anticoagulation (if this has been started) and considering
other causes.[12] However, some UK centres may consider
repeating the ultrasound (even if whole-leg ultrasound has
been used) to look for missed distal (calf) DVT that is extending
proximally.
full blood count baseline levels

Order as a baseline level before starting anticoagulation.[12] [26] Do
not wait for the result before starting anticoagulation.[12] However,
ensure you have reviewed (and acted on if necessary) the results
within 24 hours of starting anticoagulation.[12]
31
Test Result
A component of the assessment of bleeding risk while using
anticoagulation. For example, marked thrombocytopaenia or severe
anaemia can be contraindications to anticoagulation.
May detect abnormalities such as underlying haematological

malignancy (e.g., anaemia, leucopenia).
A high platelet count may suggest essential thrombocytosis or a

myeloproliferative disorder. Exceedingly low platelet count may
preclude the use of some anticoagulants. Heparin therapy can be
associated with heparin-induced thrombocytopenia; platelet counts
should be measured at baseline and regularly throughout treatment.
urea and creatinine baseline levels

Doses of some anticoagulants (e.g., low molecular weight heparin,

fondaparinux, apixaban, rivaroxaban, dabigatran, edoxaban) may
need to be adjusted or discontinued in patients with renal impairment,
so baseline values should be obtained.
liver function tests baseline levels
• Note that choice of anticoagulant for a patient with hepatic

DIAGNOSIS
impairment depends on the underlying cause and severity of

hepatic impairment.
May detect abnormalities associated with underlying provoking factor

(e.g., cancer).
clot ting screen baseline levels
Order a clotting screen, which should include prothrombin time (PT)
and activated partial thromboplastin time (aPTT), as a baseline
level before starting anticoagulation.[12] [26] Do not wait for the
result before starting anticoagulation.[12] However, ensure you have
reviewed (and acted on if necessary) the results within 24 hours of
starting anticoagulation.[12]
Other tests to consider
Test Result
CT/MRI venography presence of an intraluminal
Note that these recommendations do not apply to pregnant patients - filling defect
see Suspected DVT in pregnancy under Diagnosis recommendations
if your patient is pregnant.
Consider CT (or MRI) venography if venous ultrasound is not

available or inconclusive.[26] [27] Contrast venography (using x-ray)
is now rarely used, except when other investigations are inconclusive,
or catheter-based treatment is considered.[26]
Other indications for CT (or MRI) venography include:
• Detection of more proximal thrombosis if this is clinically

suspected or suggested by flow patterns on Doppler
ultrasound[90]
• Detection of other medical conditions that may be an
alternative cause of the patient’s symptoms and/or increase the
risk of DVT, such as extrinsic venous compression syndromes
or pelvic malignancies[26] [27]
• Diagnosis of pulmonary embolism before insertion of
filter devices (although this is not required in practice if
anticoagulation has been started)[27]
• Planned endovascular treatment.[27]
CT may also be more accurate than ultrasound at detecting

thrombosis in larger veins of the abdomen and pelvis.[26] [90]
However, it requires the use of iodine contrast, and involves
radiation exposure (a significant concern, particularly in younger
patients).[26] MRI has shown similar sensitivity and specificity to
venous ultrasound for diagnosis of DVT, but has been evaluated in far
fewer studies, using a variety of different techniques.[27]
DIAGNOSIS
further investigation for unprovoked DVT may show underlying cause
An unprovoked DVT is a DVT in a patient who had no pre-existing,
major, transient provoking risk factor in the prior 3 months.[12]
• Major provoking risk factors include: major surgery; trauma;

significant immobility (bedbound, unable to walk unaided, or
likely to spend a substantial proportion of the day in bed or in
a chair); pregnancy or puerperium; use of oral contraceptive/
hormone replacement therapy).
An unprovoked DVT may be suggestive of an underlying condition so

further investigations are sometimes warranted.
Undiagnosed cancer
In any patient diagnosed with unprovoked DVT who is not known to
have cancer:[12]
33
Test Result
• Review baseline blood tests including full blood count, renal
and hepatic function, prothrombin time (PT), and activated
partial thromboplastin time (aPTT)
Do not offer further investigations for cancer for patients with an

unprovoked DVT unless they have relevant clinical symptoms or
signs.[12] Occult cancer is present in approximately 3% to 5% of
patients with an unprovoked DVT.[93]
These recommendations are from the National Institute for Health

and Care Excellence in the UK. However, note that the European
Society for Vascular Surgery recommends clinical examination
and sex-specific cancer screening (but without routine extensive
screening for cancer) if the patient has an unprovoked DVT.[26]
Thrombophilia testing
Consider testing for hereditary thrombophilia in patients who don't
have an identifiable risk factor and have a first-degree relative who
has had a VTE, if it is planned to stop anticoagulation.[12] [26]
• Do not routinely offer thrombophilia testing to first-

degree relatives of people with a history of DVT and
thrombophilia.[12]
• Consider testing for antiphospholipid antibodies in patients
who have had an unprovoked DVT if it is planned to stop
anticoagulation treatment.[12] [26] In practice, this is usually
only done if the patient is under 50 years of age.
Practical tip
Be aware that tests for hereditary thrombophilia and

antiphospholipid antibodies can be affected by anticoagulation;
DIAGNOSIS
specialist advice may be needed.[12]
Differentials
Condition Differentiating signs / Differentiating tests

symptoms
Cellulitis • Patients with cellulitis usually • Leukocytosis is common,
present with redness, heat, with a WBC count >10 × 10⁹/
and swelling in the dermis L (10,000 cells/microlitre).
of the affected leg. The • Fluid collection seen if
affected area is likely to be abscess present.
smaller than in DVT (which • Ultrasound differentiates
may involve the entire foot, diagnoses.
calf, or thigh), but the signs
more pronounced.
• The demarcation of the skin
margins affected by cellulitis
is more defined than in DVT.
• Portal of infection entry may
be identified.[97]
• Fever and prior history of
cellulitis is common.
• May occur with a concurrent
DVT.
Calf muscle tear/Achilles' • History of trauma or sudden • No DVT seen on MRI or

tendon tear onset of calf pain. ultrasound.
• Muscle tear is difficult to • Oedema associated with
differentiate from DVT on muscle tear makes it very
examination. Although defect difficult to visualise the calf
or spasm of calf muscles is veins using ultrasonography.
noted on examination, calf Furthermore, extreme
DVT may occasionally be tenderness associated
associated with spasm. with a muscle tear makes it
difficult to compress with the
ultrasound probe.
DIAGNOSIS
Calf muscle haematoma • Calf injury or sudden onset • Venous ultrasound shows no
of calf pain. There may be thrombosis, and there may
ecchymosis on the skin. be ultrasound evidence of a
• Calf haematoma, calf muscle haematoma.
tear, and calf muscle tendon
tear frequently occur in the
absence of injury or trauma.
Large or ruptured • Sudden onset of calf pain. • Ultrasound shows fluid in

popliteal cyst (Baker's • Tenderness in popliteal the soft tissues of the calf or
cyst) fossa. visualises cyst.
Pelvic/thigh mass/tumour • Oedema usually occurs • Venous ultrasound, CT scan,

compressing venous without pain in venous outlet or MRI of abdomen, pelvis,
out flow from the leg obstruction. and thigh with contrast,
• Difficult to distinguish from may show obstructing mass
iliac or caval DVT (which impinging on the femoral,
may co-exist). iliac, or vena cava vessels.
35
Criteria
Wells score
• Active cancer (treatment ongoing, within 6 months, or palliative): 1 point
• Calf swelling where affected calf circumference measures >3 cm more than the asymptomatic calf
(measured 10 cm below tibial tuberosity): 1 point
• Collateral superficial veins (non-varicose): 1 point
• Pitting oedema (confined to symptomatic leg): 1 point
• Swelling of entire leg: 1 point
• Localised pain along distribution of deep venous system: 1 point
• Paralysis, paresis, or recent plaster immobilisation of lower extremities: 1 point
• Recent bed rest for ≥3 days, or major surgery requiring regional or general anaesthetic within past 12
weeks: 1 point
• Previous history of DVT or pulmonary embolism: 1 point
• Alternative diagnosis at least as likely as DVT: subtract 2 points.
If the Wells score is ≥2, the patient is classified as ‘DVT likely' (absolute risk is approximately 40%).[85] [86] If
the Wells score is <2 the patient is classified as ‘DVT unlikely’ (probability <15%).[12] [85] [86]
Ultrasonography criteria
The radiologist or technician who performs lower-extremity ultrasound first locates the femoral artery and
vein in the groin region. The artery and its associated pulsatility can be identified readily; the femoral vein is
adjacent. Inability to compress the vein indicates the presence of a clot, but provides no information on the
age of the clot.[98]
All of the deep veins in the leg must be identified and compressed in a deliberate and systematic fashion
(including the deep veins of the calf if whole-leg ultrasound is chosen). There must be a careful search for a
duplicated femoral vein and a duplicated popliteal vein.
DIAGNOSIS
Secondary criteria include a larger vein diameter on the affected side, and absent or scant echoes within the
clot. In acute DVT, the vein is non-compressible and dilated. In subacute DVT, the vein is non-compressible
and marginally dilated or of normal size. In chronic DVT, the affected vein is non-compressible and small.
Acute DVT is frequently easy to determine on the ultrasound, but where the vein is normal-sized or the vein
is partially compressible or partially non-compressible, it is more difficult to determine the age of the DVT. In
these cases, the DVT is referred to as age-indeterminant.
Warkentin Probability Scale for heparin-induced thrombocytopenia

(HIT)[99]
The Warkentin Probability Scale for HIT (the '4T score') can be used to estimate the probability of a patient
having HIT. Points are scored (0, 1, or 2) for each of the 4 categories (maximum possible score = 8).
Thrombocytopenia
• 2 points if >50% fall in platelet count to a platelet count nadir of ≥20 × 10⁹/L (≥20,000/mm³ or 20 × 10³/
microL)
• 1 point if 30% to 50% fall in platelet count, or if the nadir is 10-19 × 10⁹/L (10-19,000/mm³ or 10-19 ×
10³/microL)
• 0 points if <30% fall in the platelet count, or if the nadir is <10 × 10⁹/L (<10,000/mm³ or 10 × 10³/
microL).
Timing* of onset of platelet fall (or other sequelae of HIT)
• 2 points if onset is 5 to 10 days after starting heparin, or <1 day if there has been recent heparin
(within past 30 days)
• 1 point if onset is more than 10 days after starting heparin or if timing unclear; or if <day 1 after starting
heparin with recent heparin (past 31-100 days)
• 0 points if onset is within 4 days of first time heparin exposure (no recent heparin).
Thrombosis or other sequelae
• 2 points if there is a proven new thrombosis, or skin necrosis, or acute systemic reaction after
intravenous unfractionated heparin bolus
• 1 point if there is progressive or recurrent thrombosis, or erythematous skin lesions, or suspected
thrombosis (not proven)
• 0 points if no thrombosis or other finding.
Other cause(s) of platelet fall
• 2 points if none evident

• 1 point if there is another possible cause
• 0 points if there is another definite cause.
Pretest probability score
• High = 6 to 8 points (probability of HIT approximately 50%)

• Intermediate = 4 to 5 points (probability of HIT approximately 10%)
DIAGNOSIS
• Low = 0 to 3 points (<1% probability of HIT).
*First day of immunising heparin exposure is considered day 0.
Screening
Ultrasound screening
Compression ultrasound looking for evidence of acute DVT is an excellent screening test in high-risk
patients, such as patients who have sustained major trauma and patients who have recently undergone total
hip or knee replacement. There is no convincing evidence, however, that screening reduces the incidence of
adverse outcomes, particularly the incidence of fatal pulmonary embolism. The overall accuracy of screening
ultrasound in asymptomatic patients is not clear but it is lower than in symptomatic patients.[100] Less than
half of patients who develop pulmonary embolism have ultrasound evidence of DVT in the legs; therefore,
the value of detecting asymptomatic DVT in preventing pulmonary embolism is uncertain. Guidelines conflict
regarding whether screening ultrasound should be performed in hospitalised trauma patients.[101] [102]
37
Thrombophilia screening
Consider testing for hereditary thrombophilia in patients who don't have an identifiable risk factor and have a
first-degree relative who has had a VTE, if it is planned to stop anticoagulation.[12] [26]
• Do not routinely offer thrombophilia testing to first-degree relatives of people with a history of DVT and
thrombophilia.[12]
• Consider testing for antiphospholipid antibodies in patients who have had an unprovoked DVT if it is
planned to stop anticoagulation treatment.[12] [26] In practice, this is usually only done if the patient is
young (aged <50 years).
Be aware that tests for hereditary thrombophilia and antiphospholipid antibodies can be affected by
anticoagulation; specialist advice may be needed.[12]
Cancer screening
In any patient diagnosed with unprovoked DVT who is not known to have cancer:[12]

• Review baseline blood tests including full blood count, renal and hepatic function, prothrombin time
(PT), and activated partial thromboplastin time (aPTT)
Do not offer further investigations for cancer for patients with an unprovoked DVT unless they have relevant
clinical symptoms or signs.[12] Occult cancer is present in approximately 3% to 5% of patients with an
unprovoked DVT.[93]
These recommendations are based on the National Institute for Health and Care Excellence in the UK.
However, note that the European Society for Vascular Surgery recommends clinical examination and
sex-specific cancer screening (but without routine extensive screening for cancer) if the patient has an
unprovoked DVT.[26]
DIAGNOSIS
Deep vein thrombosis Management
Recommendations
Key Recommendations
If the patient has a confirmed proximal DVT, start anticoagulation (unless contraindicated).[12] [26] [27]
• Base your choice of anticoagulant on the patient’s comorbidities and contraindications as well as
taking account of local guidelines. Consult a haematologist if a patient has a contraindication to
anticoagulation.
• Apixaban or rivaroxaban are first-line if there are no special considerations; low

molecular weight heparin followed by dabigatran or edoxaban or overlapped with warfarin is
an alternative if apixaban or rivaroxaban are unsuitable.[12] [26]
• Be aware of special patient groups, including pregnant patients; those with active cancer,
renal impairment, or hepatic impairment; and patients at extremes of body weight. These
groups will need a tailored approach to anticoagulant therapy.[12] Check your local protocols
and consider seeking advice from a haematologist, particularly if the patient has triple-
positive antiphospholipid syndrome.
• Give anticoagulation for at least 3 months.[12] Longer-term, or sometimes indefinite,

anticoagulation may be needed for secondary prevention after weighing the individual patient’s risk
of recurrence versus bleeding risk.[12]
If you suspect phlegmasia cerulea dolens (PCD), act quickly because PCD is a life- and limb-
threatening emergency; do not wait for the results of investigations to start treatment.[26] Immediately
start anticoagulation, refer the patient to a vascular surgeon, elevate the affected limb, and seek advice
from critical care.
If the patient has a confirmed distal (calf) DVT, check your local protocol for advice on whether and how to
start anticoagulation; guidelines vary in terms of their recommendations. In the UK, common practice is to
start anticoagulation unless the patient has a high risk of bleeding or the DVT is not extensive (<5 cm).
Advise early mobilisation and consider compression stockings to manage acute symptoms.[26] [27]
Most patients with DVT can be safely discharged and managed at home.[27]
Full Recommendations
Set ting of care
Most patients with suspected or confirmed DVT can receive treatment at home, rather than in the
hospital.[27] Outcomes are at least as good as those achieved with hospitalisation, and improved patient
satisfaction.[103] However, arrange hospital admission if any of the following apply:
• Suspected or confirmed concomitant pulmonary embolism (PE) requiring admission (e.g.,

MANAGEMENT
haemodynamically unstable, intermediate-risk PE based on the Pulmonary Embolism Severity

Index [PESI] score or the simplified Pulmonary Embolism Severity Index [sPESI] score).[12] [104]
See our topic Pulmonary embolism for more information on criteria for admission for a patient with
concomitant PE
39
• Highly symptomatic DVT (e.g., severe pain and oedema in the presence of acute DVT requiring
inpatient analgesia), or phlegmasia cerulea dolens
• The patient needs support with ongoing anticoagulation therapy that cannot be adequately
arranged in the outpatient or emergency department setting
• Co-existing comorbidity requiring hospital management
• DVT that is best treated with intravenous unfractionated heparin.
In practice, most patients with risk factors for bleeding that require close observation (e.g., chronic
liver disease with or without varices, recent or prior gastrointestinal bleeding, chronic renal stones with
recurrent haematuria, bleeding disorder, malignancy, recent stroke, or prior intracranial haemorrhage) can
be managed at home unless they are actively bleeding. Seek advice from a senior colleague if you are
unsure.
Phlegmasia cerulea dolens

If you suspect phlegmasia cerulea dolens (PCD), act quickly because PCD is a life- and limb-
threatening emergency; do not wait for the results of investigations to start treatment.[26] Immediately:
• Start anticoagulation with either low molecular weight heparin or unfractionated heparin[26]
• Refer the patient to a vascular surgeon
• Treatment options include catheter-directed thrombolysis, pharmacomechanical-directed

thrombolysis, and surgical thrombectomy (which may be combined with fasciotomy and iliac
stenting), although these are generally used for PCD due to iliac vein DVT[26] [105] [106]
[107] [108] [109]
• Elevate the affected leg[26]

• Seek urgent advice from the critical care team about appropriate resuscitation measures.
Suspected DVT: interim therapeutic anticoagulation

Before starting interim therapeutic anticoagulation for suspected DVT, order baseline blood tests
including full blood count, renal and hepatic function, prothrombin time (PT), and activated partial
thromboplastin time (aPTT).[12] [26]
• However, do not wait for the results of these before starting anticoagulation.[12]
• Review the results (and act on these if necessary) within 24 hours of starting anticoagulation.[12]
Practical tip
dimer result can occur if blood is drawn after the patient has been given anticoagulation.[26]
If possible, choose an interim anticoagulant that can be continued if DVT is confirmed.[12] See Confirmed

MANAGEMENT
proximal DVT: initiation phase of anticoagulation (up to 10 days following diagnosis) below for more
information about anticoagulation.
Start interim therapeutic anticoagulation (as long as there are no contraindications) if:[12]
• The patient is categorised as ‘DVT likely’ (Wells score ≥2) and the result of venous ultrasound is not
• The patient is categorised as ‘DVT unlikely’ (Wells score <2) and:
• The D-dimer level has been taken but the result is not available within 4 hours
OR
• The D-dimer result is positive, and a venous ultrasound has been arranged with the result
• You suspect DVT clinically in a pregnant patient.[27] Do not wait for the results of imaging.[27]
Stop interim therapeutic anticoagulation if venous ultrasound is negative.[12]
Confirmed proximal DVT: initiation phase of

anticoagulation (up to 10 days following diagnosis)
The initiation phase covers the period up to 10 days following diagnosis of DVT.[26]
Give anticoagulation (unless contraindicated) to all patients if they have a proximal DVT.[12] [26] [27] The
National Health Institute for Health and Care Excellence (NICE) in the UK recommends that patients with
proximal DVT of the leg should receive anticoagulation for at least 3 months.[12]
• Note that a separate initiation phase may only be required if the patient is receiving warfarin,
because warfarin requires a loading period. In UK practice, direct oral anticoagulants (DOACs)
are more widely used than warfarin; therefore, the initiation and treatment phases are usually
combined, spanning the period from diagnosis to 3 months.
• The aim of the initiation phase is to stop the active prothrombotic state and to inhibit thrombus
propagation and embolisation.
• Anticoagulation is the mainstay of therapy for the treatment of DVT and can:
• Prevent propagation/progression of the thrombus in the deep veins in the legs

• Reduce the risk of pulmonary embolism
• Reduce the risk of recurrent DVT.
Base your choice of anticoagulant on the patient’s comorbidities and contraindications as well as taking
account of local guidelines.
Consult a haematologist if the patient has a contraindication to anticoagulation. See Patients with a
contraindication to anticoagulation below.
MANAGEMENT
41
More info: DOACs
• The DOACs rivaroxaban, apixaban, edoxaban, and dabigatran are as effective as unfractionated
heparin (UFH), low molecular weight heparin (LMWH), and warfarin for the treatment of
DVT, and are generally recommended over warfarin, UFH, and LMWH outside of special
populations.[12] [110] No monitoring of coagulation profile is necessary, and bleeding
complications are similar to those of warfarin, but there is a lower or similar incidence of major
bleeding with pulmonary embolism. All have a longer half-life than UFH or LMWH and a shorter
half-life than warfarin, and all have a rapid onset of action.
• Unlike warfarin, DOACs do not interact with food. However, rivaroxaban at doses ≥15 mg/day
should be given with the largest meal of the day (most often the evening meal) to maximise
absorption.
• DOACs do, however, have some drug-drug interactions. Notable drug interactions include:
strong P-glycoprotein inducers and inhibitors (dabigatran and edoxaban); strong inhibitors or
inducers of P-glycoprotein and CYP3A4 (apixaban and rivaroxaban).
• Specific reversal agents for dabigatran (idarucizumab) and the oral factor Xa inhibitors
apixaban and rivaroxaban (recombinant coagulation factor Xa [andexanet alfa]) have
been approved in the UK. Note that andexanet alfa is only approved for life-threatening or
uncontrolled gastrointestinal bleeding in England. Reversal of warfarin, in the setting of
major or life-threatening bleeding, is recommended with vitamin K and prothrombin complex
concentrates.[111]
• Dabigatran and edoxaban require lead-in therapy with a parenteral anticoagulant such as UFH
or LMWH for 5 to 10 days.
• Rivaroxaban and apixaban are initiated at a higher initial dose (for 7-21 days) with no need for
lead-in therapy with a parenteral anticoagulant.
• Argatroban (a thrombin inhibitor) or danaparoid may be used if the patient has suspected or
confirmed heparin-induced thrombocytopenia (HIT).[26] Bivalirudin, desirudin, and fondaparinux
have also been suggested, but are not licensed for active HIT in the UK.[26] [IHI: anticoagulant
toolkit – reducing adverse drug events]
MANAGEMENT
More info: Warfarin
• Start warfarin within 24 hours of diagnosis and ensure overlap with parenteral anticoagulation
for at least 5 days or until the international normalised ratio (INR) is ≥2 for at least 24 hours
(whichever is longer).[12] Subsequent dosing of warfarin is based on the INR response to each
dose. The therapeutic INR range is 2 to 3 (target 2.5, unless concomitantly being used for
anticoagulation of mechanical heart valves).
• Three strategies can be used to select the initial dose of warfarin: a clinical algorithm calculates
the estimated stable and starting dose based on several patient characteristics; a genetic
algorithm calculates the estimated stable and starting dose based on the results of genetic
tests such as CYP450-2C9 genotype and VKOR-C1 haplotype, as well as clinical variables; a
fixed-dose approach uses initiation nomograms based on starting doses of 5 mg/day or 10 mg/
day.[112] [113]
• Use of an individualised nomogram for selecting the initial warfarin dose, and for subsequent
titrations, is likely to result in better outcomes than a fixed-dose initiation, and is preferred.[113]
[114] Tests are available that determine the genotype of the patient for cytochrome 2C9 variants
and vitamin K epoxide reductase variants. However, overall, this information has not led to more
rapid or safe anticoagulation compared with routine dosing. Genotyping is expensive and it
takes several days to receive results.[115] [116] [117] [118]
• If available, take an individualised approach to warfarin initiation. Use an online tool to assist
with warfarin initiation dosing that utilises clinical variables with or without the addition of genetic
information. [Warfarin dosing]
More info: Unfractionated heparin, low molecular weight heparin, and fondaparinux
• Unfractionated heparin (UFH) treatment is usually initiated with an intravenous weight-based

loading bolus followed immediately by initiation of a weight-based continuous infusion. It also
requires monitoring of activated partial thromboplastin time or heparin-calibrated anti-Xa activity,
which is used to titrate dosing to the target range.
• Low molecular weight heparin (LMWH) and fondaparinux are dosed subcutaneously, according
to patient weight.
• Platelet count is measured prior to, and regularly during, treatment with any heparin (e.g.,
UFH, LMWH) therapy because of the possibility of heparin-induced thrombocytopenia as a
complication.
Confirmed proximal DVT

See Confirmed proximal DVT: special patient groups below if the patient is pregnant; has active cancer,
renal impairment, or hepatic impairment; or is at extremes of body weight.
For all other patients with confirmed proximal DVT, start anticoagulation as soon as possible with
MANAGEMENT
apixaban or rivaroxaban (these are examples of DOACs); low molecular weight heparin (LMWH) is an
alternative if these are unsuitable.[12] [26]
• Use argatroban (a thrombin inhibitor) or danaparoid if the patient has suspected or confirmed
heparin-induced thrombocytopaenia (HIT).[26] Bivalirudin, desirudin, and fondaparinux have
43
also been suggested as suitable options, but are not licensed for active HIT in the UK.[26] [IHI:
anticoagulant toolkit – reducing adverse drug events] See the Complications section for more
information.
If using rivaroxaban or apixaban, note that these drugs may be started without the need for lead-in
therapy with a parenteral anticoagulant first.[12]
• Acute-phase treatment consists of an increased dose of the oral anticoagulant over the first 3
weeks (for rivaroxaban), or over the first 7 days (for apixaban).[27]
If using LMWH, continue treatment for at least 5 days.[12]
• If ongoing anticoagulation will be with edoxaban or dabigatran, note that at least 5 days of lead-in
therapy with LMWH is required first
OR
• If ongoing anticoagulation will be with warfarin, start warfarin within 24 hours of diagnosis and
ensure overlap with LMWH for at least 5 days or until the international normalised ratio (INR) is ≥2
for at least 24 hours (whichever is longer).[12]
Practical tip
Never give a DOAC simultaneously with parenteral anticoagulation.

• While warfarin is started at the same time as a parenteral anticoagulant and overlapped for at
least 5 days or until the INR is ≥2 for at least 24 hours (whichever is longer), DOACs should
never be overlapped or given at the same time as a parenteral anticoagulant.
• Apixaban and rivaroxaban may be started without the need for lead-in therapy with a parenteral
anticoagulant first.
• However, dabigatran and edoxaban require at least 5 days lead-in therapy with a parenteral
anticoagulant before starting treatment. The parenteral anticoagulant should be stopped before
dabigatran or edoxaban are started.
Confirmed proximal DVT: special patient groups

Be aware of special patient groups, including pregnant patients; those with active cancer, renal
impairment, or hepatic impairment; and patients at extremes of body weight. These groups will need a
tailored approach to anticoagulant therapy.[12] Check your local protocols and consider seeking advice
from a haematologist, particularly if the patient has triple-positive antiphospholipid syndrome (although
this is unlikely to be known before anticoagulants are started).
Pregnancy
Use a weight-adjusted dose of LMWH in patients who are pregnant because LMWH does not cross the
placenta.[26]
MANAGEMENT
• Do not routinely measure peak anti-Xa activity in patients who are pregnant (or in the postnatal
period), except in patients who weigh <50 kg or ≥90 kg or those with renal impairment.[26]
Do not give DOACs or a vitamin K antagonist (VKA; e.g., warfarin) during pregnancy as they may
cross the placenta.[26] Never give a DOAC if the patient is breasfeeding.[26] Warfarin appears to be safe
to use in breastfeeding but in practice it may not be preferred (over LMWH) by the patient because it
requires regular monitoring of INR.
Active cancer
Check local protocols for these patients. UK-based NICE recommends using a DOAC first-line.[12] Take
into account the tumour site, the patient’s bleeding risk, and interactions with other drugs, including those
being used to treat the cancer.[12] If a DOAC is unsuitable, NICE recommends using either:[12]
• LMWH alone
OR
• LMWH overlapped with a VKA; warfarin is the most commonly used VKA in practice. Ensure
overlap of the two drugs for at least 5 days or until the INR is ≥2 in two consecutive readings
followed by a VKA on its own.
• Note that warfarin is rarely used in UK practice for a patient with active cancer.
Renal impairment
Seek advice from a haematologist for these patients. NICE in the UK recommends the following approach
based on estimated creatinine clearance (CrCl).[12]
• For patients with CrCl 15-50 mL/minute, offer one of:
• Apixaban (use caution if CrCl is 15-29 mL/minute)

• Rivaroxaban (use caution if CrCl is 15-29 mL/minute)
• LMWH or UFH, which can be overlapped with a VKA (warfarin is the most commonly used
VKA in practice); overlap for at least 5 days or until the INR is at least 2.0 in 2 consecutive
readings, followed by a VKA on its own) or used as lead-in therapy before starting edoxaban.
LMWH or UFH can also be used as lead-in therapy before starting dabigatran if CrCl is ≥30
mL/minute.
• For patients with CrCl <15 mL/minute offer one of:
• LMWH or UFH, which can be overlapped with a VKA (warfarin is the most commonly used
VKA in practice). Ensure overlap of the two drugs for at least 5 days or until the INR is ≥2 in
two consecutive readings followed by a VKA on its own
• LMWH alone
• UFH alone.
MANAGEMENT
Check your local drug formulary for any monitoring requirements or dose adjustments in renal
impairment, particularly if CrCl is <15 mL/minute.[12]
45
Practical tip
Warfarin is safe to use in patients with renal impairment with no dose adjustments necessary.
However, monitor the INR more carefully in these patients.
Hepatic impairment
Note that choice of anticoagulant for a patient with hepatic impairment depends on the underlying cause
and severity of hepatic impairment.
• In practice, patients may have acute, mild hepatic impairment (e.g., secondary to intercurrent
illness) and, once their hepatic impairment has resolved, they may be treated with a DOAC.
• DOACs are generally not recommended in patients with moderate to severe chronic liver disease
(Child-Pugh class B or C).[27] However, apixaban may be used in selected patients, and LMWH
or UFH are also options. In practice, overlap both LMWH and UFH with warfarin, unless cancer
is present. Use warfarin with caution if the patient’s baseline INR is elevated; extended-duration
LMWH may be preferred.[119]
NICE in the UK doesn’t give specific recommendations for patients with hepatic impairment.
Check your local drug formulary for any dose adjustments in hepatic impairment.
Extremes of body weight

Check your local protocols and consider seeking advice from a haematologist or a multdisciplinary team
before choosing the most appropriate anticoagulant for these patients.[12]
• In UK practice, a DOAC may be used if the patient weighs up to 120 kg, and rivaroxaban or
apixaban may be used if the patient weighs >120 kg.[120]
• However, NICE recommends using an anticoagulant with monitoring of therapeutic levels (e.g.,
warfarin) if the patient weighs <50 kg or >120 kg, and checking any required dose adjustments.[12]
Practical tip
Drug-drug interactions may increase the risk of bleeding in patients receiving anticoagulation,
particularly when anticoagulation is combined with antiplatelet therapy.[121] In practice, aspirin is
generally stopped while the patient is receiving anticoagulation, unless there is a strong indication
to continue it. Seek advice if in doubt. Both the pharmacodynamic (e.g., non-steroidal anti-
inflammatory drugs, selective serotonin-reuptake inhibitors) and pharmacokinetic (e.g., amiodarone,
rifampicin) interactions should be thoroughly evaluated prior to initiation of anticoagulation. In
particular, commonly overlooked interactions include those between a DOAC and phenytoin,
carbamazepine, and HIV protease inhibitors.
Confirmed proximal DVT: treatment phase of

anticoagulation (initiation to 3 months)
MANAGEMENT
Continue anticoagulation for a minimum of 3 months.[12] [27] During this time, follow-up and re-
evaluation are based on the patient’s level of risk for bleeding, comorbidities, and the anticoagulant
selected.
• In UK practice, because direct oral anticoagulants (DOACs) are more widely used than warfarin,
the initiation and treatment phases are usually combined, spanning the period from diagnosis to
3 months. A separate initiation phase may only be required if the patient is receiving warfarin,
because warfarin requires a loading period.
• The aim of the treatment phase is to prevent new thrombus while the original clot is stabilised and
intrinsic thrombolysis is under way.
DOACs
If the patient is taking dabigatran or edoxaban, continue the same dose started in the initiation phase for
at least 3 months.[27]
• However, if the patient’s renal function declines significantly, the DOAC should be
discontinued.[27] In practice, switch to an alternative anticoagulant (unless the patient has a very
low-risk DVT [e.g., small distal DVT]).
If the patient is taking apixaban or rivaroxaban, adjust the dose after the initiation phase (at 7 days for
apixaban, and 21 days for rivaroxaban).[27]
Warfarin
Monitor the patient’s international normalised ratio (INR). The frequency of measurements depends on
the stability of INR values.
• In practice, measure INR every 3 to 4 days during initial dose titration if the patient is being
managed as an outpatient, with the time between measurements progressively extending if values
remain in range. However, if the patient is in hospital, consider measuring INR daily, particularly if
they are acutely unwell.
• Maintain a target range of 2 to 3 (target INR 2.5), unless anticoagulation is also being used for a
separate indication that requires a higher target INR.[27]
Low molecular weight heparin (LMWH)

If extended LMWH is used, the dosing strategy is agent-specific; check your local protocol and seek
advice from a pharmacist/haematologist if you are unsure.
Adjust the LMWH dose to any change in the patient’s weight or creatinine clearance.
Confirmed proximal DVT: extended phase of

anticoagulation (3 months to indefinite)
Bear in mind that not all patients will need continued anticoagulation beyond 3 months. The aim of the
extended phase is secondary prevention of new venous thromboembolism. See the Prevention section for
other methods of secondary prevention aside from anticoagulation.
MANAGEMENT
Duration
Discuss with a senior colleague whether to continue anticoagulation beyond 3 months if the patient
has a first presentation of proximal DVT. This decision should assess the individual patient’s risk of
recurrence of DVT versus bleeding risk, as well as considering whether the DVT was provoked or
47
unprovoked.[12] Discuss the risks and benefits of long-term anticoagulation with the patient, and take
their preferences into account.[12]
• A provoked DVT is a DVT associated with a major transient risk factor that was present in the 3
months prior to the DVT.[12]
• An unprovoked DVT is a DVT in a patient who had no pre-existing, major, transient, provoking risk
factor in the prior 3 months.[12]
• Major provoking risk factors include: major surgery; trauma; significant immobility (bedbound,
unable to walk unaided, or likely to spend a substantial proportion of the day in bed or in a chair);
pregnancy or puerperium; use of oral contraceptive/hormone replacement therapy.[12]
In general, anticoagulation can usually be stopped after 3 months (or 3-6 months for people with active
cancer) if the DVT was provoked, as long as the major transient risk factor is no longer present and the
clinical course has been uncomplicated.[12]
• In the UK, some centres may continue anticoagulation beyond 3 months for patients with a minor
transient risk factor (e.g., minor surgery).
Anticoagulation is usually continued for longer than 3 months if the DVT was unprovoked.[12]
• In practice, patients with persisting risk factors (e.g., active cancer, autoimmune conditions such as
systemic lupus erythematosus and inflammatory bowel disease) usually continue anticoagulation
long-term, unless they had a major provoking risk factor (e.g., major surgery).
• If the patient has active cancer, anticoagulation is continued for at least 6 months.[12] In practice,
this will be for at least the duration of cancer treatment, or until remission is achieved.
Annually reassess the risks/benefits of continuing anticoagulation, as well as the patient's general health
and treatment preferences, in all patients receiving extended treatment beyond 3 months.[12] [60]
Choice of anticoagulant
In general, offer continued treatment with the anticoagulant used in the acute phase if it is well
tolerated.[12]
• If the patient has been started on a direct oral anticoagulant other than apixaban and this is not
well tolerated, or the clinical situation or patient preference has changed, the National Institute
for Health and Care Excellence in the UK recommends to consider switching to apixaban if the
patient does not have renal impairment, active cancer, established triple-positive antiphospholipid
syndrome, or extreme body weight (<50 kg or >120 kg).[12] However, in practice, many patients
may prefer an alternative anticoagulant that can be taken as a once-daily regimen.
• In patients taking apixaban who need ongoing anticoagulation for >6 months, consider a dose
reduction.[122] In UK practice, if the patient is taking rivaroxaban in this scenario, a dose reduction
may be considered if there is concern about the risk of bleeding.
• In pregnant patients, continue low molecular weight heparin for the remainder of the pregnancy and
MANAGEMENT
for at least 6 weeks postnatally and until at least 3 months of treatment has been given in total.[123]
Consider aspirin if the patient declines or is unable to tolerate any form of oral anticoagulant.[12]
More info: Anticoagulation for unprovoked DVT
Many studies have attempted to identify subgroups of patients with unprovoked venous
thromboembolism (VTE) who do not need to be treated indefinitely with oral anticoagulation. There
is strong evidence that the risk of recurrent VTE is higher in the following patients: male sex; those
with a diagnosis of a proximal DVT (versus isolated distal [calf] DVT); those with ultrasound evidence
of residual clot; those who have an elevated D-dimer 1 month after stopping a 3- to 6-month course
of oral anticoagulation; and those who had an unprovoked DVT.[27] [124] [125] [126] [127] Several
risk assessment models have been developed for this purpose, including the DASH score, the Vienna
Prediction Model, and the 'Men Continue and HER-DOO2' model.[128] The latter model identifies a
subset of women with low risk for recurrent VTE after an initial unprovoked event, and a prospective
validation study of this model has been published.[129] However, these models are not widely used in
practice.
Confirmed distal (calf) DVT

If a whole-leg ultrasound confirms distal (calf) DVT, check your local protocol for advice on whether and
how to start anticoagulation; guidelines vary in terms of their recommendations.
• In the UK, common practice is to:
• Start anticoagulation unless the patient has a high risk of bleeding or the DVT is not
extensive (<5 cm)
• Seek advice from a haematologist if the patient has a high bleeding risk or the DVT is not
extensive.
• The European Society for Vascular Surgery recommends considering anticoagulation based on the
patient’s symptoms, risk factors for extension, and bleeding risk.[26]
• Note that the National Institute for Health and Care Excellence in the UK does not give
recommendations for distal (calf) DVT.[12]
If anticoagulation is suitable, use the same regimens as for proximal DVT.[130] Take into account the
patient’s comorbidities, contraindications, and your local guidelines. See Confirmed proximal DVT:
initiation phase of anticoagulation (up to 10 days following diagnosis) above for information about starting
anticoagulation.
If anticoagulation is not suitable, or contraindicated, check your local protocol to determine further
management. The European Society for Vascular Surgery recommends arranging clinical reassessment
and repeat whole-leg ultrasound after 1 week.[26]
Risk factors for extension include:[130]
• Positive D-dimer
• Extensive DVT (e.g., >5 cm long)
MANAGEMENT
• DVT involving multiple veins

• DVT >7 mm in maximum diameter (however, in practice this measurement is not routinely reported)
• DVT close to the proximal veins
• Absence of any reversible provoking factor
• Active cancer
49
• Past history of venous thromboembolism
• Patient being managed in hospital.
Compression stockings and physical activity

Consider using compression stockings to manage leg symptoms such as pain, oedema, and residual
venous obstruction.[12] [26]
• The National Institute for Health and Care Excellence in the UK does not recommend using
compression stockings to prevent post-thrombotic syndrome.[12] This is debated in the literature;
consult your local protocol.[131]
• Explain to the patient how to use the stockings, how long they should be worn, and when they
should be replaced.[12]
Advise early mobilisation and walking exercise to relieve symptoms of acute DVT.[27] Some sources
suggest that this light physical activity may also help to reduce the risk of post-thrombotic syndrome.[132]
[133] [134] [135]
Patients with a contraindication to anticoagulation

Consult a haematologist if the patient has a contraindication to anticoagulation.
• Many patients with relative contraindications will still be able to have a different choice or altered
dose of anticoagulation, but a specialist opinion is needed to weigh up the benefit-risk balance.
• Absolute contraindications are rare but include:[136]
• Active bleeding
• Recent intracranial haemorrhage
• Recent, planned, or emergent surgery or procedure with high bleeding risk
• Platelet count <50,000/uL
• Severe bleeding diathesis.
• Relative contraindications include:[136]
• Recurrent but inactive gastrointestinal bleeding

• Intracranial or spinal tumour
• Recent, planned, or emergent surgery or procedure with intermediate bleeding risk
• Major trauma including cardiopulmonary resuscitation
• Aortic dissection.
• Remember, too, that each anticoagulant may have its own specific relative and absolute
contraindications (e.g., heparin is contraindicated in patients with a history of heparin-induced
thrombocytopenia) and these should be checked before starting treatment.
MANAGEMENT
Practical tip
• Peptic ulcer disease with no history of bleeding or faecal occult blood is not a contraindication to
• Anticoagulation is safe in most trauma and neurosurgical patients after the first or second
postoperative week and in most stroke patients without haemorrhage.[136]
• Patients with spinal cord injury without haematomyelia may still be considered for
Consider a retrievable inferior vena cava (IVC) filter for any patient with confirmed proximal DVT who is
deemed unsuitable for anticoagulation after discussion with a haematologist.[12] [26] [27] The aim of an
IVC filter is to prevent embolisation to pulmonary embolism.[26]
• Presence of an IVC filter is associated with a doubling of the long-term risk of recurrent lower-
extremity DVT.
• If the contraindication to anticoagulation has resolved, assess the patient for initiation of
anticoagulation and removal of the IVC filter.[27]
Practical tip
Always document the plan for IVC filter removal at the time it is inserted. Forgotten IVC filters can
lead to significant long-term complications.
Recurrent VTE despite adequate anticoagulation therapy

Seek advice from haematology for any patient who has a recurrent venous thromboembolism (VTE)
despite adequate anticoagulation treatment. Recurrent VTE is unusual among patients receiving
therapeutic-dose anticoagulant therapy, except in those with active cancer (7% to 9% on-therapy
recurrence with low‐molecular‐weight heparin).[13] [137] [138]
• Check adherence to anticoagulation treatment.[12]

• Address other sources of hypercoagulability (e.g., underlying malignancy).[12]
• Consider other reasons for reduced efficacy of anticoagulation (e.g., rivaroxaban not being taken
with food).[139]
In the absence of any of the above issues, options include:[12]
• Increasing the dose of anticoagulant

• Changing to a different anticoagulant with a different mode of action.
Patients with recurrent VTE despite treatment with adequate anticoagulation can be considered for an
inferior vena cava filter.[12]
Note that these recommendations are based on the National Institute for Health and Care Excellence
MANAGEMENT
guideline in the UK, which covers patients with proximal DVT only. In UK practice, some experts
may apply these recommendations equally to patients with distal (calf) DVT in the absence of
recommendations from guidelines. Seek advice from a specialist if needed.
51
Treatment algorithm overview

Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
Initial ( summary )
suspected DVT of the leg
with phlegmasia cerulea 1st anticoagulation

dolens
plus immediate referral to a vascular surgeon
plus supportive care
without phlegmasia 1st consider interim anticoagulation

cerulea dolens
plus decide on set ting of care
Acute ( summary )
initiation-phase therapy: confirmed
proximal DVT of the leg
no contraindication to 1st anticoagulation

anticoagulation: non-
pregnant
plus physical activity
consider compression stockings
no contraindication 1st low molecular weight heparin

to anticoagulation:
pregnant
contraindication to 1st consider anticoagulation OR an IVC filter

anticoagulation
initiation phase therapy: confirmed

distal DVT of the leg
MANAGEMENT
1st repeat imaging of the deep veins OR

anticoagulation
Ongoing ( summary )
treatment-phase therapy: confirmed
DVT of the leg
1st maintain anticoagulation
extended-phase therapy: confirmed

DVT of the leg
1st consider extended anticoagulation
recurrent venous thromboembolism
1st increase dose of anticoagulant OR switch

to alternative anticoagulant
consider IVC filter
MANAGEMENT
53
Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
Initial
suspected DVT of the leg
with phlegmasia cerulea 1st anticoagulation

dolens
Primary options
» heparin: 75 mg/kg intravenously as a

loading dose, followed by 18 units/kg/hour
intravenous infusion, adjust dose according
to aPTT; 5000 units intravenously as a
loading dose, followed by 15,000 units
subcutaneously every 12 hours, adjust dose
according to aPTT
OR
» enoxaparin: 1 mg/kg subcutaneously every

12 hours
OR
» dalteparin: 100 units/kg subcutaneously

every 12 hours, maximum 18,000 units/dose
» If you suspect phlegmasia cerulea dolens

(PCD), act quickly because PCD is a life-
and limb-threatening emergency; do not
wait for the results of investigations to start
treatment.[26]
» Immediately start anticoagulation with either

unfractionated heparin or a low molecular weight
heparin such as enoxaparin or dalteparin.[26]
plus immediate referral to a vascular surgeon
Treatment recommended for ALL patients in
selected patient group
» Refer the patient immediately to a vascular
surgeon.
• Treatment options include

catheter-directed thrombolysis,
pharmacomechanical-directed
thrombolysis, and surgical thrombectomy
MANAGEMENT
(which may be combined with fasciotomy

and iliac stenting), although these are
generally used for phlegmasia cerulea
Initial
dolens due to iliac vein DVT.[105] [106]
[107]
plus supportive care

» Elevate the affected leg and seek urgent
advice from the critical care team about
appropriate resuscitation measures.[26]
without phlegmasia 1st consider interim anticoagulation
cerulea dolens
» Before starting interim therapeutic
anticoagulation for suspected DVT, order
baseline blood tests including full blood count,
renal and hepatic function, prothrombin time,
and activated partial thromboplastin time.[12]
[26]
• However, do not wait for the results of

these before starting anticoagulation.[12]
• Review the results (and act on these if
necessary) within 24 hours of starting
Practical tip
If D-dimer testing is required, always order

this before giving anticoagulation; a false
negative D-dimer result can occur if blood
is drawn after the patient has been given
» If possible, choose an interim

anticoagulant that can be continued if DVT is
confirmed.[12] See the No contraindication to
anticoagulationtreatments under Initiation-phase
therapy: confirmed proximal DVT of the leg below
for more information about anticoagulation.
» Start interim therapeutic anticoagulation (as

long as there are no contraindications) if:[12]
• The patient is categorised as ‘DVT

likely’ (Wells score ≥2) and the result of
venous ultrasound is not available within 4
hours
• The patient is categorised as ‘DVT
MANAGEMENT
unlikely’ (Wells score <2) and:
• The D-dimer level has been taken

but the result is not available within
4 hours
55
Initial
OR
• The D-dimer result is positive, and
a venous ultrasound has been
arranged with the result available
within 24 hours
• You suspect DVT clinically in a pregnant

patient.[27] Do not wait for the results of
imaging.[27]
» Stop interim therapeutic anticoagulation if

venous ultrasound is negative.[12]
plus decide on set ting of care

» Most patients with suspected or confirmed
DVT can receive treatment at home, rather
than in the hospital.[27] Outcomes are at least
as good as those achieved with hospitalisation,
and improved patient satisfaction.[103]
However, arrange hospital admission if any of
the following apply:
• DVT that is best treated with intravenous

unfractionated heparin
• Suspected or confirmed concomitant
pulmonary embolism (PE) requiring
admission (e.g., haemodynamically
unstable, intermediate-risk PE based
on the Pulmonary Embolism Severity
Index [PESI] score or the simplified
Pulmonary Embolism Severity Index
[sPESI] score)[12] [104] See our topic
Pulmonary embolism for more information
on criteria for admission for a patient with
concomitant PE
• Highly symptomatic DVT (e.g., severe
pain and oedema in the presence of acute
DVT requiring inpatient analgesia), or
phlegmasia cerulea dolens
• The patient needs support with ongoing
anticoagulation therapy that cannot be
adequately arranged in the outpatient or
emergency department setting
MANAGEMENT
• Co-existing comorbidity requiring hospital

management.
» In practice, most patients with risk factors for

bleeding that require close observation (e.g.,
chronic liver disease with or without varices,
Initial
recent or prior gastrointestinal bleeding, chronic
renal stones with recurrent haematuria, bleeding
disorder, malignancy, recent stroke, or prior
intracranial haemorrhage) can be managed at
home unless they are actively bleeding. Seek
advice from a senior colleague if you are unsure.
MANAGEMENT
57
Acute
initiation-phase therapy: confirmed
proximal DVT of the leg
no contraindication to 1st anticoagulation

anticoagulation: non-
Primary options
pregnant
No special considerations; active cancer
» apixaban: 10 mg orally twice daily for 7
days, followed by 5 mg twice daily
OR

» rivaroxaban: 15 mg orally twice daily for 21
days, followed by 20 mg once daily
OR
Active cancer
» edoxaban: start following initial use of a
parenteral anticoagulant for at least 5 days;
body weight ≤60 kg: 30 mg orally once daily;
body weight >60 kg: 60 mg orally once daily
OR
Active cancer
» dabigatran: start following initial use of a
18-74 years of age: 150 mg orally twice daily;
75-79 years of age: 110-150 mg orally twice
daily; ≥80 years of age: 110 mg orally twice
daily
Secondary options
No special considerations
OR
MANAGEMENT

daily
OR
Acute
» enoxaparin: uncomplicated patients
with low risk of recurrence: 1.5 mg/kg
subcutaneously every 24 hours; patients with
risk factors: 1 mg/kg subcutaneously every 12
hours
-or-
» dalteparin: patients with increased risk of
bleeding: 100 units/kg subcutaneously every
12 hours; patients with no increased risk of
bleeding: 200 units/kg subcutaneously every
24 hours, maximum 18,000 units/dose
--AND--
» warfarin: 5-10 mg orally once daily initially,
adjust dose according to target INR
Starting dose can be calculated
using an online tool that takes patient
characteristics and/or CYP2C9/VKORC1
genotype information (if available)
into account. Warfarin dosing http://
www.warfarindosing.org/Source/Home.aspx
OR
Active cancer
12 hours
OR
Active cancer
once daily for the first 30 days, followed
by 150 units/kg once daily for 5 months,
maximum 18,000 units/dose
Refer to local drug formulary for a table of
recommended weight-based doses. Use
fixed-dose syringes for this indication.
OR
Active cancer
12 hours
-or-
MANAGEMENT

--AND--
59
Acute
» The initiation phase covers the period up to 10

days following diagnosis of DVT.[26]
» Give anticoagulation (unless contraindicated)

to all patients if they have a proximal DVT.[12]
[26] [27] The National Health Institute for
Health and Care Excellence (NICE) in the UK
recommends that patients with proximal DVT
of the leg should receive anticoagulation for at
least 3 months.[12]
• Note that a separate initiation phase may

only be required if the patient is receiving
warfarin, because warfarin requires a
loading period. In UK practice, direct
oral anticoagulants (DOACs) are more
widely used than warfarin; therefore,
the initiation and treatment phases are
usually combined, spanning the period
from diagnosis to 3 months.
• The aim of the initiation phase is to
stop the active prothrombotic state and
to inhibit thrombus propagation and
embolisation.
• Anticoagulation is the mainstay of therapy
for the treatment of DVT and can:
• Prevent propagation/progression of
the thrombus in the deep veins in
the legs
• Reduce the risk of pulmonary
embolism
• Reduce the risk of recurrent DVT.
» Base your choice of anticoagulant on the

patient’s comorbidities and contraindications as
MANAGEMENT
well as taking account of local guidelines.
» If the patient has active cancer, renal

impairment, or hepatic impairment, or is at
extremes of body weight, see Confirmed
proximal DVT: special patient groups below.
Acute
» For all other patients with confirmed proximal
DVT, start anticoagulation as soon as possible
with apixaban or rivaroxaban (these
are examples of DOACs); a low molecular
weight heparin (LMWH) such as enoxaparin
or dalteparin is an alternative if these are
unsuitable.[12] [26]
» If using rivaroxaban or apixaban, note that

these drugs may be started without the need for
lead-in therapy with a parenteral anticoagulant
first.[12]
• Acute-phase treatment consists of an

increased dose of the oral anticoagulant
over the first 3 weeks (for rivaroxaban), or
over the first 7 days (for apixaban).[27]
» If using LMWH, continue treatment for at least

5 days.[12]
• If ongoing anticoagulation will be with

edoxaban or dabigatran, note that at least
5 days of lead-in therapy with LMWH is
required first
OR
• If ongoing anticoagulation will be with
warfarin, start warfarin within 24 hours of
diagnosis and ensure overlap with LMWH
for at least 5 days or until the international
normalised ratio (INR) is ≥2 for at least 24
hours (whichever is longer).[12]
MANAGEMENT
61
Acute
Practical tip
Never give a DOAC simultaneously with

parenteral anticoagulation.
• While warfarin is started at the same
time as a parenteral anticoagulant
and overlapped for at least 5 days
or until the INR is ≥2 for at least 24
hours (whichever is longer), DOACs
should never be overlapped or given
at the same time as a parenteral
anticoagulant.
• Apixaban and rivaroxaban may be
started without the need for lead-in
therapy with a parenteral anticoagulant
first.
• However, dabigatran and edoxaban
require at least 5 days lead-in therapy
with a parenteral anticoagulant before
starting treatment. The parenteral
anticoagulant should be stopped before
dabigatran or edoxaban are started.
Confirmed proximal DVT:

special patient groups
Be aware of special patient groups, including
those with active cancer, renal impairment, or
hepatic impairment, and patients at extremes of
body weight. These groups will need a tailored
approach to anticoagulant therapy.[12] Check
your local protocols and consider seeking advice
from a haematologist, particularly if the patient
has triple-positive antiphospholipid syndrome
(although this is unlikely to be known before
anticoagulants are started).
Active cancer
Check local protocols for these patients. UK-
based NICE recommends using a DOAC first-
line.[12] Take into account the tumour site, the
patient’s bleeding risk, and interactions with
other drugs, including those being used to treat
the cancer.[12] If a DOAC is unsuitable, NICE
MANAGEMENT
recommends using either:[12]
• LMWH alone
OR
Acute
• LMWH overlapped with a vitamin K
antagonist (VKA); warfarin is the most
commonly used VKA in practice. Ensure
overlap of the two drugs for at least 5 days
or until the INR is ≥2 in two consecutive
readings followed by a VKA on its own.
• Note that warfarin is rarely used in

UK practice for a patient with active
cancer.
Renal impairment
Seek advice from a haematologist for these
patients. NICE in the UK recommends the
following approach based on estimated
creatinine clearance (CrCl).[12]
• For patients with CrCl 15-50 mL/minute,

offer one of:
• Apixaban (use caution if CrCl is

15-29 mL/minute)
• Rivaroxaban (use caution if CrCl is
15-29 mL/minute)
• LMWH or unfractionated heparin
(UFH), which can be overlapped
with a VKA (warfarin is the most
commonly used VKA in practice);
overlap for at least 5 days or
until the INR is at least 2.0 in 2
consecutive readings, followed by a
VKA on its own) or used as lead-in
therapy before starting edoxaban.
LMWH or UFH can also be used
as lead-in therapy before starting
dabigatran if CrCl is ≥30 mL/minute.
• For patients with CrCl <15 mL/minute offer

one of:
MANAGEMENT
• LMWH or UFH, which can be

overlapped with a VKA (warfarin
is the most commonly used VKA
in practice). Ensure overlap of the
two drugs for at least 5 days or until
63
Acute
the INR is ≥2 in two consecutive
readings followed by a VKA on its
own
• LMWH alone
• UFH alone.
Check your local drug formulary for any

monitoring requirements or dose adjustments in
renal impairment, particularly if CrCl is <15 mL/
minute.[12]
Practical tip
Warfarin is safe to use in patients with

renal impairment with no dose adjustments
necessary. However, monitor the INR more
carefully in these patients.
Hepatic impairment
Note that choice of anticoagulant for a patient
with hepatic impairment depends on the
underlying cause and severity of hepatic
impairment.
• In practice, patients may have acute, mild

hepatic impairment (e.g., secondary to
intercurrent illness) and, once their hepatic
impairment has resolved, they may be
treated with a DOAC.
• DOACs are generally not recommended in
patients with moderate to severe chronic
liver disease (Child-Pugh class B or
C).[27] However, apixaban may be used
in selected patients, and LMWH or UFH
are also options. In practice, overlap both
LMWH and UFH with warfarin, unless
cancer is present. Use warfarin with
caution if the patient’s baseline INR is
elevated; extended-duration LMWH may
be preferred.[119]
NICE in the UK doesn’t give specific

recommendations for patients with hepatic
MANAGEMENT
impairment.
Check your local drug formulary for any dose

adjustments in hepatic impairment.
Acute
Extremes of body weight
Check your local protocols and consider seeking
advice from a haematologist or a multdisciplinary
team before choosing the most appropriate
anticoagulant for these patients.[12]
• In UK practice, a DOAC may be used

if the patient weighs up to 120 kg, and
rivaroxaban or apixaban may be used if
the patient weighs >120 kg.[120]
• However, NICE recommends using
an anticoagulant with monitoring of
therapeutic levels (e.g., warfarin) if
the patient weighs <50 kg or >120
kg, and checking any required dose
adjustments.[12]
Practical tip
Drug-drug interactions may increase

the risk of bleeding in patients receiving
anticoagulation, particularly when
anticoagulation is combined with
antiplatelet therapy.[121] In practice,
aspirin is generally stopped while the
patient is receiving anticoagulation, unless
there is a strong indication to continue
it. Seek advice if in doubt. Both the
pharmacodynamic (e.g., non-steroidal anti-
inflammatory drugs, selective serotonin-
reuptake inhibitors) and pharmacokinetic
(e.g., amiodarone, rifampicin) interactions
should be thoroughly evaluated prior
to initiation. In particular, commonly
overlooked interactions include those
between a DOAC and phenytoin,
carbamazepine, and HIV protease
inhibitors.

» Advise early mobilisation and walking exercise
to relieve symptoms of acute DVT.[27] Some
sources suggest that this light physical activity
may also help to reduce the risk of post-
thrombotic syndrome.[132] [133] [134] [135]
MANAGEMENT

Treatment recommended for SOME patients in
65
Acute
» Consider using compression stockings to
manage leg symptoms such as pain, oedema,
and residual venous obstruction.[12] [26]
• The National Institute for Health and Care

Excellence in the UK does not recommend
using compression stockings to prevent
post-thrombotic syndrome.[12] This is
debated in the literature; consult your local
protocol.[131]
• Explain to the patient how to use the
stockings, how long they should be worn,
and when they should be replaced.[12]
no contraindication 1st low molecular weight heparin

to anticoagulation:
Primary options
pregnant
» enoxaparin: body weight <50 kg: 40 mg
subcutaneously twice daily; body weight
50-69 kg: 60 mg subcutaneously twice daily;
body weight 70-89 kg: 80 mg subcutaneously
twice daily; body weight ≥90 kg: 100 mg
subcutaneously twice daily
Dose based on early pregnancy body weight.
OR
» dalteparin: body weight <50 kg: 5000 units

50-69 kg: 6000 units subcutaneously twice
daily; body weight 70-89 kg: 8000 units
subcutaneously twice daily; body weight ≥90
kg: 10,000 units subcutaneously twice daily
» The initiation phase covers the period up to 10

days following diagnosis of DVT.[26]
» Give anticoagulation (unless contraindicated)

to all patients if they have a proximal DVT.[12]
[26] [27] The National Health Institute for Health
and Care Excellence in the UK recommends
that patients with proximal DVT of the leg
should receive anticoagulation for at least 3
months.[12]
• The aim of the initiation phase is to

stop the active prothrombotic state and
to inhibit thrombus propagation and
MANAGEMENT
embolisation.
» Base your choice of anticoagulant on the

patient’s comorbidities and contraindications as
well as taking account of local guidelines.
Acute
» Use a weight-adjusted dose of a low molecular
weight heparin (LMWH) in patients who are
pregnant because LMWH does not cross the
placenta.[26]
• Do not routinely measure peak anti-Xa

activity in patients who are pregnant (or
in the postnatal period), except in patients
who weigh <50 kg or ≥90 kg or those with
renal impairment.[26]
» Do not give a direct oral anticoagulant

(DOAC) or vitamin K antagonist (e.g.,
warfarin) during pregnancy as they may cross
the placenta.[26] Never give a DOAC if the
patient is breasfeeding.[26] Warfarin appears to
be safe to use in breastfeeding but in practice
it may not be preferred (over LMWH) by the
patient because it requires regular monitoring of
international normalised ratio (INR).

protocol.[131]
contraindication to 1st consider anticoagulation OR an IVC filter

anticoagulation
MANAGEMENT
» The initiation phase covers the period up to

10 days following diagnosis of DVT.[26] The aim
of this phase is to stop the active prothrombotic
state and to inhibit thrombus propagation and
embolisation.
67
Acute
» Consult a haematologist if the patient has a
contraindication to anticoagulation.
• Many patients with relative

contraindications will still be able to have
a different choice or altered dose of
anticoagulation, but a specialist opinion
is needed to weigh up the benefit-risk
balance.
• Absolute contraindications are rare but
include:[136]
• Active bleeding
• Recent intracranial haemorrhage
• Recent, planned, or emergent
surgery or procedure with high
bleeding risk
• Platelet count <50,000/uL
• Severe bleeding diathesis.
• Relative contraindications include:[136]
• Recurrent but inactive

gastrointestinal bleeding
• Intracranial or spinal tumour
• Recent, planned, or emergent
surgery or procedure with
intermediate bleeding risk
• Major trauma including
cardiopulmonary resuscitation
• Aortic dissection.
• Remember, too, that each anticoagulant

may have its own specific relative and
absolute contraindications (e.g., heparin is
contraindicated in patients with a history
of heparin-induced thrombocytopenia) and
these should be checked before starting
treatment.
MANAGEMENT
Acute
Practical tip
• Peptic ulcer disease with no history of

bleeding or faecal occult blood is not a
contraindication to anticoagulation.[136]
• Anticoagulation is safe in most trauma
and neurosurgical patients after the
first or second postoperative week
and in most stroke patients without
haemorrhage.[136]
• Patients with spinal cord injury without
haematomyelia may still be considered
for anticoagulation.[136]
» Consider a retrievable inferior vena cava (IVC)

filter for any patient with confirmed proximal DVT
who is deemed unsuitable for anticoagulation
after discussion with a haematologist.[12]
[26] [27] The aim of an IVC filter is to prevent
embolisation to pulmonary embolism.[26]
• Presence of an IVC filter is associated

with a doubling of the long-term risk of
recurrent lower-extremity DVT.
• If the contraindication to anticoagulation
has resolved, assess the patient for
initiation of anticoagulation and removal of
the IVC filter.[27]
Practical tip
Always document the plan for IVC filter

removal at the time it is inserted. Forgotten
IVC filters can lead to significant long-term
complications.
MANAGEMENT

69
Acute
protocol.[131]
initiation phase therapy: confirmed

distal DVT of the leg
1st repeat imaging of the deep veins OR

anticoagulation
» The initiation phase covers the period up to

10 days following diagnosis of DVT.[26] The aim
of this phase is to stop the active prothrombotic
state and to inhibit thrombus propagation and
embolisation.
» If a whole-leg ultrasound confirms distal

(calf) DVT, check your local protocol
for advice on whether and how to start
anticoagulation; guidelines vary in terms of their
recommendations.
• In the UK, common practice is to:
• Start anticoagulation unless the

patient has a high risk of bleeding
or the DVT is not extensive (<5 cm)
• Seek advice from a haematologist if
the patient has a high bleeding risk
or the DVT is not extensive.
• The European Society for Vascular

Surgery recommends considering
anticoagulation based on the patient’s
symptoms, risk factors for extension, and
bleeding risk.[26]
• Note that the National Institute for Health
and Care Excellence in the UK does not
give recommendations for distal (calf)
DVT.[12]
» If anticoagulation is suitable, use the

same regimens as for proximal DVT (see No
MANAGEMENT
contraindication to anticoagulation: pregnant

under Initiation-phase therapy: confirmed
proximal DVT of the leg above).[130] Take
into account the patient’s comorbidities,
contraindications, and your local guidelines.
Acute
» If anticoagulation is not suitable, or
contraindicated, check your local protocol to
determine further management. The European
Society for Vascular Surgery recommends
arranging clinical reassessment and repeat
whole leg ultrasound after 1 week.[26]
» Risk factors for extension include:[130]
• Positive D-dimer
• Extensive DVT (e.g., >5 cm long)
• DVT involving multiple veins
• DVT >7 mm in maximum diameter
(however, in practice this measurement is
not routinely reported)
• DVT close to the proximal veins
• Absence of any reversible provoking factor
• Active cancer
• Past history of venous thromboembolism
• Patient being managed in hospital.


protocol.[131]
MANAGEMENT
71
Ongoing
treatment-phase therapy: confirmed
DVT of the leg
1st maintain anticoagulation
» The treatment phase covers the period from

initiation to 3 months following diagnosis
of DVT.[26] The aim of the treatment phase is
to prevent new thrombus while the original clot
is stabilised and intrinsic thrombolysis is under
way.
• In UK practice, because direct oral

anticoagulants (DOACs) are more widely
used than warfarin, the initiation and
treatment phases are usually combined,
spanning the period from diagnosis to 3
months. A separate initiation phase may
only be required if the patient is receiving
warfarin, because warfarin requires a
loading period.
• The aim of the treatment phase is to
prevent new thrombus while the original
clot is stabilised and intrinsic thrombolysis
is under way.
DOACs
If the patient is taking dabigatran or edoxaban,
continue the same dose started in the initiation
phase for at least 3 months.[27]
• However, if the patient’s renal function

declines significantly, the DOAC should
be discontinued.[27] In practice, switch
to an alternative anticoagulant (unless
the patient has a very low-risk DVT [e.g.,
small distal DVT]).
If the patient is taking apixaban or rivaroxaban,

adjust the dose after the initiation phase
(at 7 days for apixaban, and 21 days for
rivaroxaban).[27]
Warfarin
MANAGEMENT
Monitor the patient’s international normalised

ratio (INR). The frequency of measurements
depends on the stability of INR values.
Ongoing
• In practice, measure INR every 3 to 4
days during initial dose titration if the
patient is being managed as an outpatient,
with the time between measurements
progressively extending if values remain
in range. However, if the patient is in
hospital, consider measuring INR daily,
particularly if they are acutely unwell.
• Maintain a target range of 2 to 3 (target
INR 2.5), unless anticoagulation is also
being used for a separate indication that
requires a higher target INR.[27]
Low molecular weight heparin

(LMWH)
If extended LMWH is used, the dosing strategy
is agent-specific; check your local protocol and
seek advice from a pharmacist/haematologist
if you are unsure. Adjust the LMWH dose to
any change in the patient’s weight or creatinine
clearance.
See the No contraindication to anticoagulation

treatments under Initiation-phase therapy:
confirmed proximal DVT of the leg above for
more information about anticoagulation.

MANAGEMENT

protocol.[131]
73
Ongoing
extended-phase therapy: confirmed

DVT of the leg
1st consider extended anticoagulation

Primary options
» apixaban: continue 5 mg orally twice daily;
decrease dose to 2.5 mg twice daily after
completing at least 6 months of treatment
OR

» rivaroxaban: continue 20 mg orally once
daily; decrease dose to 10 mg once daily
after completing at least 6 months of
treatment
OR
Active cancer
OR
Active cancer
daily
OR
Pregnant women
» enoxaparin: body weight <50 kg: 40 mg
50-69 kg: 60 mg subcutaneously twice daily;
body weight 70-89 kg: 80 mg subcutaneously
twice daily; body weight ≥90 kg: 100 mg
MANAGEMENT
subcutaneously twice daily

OR
Pregnant women
Ongoing
» dalteparin: body weight <50 kg: 5000 units
50-69 kg: 6000 units subcutaneously twice
daily; body weight 70-89 kg: 8000 units
subcutaneously twice daily; body weight ≥90
kg: 10,000 units subcutaneously twice daily
Secondary options
OR
daily
OR
OR
Active cancer
12 hours
OR
Active cancer
MANAGEMENT

Tertiary options
75
Ongoing
» aspirin: 75-150 mg orally once daily
» The extended phase covers the period from

3 months following DVT to indefinite.[26]
Bear in mind that not all patients will need
continued anticoagulation beyond 3 months.
The aim of the extended phase is secondary
prevention of new venous thromboembolism.
See the Prevention section for other
methods of secondary prevention aside from
anticoagulation.
Duration
Discuss with a senior colleague whether to
continue anticoagulation beyond 3 months
if the patient has a first presentation of
proximal DVT. This decision should assess
the individual patient’s risk of recurrence
of DVT versus bleeding risk, as well as
considering whether the DVT was provoked or
unprovoked.[12] Discuss the risks and benefits
of long-term anticoagulation with the patient, and
take their preferences into account.[12]
• A provoked DVT is a DVT associated

with a major transient risk factor that
was present in the 3 months prior to the
DVT.[12]
• An unprovoked DVT is a DVT in a
patient who had no pre-existing, major,
transient, provoking risk factor in the prior
3 months.[12]
• Major provoking risk factors include: major
surgery; trauma; significant immobility
(bedbound, unable to walk unaided, or
likely to spend a substantial proportion of
the day in bed or in a chair); pregnancy
or puerperium; use of oral contraceptive/
hormone replacement therapy.[12]
In general, anticoagulation can usually be

stopped after 3 months (or 3-6 months
for people with active cancer) if the DVT
was provoked, as long as the major transient
risk factor is no longer present and the clinical
course has been uncomplicated.[12]
• In the UK, some centres may continue

anticoagulation beyond 3 months for
patients with a minor transient risk factor
MANAGEMENT
(e.g., minor surgery).
Anticoagulation is usually continued for

longer than 3 months if the DVT was
unprovoked.[12]
Ongoing
• In practice, patients with persisting risk
factors (e.g., active cancer, autoimmune
conditions such as systemic lupus
erythematosus and inflammatory bowel
disease) usually continue anticoagulation
long-term, unless they had a major
provoking risk factor (e.g., major surgery).
• If the patient has active cancer,
anticoagulation is continued for at least 6
months.[12] In practice, this will be for at
least the duration of cancer treatment, or
until remission is achieved.
Annually reassess the risks/benefits of

continuing anticoagulation, as well as the
patient's general health and treatment
preferences, in all patients receiving extended
treatment beyond 3 months.[12] [60]
In general, offer continued treatment with the
anticoagulant used in the acute phase if it is well
tolerated.[12]
• If the patient has been started on a direct

oral anticoagulant other than apixaban
and this is not well tolerated, or the
clinical situation or patient preference
has changed, the National Institute for
Health and Care Excellence in the UK
recommends to consider switching to
apixaban if the patient does not have renal
impairment, active cancer, established
triple-positive antiphospholipid syndrome,
or extreme body weight (<50 kg or
>120 kg).[12] However, in practice,
many patients may prefer an alternative
anticoagulant that can be taken as a once-
daily regimen.
• In patients taking apixaban who need
ongoing anticoagulation for >6 months,
consider a dose reduction.[122] In
UK practice, if the patient is taking
rivaroxaban in this scenario, a dose
reduction may be considered if there is
concern about the risk of bleeding.
• In pregnant patients, continue low
molecular weight heparin for the
MANAGEMENT
remainder of the pregnancy and for at

least 6 weeks postnatally and until at least
3 months of treatment has been given in
total.[123]
77
Ongoing
• Note that warfarin is rarely used in UK
practice for a patient with active cancer.
Consider aspirin if the patient declines

or is unable to tolerate any form of oral
anticoagulant.[12]
recurrent venous thromboembolism
1st increase dose of anticoagulant OR switch

to alternative anticoagulant
» Seek advice from haematology for any patient

who has a recurrent venous thromboembolism
(VTE) despite adequate anticoagulation
treatment. Recurrent VTE is unusual
among patients receiving therapeutic-dose
anticoagulant therapy, except in those with active
cancer (7% to 9% on-therapy recurrence with
low molecular weight heparin).[13] [137] [138]
• Check adherence to anticoagulation

treatment.[12]
• Address other sources of
hypercoagulability (e.g., underlying
malignancy).[12]
• Consider other reasons for reduced
efficacy of anticoagulation (e.g.,
rivaroxaban not being taken with
food).[139]
» In the absence of any of the above issues,

options include:[12]

• Changing to a different anticoagulant with
a different mode of action.
» Note that these recommendations are

based on the National Institute for Health and
Care Excellence guideline in the UK, which
covers patients with proximal DVT only. In
UK practice, some experts may apply these
recommendations equally to patients with distal
(calf) DVT in the absence of recommendations
from guidelines. Seek advice from a specialist if
needed.
consider IVC filter
MANAGEMENT

» Patients with recurrent venous
thromboembolism despite treatment with
adequate anticoagulation can be considered for
a venous filter.[12]
Ongoing
» Note that these recommendations are
based on the National Institute for Health and
Care Excellence guideline in the UK, which
covers patients with proximal DVT only. In
UK practice, some experts may apply these
recommendations equally to patients with distal
(calf) DVT in the absence of recommendations
from guidelines. Seek advice from a specialist if
needed.
Primary prevention
Risk stratification
Assess the risk of venous thromboembolism (VTE) and bleeding for any patient admitted to hospital
(including those who are admitted as an inpatient or having a day procedure) using a suitable risk
assessment tool.[59]
• Patients who attend hospital but are not admitted (such as those in the emergency or outpatient
department) do not require risk assessment, unless they are discharged from hospital with temporary
lower-limb immobilisation (e.g., after trauma or orthopaedic surgery).[60]
Check your local protocols and consider the patient’s clinical circumstances when choosing a suitable
risk assessment tool. Use this risk assessment to weigh up the risks and benefits of pharmacological
prophylaxis.[59]
• For medical, surgical, and trauma patients:
• Carry out the risk assessment as soon as possible after admission, or by the time of the first
consultant review.[59] Reassess the patient at the consultant review or if their clinical situation
changes[59]
• The National Institute for Health and Care Excellence (NICE) in the UK recommends using the
Department of Health VTE risk assessment tool.[59] [Department of Health: risk assessment
for VTE] Other assessment tools include the Caprini RAM, the Geneva Risk Score, IMPROVE-
RAM, IMPROVEDD (which includes D-dimer), the Kucher Model, and the Padua Prediction
Score.[61] [62]
• For patients who are admitted to hospital or a midwife-led unit who are pregnant or have, within the
past 6 weeks, given birth, had a miscarriage, or had a termination of pregnancy:[59]
• Carry out the risk assessment on admission[59]

• NICE in the UK recommends using the Royal College of Obstetricians and Gynaecologists risk
assessment tool[59] [RCOG: VTE risk assessment tool]
• Reassess the patient:
• Within 6 hours of giving birth, having a miscarriage, or having a termination of pregnancy

• If their clinical condition changes and they:[59]
MANAGEMENT
• Are pregnant
OR
79
• Gave birth, had a miscarriage, or had a termination of pregnancy, within the past 6
weeks.
VTE prophylaxis in hospital

Pharmacological prophylaxis
Use your risk assessment to evaluate the patient’s risk of VTE against their risk of bleeding when deciding
whether to give pharmacological thromboprophylaxis.[59]
In general, if pharmacological prophylaxis is indicated in medical, surgical, or trauma patients, start this as
soon as possible and definitely within 14 hours of admission, unless there are special considerations for
timing (e.g., use of regional anaesthesia, specific types of surgery).[59] [60]
• Take into account your local protocols, any comorbidities (e.g., renal impairment, cancer), and
whether the patient is having surgery (and, if so, the type of surgery) when choosing type and dose of
pharmacological prophylaxis.[59]
• Options include low-dose low molecular weight heparin, fondaparinux, and unfractionated heparin.[59]
Apixaban, rivaroxaban, dabigatran, and aspirin are also appropriate for pharmacological prophylaxis
in patients undergoing joint replacement procedures, along with low molecular weight heparin and
fondaparinux.[59] [63] [64] [65] [66] [67] [68] [69] [70] [71] [72] [73] [74] Emerging evidence suggests
that apixaban may prevent VTE in intermediate- to high-risk ambulatory patients with cancer; risk of
major bleeding with apixaban was, however, greater than with placebo.[75]
Seek specialist advice if a patient is at high risk of VTE during pregnancy or the postnatal period; there
is uncertainty in current evidence about the risks and benefits of pharmacological prophylaxis for these
patients.[76]
Mechanical prophylaxis
Consider mechanical prophylaxis (intermittent pneumatic compression or anti-embolism stockings) for

patients in hospital who are at increased risk of VTE.[59] Mechanical prophylaxis is particularly useful for
patients with a high risk for bleeding or a contraindication to pharmacological prophylaxis.
• However, be aware that there is debate in the literature on the use of anti-embolism stockings for
prevention of VTE, particularly for patients who have undergone surgery who are already receiving
pharmacological prophylaxis.[77]
• NICE in the UK does not recommend mechanical prophylaxis for certain patient groups, such as
medical or obstetric patients.[59]
Choice of anti-embolism stockings versus intermittent pneumatic compression depends on the patient’s
acute condition and interventions (e.g., type of surgery), as well as any contraindications.[59] Consult your
local protocols, and seek expert advice if you are unsure.
Do not use anti-embolism stockings if the patient has:[59]
• An acute stroke (intermittent pneumatic compression is preferred)

• Suspected or known peripheral arterial disease
MANAGEMENT
• Peripheral arterial bypass grafting

• Peripheral neuropathy or other causes of sensory impairment
• A localised condition in which anti-embolism stockings may cause damage (e.g., fragile 'tissue paper'
skin, dermatitis, gangrene or recent skin graft)
• Known allergy to the material of manufacture (this also applies to intermittent pneumatic compression)
• Severe leg oedema
• Major limb deformity or unusual leg size or shape that prevents correct stocking fit.
If you are considering anti-embolism stockings and the patient has:[59]
• Venous ulcers or wounds: use clinical judgment and caution

• Suspected arterial disease: seek expert advice.
Monitor the patient carefully if they are using anti-embolism stockings.
• Remove the anti-embolism stockings to inspect the patient's skin condition at least daily.[59] If the
patient has a significant reduction in mobility, poor skin integrity, or any sensory loss, inspect their skin
condition 2 to 3 times a day, particularly over their heels and bony prominences.[59]
• Remove the anti-embolism stockings if the patient has marking, blistering, or discoloration
of their skin (particularly over their heels and bony prominences) or if they have any pain or
discomfort.[59] Consider using intermittent pneumatic compression as an alternative.[59]
Mobilisation and hydration
Encourage patients to mobilise as soon as possible and to ensure they are adequately hydrated.[59]
Extended-duration pharmacological prophylaxis

Consider continued prophylaxis after hospital discharge in certain patient groups, particularly those with
lower-limb immobilisation or following major orthopaedic surgery.[59]
More info: Extended-duration pharmacological prophylaxis
Five randomised trials enrolling over 40,000 patients have examined extended-duration prophylaxis
following hospitalisation for medical illness.[19] [20] [21] [22] [78] Regimens included low molecular
weight heparin or oral factor Xa inhibitors at a prophylactic dose for 4 to 6 weeks following discharge.
Inclusion criteria varied, but the most common reason for hospitalisation across studies was heart
failure. A pooled analysis revealed that extended prophylaxis reduced symptomatic VTE or VTE-related
death compared with standard of care (0.8% versus 1.2%; risk ratio [RR] 0.61, 95% CI 0.44 to 0.83; P
= 0.002) but increased the risk of major or fatal bleeding (0.6% versus 0.3%; RR 2.04, 95% CI 1.42 to
2.91; P <0.001).[79] Due to the very narrow margin of risks and benefits, further research is needed to
appropriately select medical patients for extended prophylaxis following hospital discharge.
Long-distance travel
Do not routinely use pharmacological prophylaxis for patients travelling long distances; instead, consider this
on a case-by-case basis (e.g., if the patient has a personal history of VTE).[80] Some evidence suggests
that elastic compression stockings may reduce the risk of VTE in these patients.[57] Do not use elastic
compression stockings for patients without risk factors; other measures, such as remaining mobile during
travel, are preferred.[80]
Secondary prevention
MANAGEMENT
For secondary prevention, if indicated, use extended-duration (beyond 3 months) anticoagulation.[12] Bear in
mind that not all patients will need continued anticoagulation beyond 3 months.
81
Duration of anticoagulation
Discuss with a senior colleague whether to continue anticoagulation beyond 3 months if the patient has a first
presentation of a proximal DVT. This decision should assess the individual patient’s risk of recurrence of DVT
versus bleeding risk, as well as considering whether the DVT was provoked or unprovoked. Discuss the risks
and benefits of long-term anticoagulation with the patient, and take their preferences into account.[12] In UK
practice, anticoagulation is rarely continued beyond 3 months if the patient has a distal (calf) DVT, unless
they have active cancer.
• Major provoking risk factors include: major surgery; trauma; significant immobility (bedbound, unable
to walk unaided, or likely to spend a substantial proportion of the day in bed or in a chair); pregnancy
or puerperium; use of oral contraceptive/hormone replacement therapy).[12]
In general, anticoagulation can usually be stopped after 3 months (or 3-6 months for people with active
cancer) if the proximal DVT was provoked, as long as the major transient risk factor is no longer present and
the clinical course has been uncomplicated.[12]
• In the UK, some centres may continue anticoagulation beyond 3 months for patients with a minor
transient risk factor (e.g., minor surgery).
Anticoagulation is usually continued for longer than 3 months if the proximal DVT was unprovoked and
proximal.[12]
• In practice, patients with persisting risk factors (e.g., active cancer, autoimmune conditions such as
systemic lupus erythematosus and inflammatory bowel disease) usually continue anticoagulation
long-term, unless they had a major provoking risk factor (e.g., major surgery). If the patient has active
cancer, anticoagulation is continued for at least 6 months.[12] In practice, this will be for at least the
duration of cancer treatment, or until remission is achieved.
Annually reassess the risks/benefits of continuing anticoagulation, as well as the patient's general health and
treatment preferences, in all patients receiving extended treatment beyond 3 months.[12] [60]
Note that anticoagulants offer secondary prevention benefits only as long as they are continued. There is
no legacy effect of a longer time-limited course of treatment; the risk of recurrent venous thromboembolism
(VTE) re-emerges as soon as the anticoagulant is discontinued.[162]
In general, offer continued treatment with the anticoagulant used in the acute phase if it is well tolerated.[12]
• If the patient has been started on a direct oral anticoagulant (DOAC) other than apixaban and this is
not well tolerated, or the clinical situation or patient preference has changed, the National Institute for
Health and Care Excellence in the UK recommends to consider switching to apixaban if the patient
does not have renal impairment, active cancer, established triple-positive antiphospholipid syndrome,
or extreme body weight (<50 kg or >120 kg).[12] However, in practice, many patients may prefer an
alternative anticoagulant that can be taken as a once-daily regimen.
• In patients taking apixaban who need ongoing anticoagulation for >6 months, consider a dose
reduction.[122] In UK practice, if the patient is taking rivaroxaban in this scenario, a dose reduction
may be considered if there is concern about the risk of bleeding.
MANAGEMENT
• In pregnant patients, continue low molecular weight heparin for the remainder of the pregnancy and for
at least 6 weeks postnatally and until at least 3 months of treatment has been given in total.[123]
Consider aspirin if the patient declines or is unable to tolerate any form of oral anticoagulant.[12]
More info: Risk of recurrent VTE
Many studies have attempted to identify subgroups of patients with unprovoked VTE who do not need to
be treated indefinitely with oral anticoagulation. There is strong evidence that the risk of recurrent VTE is
higher in the following patients: male sex; those with a diagnosis of a proximal DVT (versus isolated distal
[calf] DVT); those with ultrasound evidence of residual clot; those who have an elevated D-dimer 1 month
after stopping a 3- to 6-month course of oral anticoagulation; and those who had an unprovoked DVT.[27]
[124] [125] [126] [127] Several risk assessment models have been developed for this purpose, including
the DASH score, the Vienna Prediction Model, and the 'Men Continue and HER-DOO2' model.[128] The
latter model identifies a subset of women with low risk for recurrent VTE after an initial unprovoked event,
and a prospective validation study of this model was published.[129] However, these models are not
widely used in practice.
Other considerations
If anticoagulation is not continued beyond 3 months, or is interrupted, secondary prevention should also
involve episodic VTE prophylaxis when the risk of VTE is elevated.[59] For example, during:[12]
• Admission to hospital
• Surgery
• Pregnancy and the postnatal period
• Lower-limb immobilisation (e.g., plaster cast).
Other approaches that can also reduce the risk of VTE include:
• Maintaining a healthy weight

• Taking regular exercise
• Avoiding combined hormonal contraception and oral oestrogens
• Not smoking
• Using a statin (when indicated for hyperlipidaemia).
Patient discussions
If warfarin is chosen for anticoagulation, initiate careful discussion with the patient about its proper use
and the need for regular follow-up and monitoring of international normalised ratio (INR). As a guide,
cover the following points to ensure safe and effective management.
• Warfarin makes the blood more difficult to clot and therefore carries a risk of bleeding.
• The effect of the drug is measured with a blood-clotting test called the INR.
• Warfarin dose frequently changes over time; commonly, dosing varies according to the day of the
week.
• Patients should be given advice on daily dosing, given the day-to-day fluctuations in dose.
• The target INR values are generally between 2 and 3.
• Many drugs interact with warfarin, so the clinician who oversees the warfarin treatment must be
notified whenever a new medicine (e.g., prescription or over-the-counter medicine, supplement, or
MANAGEMENT
herbal therapy) is started for the first time, or when a current medication is stopped or the dose is
adjusted. Non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided or used with extreme
caution under clinical supervision.
• Even when medications do not interact with INR testing, they may still increase the risk of bleeding
through pharmacodynamic interactions (NSAIDs, selective serotonin-reuptake inhibitors).
83
• Dietary changes can affect the INR, especially the intake of foods with high amounts of vitamin K
(e.g., spinach, broccoli); eating any amount of vegetables or food high in vitamin K is acceptable,
so long as the intake is consistent from week to week. Alcohol should be consumed with caution
and only in small amounts. Grapefruit juice should be avoided.
• Activities that carry a high risk of trauma or serious bleeding should be avoided, or if this is not
possible, additional safety precautions should be taken.
• The INR must be checked (monitored) frequently, with blood tests, often once or twice weekly until
the stable dose is reached, then on an extended interval (4-12 weeks) thereafter.
• Advise the patient on how to handle a missed dose (the approach may vary according to the
anticoagulation clinic).
• Make sure the patient is very clear about the daily dose of warfarin and the colours of their different
warfarin tablets (a pill organiser may help).
Although direct oral anticoagulants (DOACs) do not require coagulation assay laboratory monitoring and
drug-drug interactions are minimised when compared with warfarin, there are still some medications that
interact with DOACs and can lead to either increased risk of bleeding or increased risk of thrombosis
(e.g., primidone, amiodarone, diltiazem, verapamil, rifampicin, phenytoin, phenobarbital). Interactions are
most commonly mediated via cytochrome P450 enzyme (CYP450) and/or the transporter permeability
glycoprotein (P-gp).[161]
Give the patient information about the range of signs and symptoms of bleeding and recurrent
thrombosis, and advise them to seek immediate medical attention if these occur.
MANAGEMENT
Deep vein thrombosis Follow up
Monitoring
Monitoring
FOLLOW UP
For patients treated with intravenous heparin, activated partial thromboplastin time (aPTT) or calibrated
anti-Xa activity is measured:
• Prior to heparin initiation, to obtain a baseline

• 6 hours after initiation of the infusion
• 6 hours after each adjustment in the dose
• At least once daily thereafter when the therapeutic level is achieved (defined as 2 measurements in
the target range without interval dose adjustment).
Target values for aPTT are based on the local laboratory's standardised aPTT values, which should
correspond to a heparin level between 0.4 U/mL and 0.8 U/mL. Calibrated anti-Xa activity is an alternative
to aPTT. Platelet count should be measured at baseline, then on days 3 and 5, to observe for the
development of heparin-induced thrombocytopenia. Full blood count should be obtained to evaluate early
signs of bleeding through decreases in haematocrit/haemoglobin.
For patients treated with low molecular weight heparin (LMWH) or fondaparinux, no therapeutic
monitoring of anticoagulation is needed in most patients. Changes in patient weight may require
adjustment of the dose. Renal function indices, such as serum creatinine and urea, should be obtained to
determine initial and ongoing appropriateness of LMWH and fondaparinux as both require discontinuation
or dose adjustment in renal impairment.
Frequent international normalised ratio (INR) monitoring of patients who are treated with warfarin is
required. This is preferably done by experts or specialised anticoagulation clinics, whenever possible.
Anticoagulant therapy, although potentially life-saving, has inherent bleeding risks. A systematic approach
will reduce the likelihood of adverse events.[158] In the UK, patients can self-monitor their INR using
portable point-of-care instruments; this is used by the anticoagulation clinic to inform dosing.[159]
The initial dose and titration of warfarin is more efficient and leads to better patient outcomes if an
estimating equation is used, rather than a fixed-dose initiation algorithm.[113] [114]
Rivaroxaban, apixaban, edoxaban, and dabigatran do not require laboratory monitoring for anticoagulant
effect. It is recommended that attention be directed to any changes in renal or liver function testing as
clinically indicated (e.g., at baseline then as indicated). With direct oral anticoagulants (DOACs), any
changes in concomitant interacting medications (addition or discontinuation) should also be closely
monitored because this may require dose adjustment or discontinuation of the current DOAC, or a change
to an alternative anticoagulant.
Patients should be assessed for the development of post-thrombotic syndrome; this is under-recognised
in practice. In addition, patients who have pulmonary embolism should be evaluated clinically over time
to determine whether they have chronic thromboembolic pulmonary hypertension due to unresolved
pulmonary emboli, which may occur in up to 4% of patients.[160]
85
Complications
Complications Timeframe Likelihood

FOLLOW UP
pulmonary embolism (PE) short term high
The frequency, size, and symptoms of PE are variable. Among patients with proven thrombosis, lung
scans at the start of antithrombotic treatment showed a high probability of PE in 51% of patients.[147]
PE is treated in the same fashion as DVT, unless there are signs of haemodynamic instability (e.g.,
cardiac arrest, obstructive shock, persistent hypotension); these patients should be treated with primary
reperfusion. Selected patients with PE are candidates for inferior vena cava filter.
bleeding during initial treatment short term medium
Most episodes of bleeding during anticoagulation result from a previously unknown pathological
lesion, such as duodenal ulcer, angiodysplasia in the colon, microvascular disease (such as a striatal
intracerebral bleed in a patient with hypertension), or rare conditions, such as amyloid angiopathy in the
central nervous system.[150]
If the patient is taking warfarin and experiences major bleeding, inactivated 4-factor prothrombin complex
concentrate (PCC) should be given promptly if clinically indicated. Oral or intravenous phytomenadione
(vitamin K) can also be given either alone or in conjunction with PCC, but the effect of vitamin K on
warfarin is delayed and typically sustained for days. Intravenous administration is preferred in the setting
of intracranial haemorrhage.[151] The effect of the PCC can be assessed immediately by measuring the
international normalised ratio.[152] Fresh frozen plasma (FFP) has also been described as a means of
reversing the effect of warfarin, but carries greater risk, is much slower to administer, and confers a much
larger volume load than PCC. Guidelines favour PCC over FFP.[153]
Specific reversal agents are available for direct oral anticoagulants. Dabigatran can be reversed with
idarucizumab.[111] Recombinant coagulation factor Xa (andexanet alfa) has been approved in the UK
for patients with major or life-threatening bleeding on rivaroxaban and apixaban, although it is only
approved for gastrointestinal bleeding in England. Of note, andexanet alfa is not approved for the reversal
of edoxaban in the UK, likely due to low study enrollment of these patients.[154]
Protamine should be used to reverse unfractionated heparin and may be used to reverse low molecular
weight heparin, although it is not as effective.[155]
Non-specific reversal strategies have been tested for newer anticoagulants as well, but the level of
evidence for these is low. PCC has also been shown to normalise coagulation studies in normal volunteers
given high-dose rivaroxaban or apixaban. It is not known if this is the case with edoxaban. Dabigatran
does not appear to be reversed by PCC, though factor VIII inhibitor bypassing fraction (also known as
factor eight inhibitor bypass activity) may affect dabigatran, and about 60% of dabigatran can be removed
by dialysis. Activated charcoal may inhibit absorption of recently taken oral anticoagulants.
Inferior vena cava filter may be indicated in selected patients with acute bleeding during anticoagulation.
heparin-induced thrombocytopenia (HIT) short term low
Antibodies may develop to heparin-platelet factor IV complexes starting 5 to 7 days after initial exposure
to heparin or as early as <1 day in patients with recent (<30 days prior) heparin exposure.[146] The
antibodies aggregate platelets, lead to thrombocytopenia, and might result in acute arterial and venous
thrombosis as well as bleeding.

If there is a history of recent heparin exposure, development of HIT can be immediate. It develops in
between 1% to 2% of patients treated with therapeutic doses of heparin; however, it is rare when heparin
FOLLOW UP
is given subcutaneously to patients as a form of prophylaxis, but is possible and should be evaluated in
patients receiving prophylactic heparin with an elevated Warkentin Probability Scale ('4T score').
The incidence of HIT is lower in patients treated with low molecular weight heparin (LMWH). Although
there have been several reported cases of fondaparinux-associated HIT, it is a rare occurrence.
Due to the risk of HIT, platelet count should be measured at baseline, then on days 3 and 5, to observe for
the development of HIT.
Suspected or confirmed HIT should be managed by promptly discontinuing heparin or LMWH, and
substituting a direct thrombin inhibitor such as argatroban or danaparoid.[26] Bivalirudin, desirudin, and
fondaparinux have also been suggested as suitable options, but are not licensed for active HIT in the
UK.[26] [IHI: anticoagulant toolkit – reducing adverse drug events] Anticoagulation may be transitioned to
warfarin, if a parenteral anticoagulant is initially chosen, when the platelet count returns to baseline.
The Warkentin Probability Scale ('4T score') for HIT can be used to estimate the pretest probability of
HIT.[99]
heparin resistance/aPTT confounding short term low
Patients might require very large doses of intravenous heparin and never achieve a therapeutic activated
partial thromboplastin time (aPTT).[156] This might be caused by very high levels of clotting factors, such
as fibrinogen.
In patients who require extremely large daily doses of unfractionated heparin (i.e., >2500 units/hour)
without achieving a therapeutic aPTT, it is recommended that the calibrated anti-Xa activity be measured
and used to guide heparin dosing.
In certain patients, such as those with antiphospholipid syndrome, the aPTT value may create a result
in the target range with only very low doses of heparin (or even no heparin). Calibrated anti-Xa activity
should be used to manage heparin in such cases if heparin is the drug chosen.
post-thrombotic syndrome long term medium
Caused by chronic obstruction of venous outflow and/or destruction of venous valves, resulting in venous
hypertension from venous insufficiency and/or venous outflow obstruction.[148]
Up to half of patients develop some signs or symptoms of post-thrombotic syndrome and this usually
occurs within 2 years of the acute DVT episode.[149]
bleeding during long-term/extended treatment variable low
The incidence is greatest in the first 3 months of treatment when on warfarin. Most bleeds are minor.
Fatality is relatively rare, and the rate is greatest for intracranial bleeds. Age over 75 years is associated
with an increase in the incidence of intracranial bleeding. Patients with renal impairment have a higher rate
of major bleeding. In general, bleeding is less with direct oral anticoagulants (e.g., apixaban, edoxaban,
dabigatran) when compared with warfarin for the management of venous thromboembolism.
87

osteoporosis due to heparin treatment variable low
FOLLOW UP
While the risk of osteoporotic fracture is as high as 2% if unfractionated heparin is given throughout
pregnancy, there are only a handful of cases published where osteoporotic fracture occurred in those on
low molecular weight heparin.[157]
There is conflicting evidence as to whether this develops in patients during chronic warfarin therapy.
Prognosis
DVT rarely affects the overall prognosis of the patient; the presence or absence of an underlying malignancy,
and the presence or absence of underlying medical comorbidities, such as liver disease or chronic kidney
disease, remain the major prognostic determinants among patients with DVT. People with cancer have
reduced survival rates compared with people without cancer, and cancer patients who sustain DVT have a
shorter life expectancy than cancer patients without venous thromboembolism (VTE; although this appears
to be related to an association with more severe malignancy and VTE, rather than to the DVT itself). If a
patient dies due to DVT, this is usually caused by concomitant pulmonary embolus or major haemorrhage as
a complication of the anticoagulation therapy.
In one systematic review, during the initial 3 months of anticoagulation, the rate of recurrent fatal VTE was
0.4% with a case-fatality rate of 11.3%. The rate of fatal major bleeding events was 0.2% with a case-fatality
rate of 11.3%. After anticoagulation, the rate of fatal recurrent VTE was 0.3 per 100 patient-years with a
case-fatality rate of 3.6%.[140]
In community cohort studies, the incidence of acute recurrent DVT within 60 days is as high as 25% to 30%.
The reasons for this acute recurrence are not known, but subtherapeutic anticoagulant therapy or patient
non-adherence to therapy may contribute.[141] [142]
In patients with acute DVT or pulmonary embolism enrolled in prospective cohort studies, only 5% of patients
develop recurrent VTE during the initial 6 months of anticoagulation; however, 30% of patients develop
recurrent VTE between 6 months and 5 years after the initial event, if off anticoagulation.[143] [144]
Compared with patients with no thrombophilic defects, the rate of recurrence during warfarin therapy is not
increased in the presence of one or more defects.[145]
The incidence of major life-threatening haemorrhage owing to anticoagulant treatment is low, with the precise
risk varying by anticoagulant agent and patient characteristics.
Recurrence
A significant factor that determines the risk of recurrence is whether a DVT is provoked or unprovoked.
• Major provoking risk factors include: major surgery; trauma; significant immobility (bedbound, unable
to walk unaided, or likely to spend a substantial proportion of the day in bed or in a chair); pregnancy
or puerperium; use of oral contraceptive/hormone replacement therapy).[12]
The principal means of preventing recurrence (secondary prevention) is the extended duration (beyond 3
months) of anticoagulation. Bear in mind that not all patients will need continued anticoagulation beyond 3
months. However, other considerations may be required (e.g., VTE prophylaxis at periods of higher risk). See
Secondary prevention under Prevention for more information.
FOLLOW UP
Seek advice from haematology for any patient who has a recurrent VTE despite adequate anticoagulation
treatment. Recurrent VTE is unusual among patients receiving therapeutic-dose anticoagulant therapy,
except in those with active cancer (7% to 9% on-therapy recurrence with low molecular weight heparin).[13]
[137] [138]
• Check adherence to anticoagulation treatment.[12]

• Address other sources of hypercoagulability (e.g., underlying malignancy).[12]
• Consider other reasons for reduced efficacy of anticoagulation (e.g., rivaroxaban not being taken with
food).[139]
In the absence of any of the above issues, options include:[12]

• Changing to a different anticoagulant with a different mode of action.
89
Deep vein thrombosis Guidelines
Diagnostic guidelines
United Kingdom
Venous thromboembolic diseases: diagnosis, management and

thrombophilia testing
Published by: National Institute for Health and Care Excellence Last published: 2020
Venous thromboembolism in over 16s: reducing the risk of hospital-acquired

deep vein thrombosis or pulmonary embolism
Prevention and management of venous thromboembolism: a national clinical

guideline
Published by: Scottish Intercollegiate Guidelines Network Last published: 2014
GUIDELINES
Clinical guidelines for testing for heritable thrombophilia

Published by: British Society for Haematology Last published: 2010
Europe
European Society for Vascular Surgery (ESVS) 2021 clinical practice

guidelines on the management of venous thrombosis
Published by: European Society for Vascular Surgery Last published: 2021
2019 ESC guidelines for the diagnosis and management of acute pulmonary
embolism developed in collaboration with the European Respiratory Society
(ERS)
Published by: European Society of Cardiology Last published: 2019
North America
NCCN clinical practice guidelines in oncology: cancer-associated venous

thromboembolic disease
Published by: National Comprehensive Cancer Network Last published: 2021
ACR-AIUM-SPR-SRU practice parameter for the performance of peripheral

venous ultrasound examination
Published by: American College of Radiology; American Institute Last published: 2019
of Ultrasound in Medicine; Society of Pediatric Radiology; Society of
Radiologists in Ultrasound
American Society of Hematology 2018 guidelines for management of venous

thromboembolism: diagnosis of venous thromboembolism
Published by: American Society of Hematology Last published: 2018
GUIDELINES
thromboembolism: venous thromboembolism in the context of pregnancy
ACR appropriateness criteria: suspected lower extremity deep vein

thrombosis
Published by: American College of Radiology Last published: 2018
Management of venous thromboembolism

Published by: Anticoagulation Forum Last published: 2016
Diagnosis and management of iliofemoral deep vein thrombosis: clinical

practice guideline
Published by: Interdisciplinary Expert Panel on Iliofemoral Deep Vein Last published: 2015
Thrombosis
Diagnosis of DVT: antithrombotic therapy and prevention of thrombosis, 9th

edition
Published by: American College of Chest Physicians Last published: 2012
Asia
Diagnosis and treatment of lower extremity deep vein thrombosis: Korean

practice guidelines
Published by: Korean Society of Interventional Radiology; Korean Last published: 2016
Society for Vascular Surgery
91
Treatment guidelines
United Kingdom
Postnatal care
Venous thromboembolic diseases: diagnosis, management and

thrombophilia testing
Venous thromboembolism in over 16s: reducing the risk of hospital-acquired

deep vein thrombosis or pulmonary embolism
GUIDELINES
Thromboembolic disease in pregnancy and the puerperium: acute

management
Published by: Royal College of Obstetricians and Gynaecologists Last published: 2015
Reducing the risk of venous thromboembolism during pregnancy and the

puerperium
Published by: Royal College of Obstetricians and Gynaecologists Last published: 2015
Prevention and management of venous thromboembolism: a national clinical

guideline
Published by: Scottish Intercollegiate Guidelines Network Last published: 2014
Guidelines on travel-related venous thrombosis

Guidelines on use of vena cava filters

North America
NCCN clinical practice guidelines in oncology: cancer-associated venous

thromboembolic disease
Published by: National Comprehensive Cancer Network Last published: 2021
Antithrombotic therapy for VTE disease: second update of the CHEST

guideline and expert panel report

thromboembolism: prevention and treatment in patients with cancer
Venous thromboembolism prophylaxis and treatment in patients with

cancer
GUIDELINES
Published by: American Society of Clinical Oncology Last published: 2020

thromboembolism: treatment of deep vein thrombosis and pulmonary
embolism

thromboembolism: optimal management of anticoagulation therapy

thromboembolism: venous thromboembolism in the context of pregnancy
Management of venous thromboembolism

Published by: Anticoagulation Forum Last published: 2016
Diagnosis and management of iliofemoral deep vein thrombosis: clinical

practice guideline
Published by: Interdisciplinary Expert Panel on Iliofemoral Deep Vein Last published: 2015
Thrombosis
Prevention of VTE in nonorthopedic surgical patients: antithrombotic therapy

and prevention of thrombosis, 9th edition
Prevention of VTE in nonsurgical patients: antithrombotic therapy and

prevention of thrombosis, 9th edition
93
North America
Preventing venous thromboembolic disease in patients undergoing elective

hip and knee arthroplasty
Published by: American Academy of Orthopaedic Surgeons Last published: 2011
Management of massive and submassive pulmonary embolism, iliofemoral

deep vein thrombosis, and chronic thromboembolic pulmonary hypertension
Published by: American Heart Association Last published: 2011
GUIDELINES
Deep vein thrombosis Online resources
Online resources
1. Department of Health: risk assessment for VTE (external link)
2. RCOG: VTE risk assessment tool (external link)
3. Algorithm for the diagnosis of deep vein thrombosis (external link)
4. IHI: anticoagulant toolkit – reducing adverse drug events (external link)
5. Warfarin dosing (external link)
ONLINE RESOURCES
95
Deep vein thrombosis References
Key articles
• National Institute for Health and Care Excellence. Venous thromboembolic diseases: diagnosis,
REFERENCES
management and thrombophilia testing. March 2020 [internet publication]. Full text
• Kakkos SK, Gohel M, Baekgaard N, et al. Editor's choice: European Society for Vascular Surgery
(ESVS) 2021 clinical practice guidelines on the management of venous thrombosis. Eur J Vasc
Endovasc Surg. 2021 Jan;61(1):9-82. Full text Abstract
• Mazzolai L, Aboyans V, Ageno W, et al. Diagnosis and management of acute deep vein thrombosis:
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peripheral circulation and pulmonary circulation and right ventricular function. Eur Heart J. 2018 Dec
14;39(47):4208-18. Full text Abstract
• National Institute for Health and Care Excellence. Venous thromboembolism in over 16s: reducing
the risk of hospital-acquired deep vein thrombosis or pulmonary embolism. August 2019 [internet
publication]. Full text
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Deep vein thrombosis Images
Images
IMAGES
Figure 1: Phlegmasia cerulea dolens: swelling of the left leg and bluish discoloration of the foot
Cooper RM, et al. Phlegmasia cerulea dolens, a rare complication of deep vein thrombosis. Emerg Med J.
2008 Jun;25(6):334
109
IMAGES Deep vein thrombosis Images
Figure 2: Short-axis ultrasound view showing the femoral vein (FV) and profunda femoris vein (PFV) adjacent
to the femoral artery before compression (left) and compressed (right)
From the collection of Jeffrey W. Olin; used with permission
Deep vein thrombosis Disclaimer
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Contributors:
// Acknowledgements:
BMJ Best Practice would like to gratefully acknowledge the previous expert contributors, whose work
has been retained in parts of the content:Scott M. Stevens, MDDirectorThrombosis ClinicIntermountain
Medical CenterMurrayProfessor of MedicineDepartment of MedicineIntermountain Healthcare and
University of UtahSalt Lake CityUTScott C. Woller, MDDirectorThrombosis ClinicIntermountain Medical
CenterMurrayProfessor of MedicineDepartment of MedicineIntermountain Healthcare and University of
UtahSalt Lake CityUTGabriel V. Fontaine, PharmD, MBA, BCPSClinical Pharmacy ManagerCritical Care
and Emergency MedicineAdvanced Clinical PharmacistNeuroscience Critical CareIntermountain Medical
CenterMurrayUTDisclosures: SMS declares that he has no competing interests. SCW serves as co-chair
of the American College of Chest Physicians (CHEST) guideline on the treatment of venous thrombotic
disease. GVF has received consulting fees and honoraria from Alexion Pharmaceuticals.
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Lara Roberts, MBBS, MD(Res), MRCP, FRCPath

Consultant Haematologist
King's College Hospital, London, UK
DISCLOSURES: LR declares that she has no competing interests.
Steve Goodacre, MBChB, MRCP, DipIMC, FRCEM, MSc, PhD

Professor of Emergency Medicine
University of Sheffield, Consultant in Emergency Medicine, Sheffield Teaching Hospitals NHS Foundation
Trust, Sheffield, UK
DISCLOSURES: SG was Chief Investigator or joint Chief Investigator for the NIHR-funded DiPEP, TiLLI,
and VTEAM studies. He has also undertaken consultancy work on behalf of the University of Sheffield for
ThinkSono.
// Expert Advisers:
Ian Chet ter, MBChb, FRCS (eng), MD, FRCS (Gen surg), PGCert Medical Ultrasound, PGDip
Clinical Education
Chair of Surgery
University of Hull, Honorary Consultant Vascular Surgeon, Hull University Teaching Hospitals NHS Trust,
Hull, UK
DISCLOSURES: IC declares he has no competing interests
// Editors:
Annabel Sidwell,
Section Editor and Comorbidities Editor, BMJ Best Practice
DISCLOSURES: AS declares that she has no competing interests.
Tanna z Aliabadi-Oglesby,
Lead Section Editor, BMJ Best Practice
Contributors:
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Adam Mitchell,
Drug Editor, BMJ Best Practice
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Deep Vein Thrombosis

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Deep Vein Thrombosis

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Deep vein thrombosis

Straight to the point of care

Last updated: Mar 10, 2022

present as pulmonary embolism (with or without concomitant symptoms of DVT).[2]

major surgery within the preceding 12 weeks

medical hospitalisation within the preceding 2 months

recent trauma or fracture

pregnancy and the postnatal period

paralysis, paresis, or recent plaster immobilisation of the lower extremities

prothrombin gene G20210A mutation

protein C or protein S deficiency

antiphospholipid antibody syndrome

In contrast to the hereditary thrombophilias, antiphospholipid syndrome likely predicts a higher

use of specific drugs

Erythropoietin is associated with an increased risk of DVT in patients with cancer.

been associated with a 2-fold increased VTE risk.[53]

recent long-distance air travel

There is a clear association between DVT and the following:

(a) Superficial versus deep

• Deep vein thrombosis

• Thrombi form within veins deep to the muscular tissue planes.

(b) Proximal versus distal

• Proximal venous thrombosis

• Distal or calf vein thrombosis

(c) Acute versus subacute, or chronic

DVT: upper extremity (not covered in this topic)

(a) Superficial versus deep thrombosis

(b) Proximal versus distal

(c) Acute versus subacute, or chronic

• Symptoms and signs of DVT are usually unilateral, and include:

• Calf swelling (or, more rarely, swelling of the entire leg)

• Significant risk factors include:

[Algorithm for the diagnosis of deep vein thrombosis]

• Calf swelling (or, more rarely, swelling of the entire leg)

• Localised pain along the deep venous system

Dilated superficial veins over the foot and leg

• This is also a symptom of PCD.

Ask about significant risk factors, which include:

Examine the patient for:

• Oedema and dilated collateral superficial veins on the affected side

• Large or ruptured popliteal cyst (Baker's cyst)

Assessment of pretest probability (Wells score)

Wells#score elements Score

Active cancer (any treatment within past 6 1

Calf swelling where affected calf circumference 1

Prominent superficial veins (non-varicose) 1

Pitting oedema (confined to symptomatic leg) 1

Swelling of entire leg 1

Localised pain along distribution of deep venous 1

Recent bed rest for >3 days or major 1

Previous history of DVT or pulmonary embolism 1

Alternative diagnosis at least as probable 1

Quantitative D-dimer level

If D-dimer testing is indicated, consider:[12]

DVT likely (Wells ≥2)

DVT unlikely (Wells <2)

• A venous ultrasound, with the result available within 4 hours

More info: D-dimer

More info: Ultrasound approaches

Colour flow ultrasound is sometimes performed in conjunction with B-mode image

DVT likely (Wells ≥2)

• If the result of a whole-leg ultrasound is negative:

• Check your local protocol because recommendations vary

• Some UK centres advocate a repeat ultrasound in this scenario