Venous Thrombosis in Pregnancy

Diagnosis and management

MODERATOR :DR SANJANA HALDER

SPEAKER:DR NEPHY T S DARRSHINI MBBS;DGO
PD-CET POST GRADUATE TRAINEE
DIAMOND HARBOUR GOVT.MEDICAL COLLEGE
HOSPITAL
Pregnancy is a hypercoagulable state because of an alteration
in the thrombotic and fibrinolytic systems.
There is an increase in clotting factors VIII, IX, X and fibrinogen
levels, and a reduction in protein S and antithrombin (AT) III
concentrations.
The net result of these changes is thought to be an
evolutionary response to reduce the likelihood of
haemorrhage following delivery )
(OBSTETRICS by Ten Teachers 20th..pdf
 • A Thrombosis is a blood clot in a blood vessel (a vein or an artery). Venous
thrombosis occurs in a vein. Veins are the blood vessels that take blood back to
the heart and lungs whereas arteries take the blood away.
• A deep vein thrombosis (DVT) is a blood clot that forms in a
deep vein of the leg, calf or pelvis

RCOG 2015
The deep venous system of the lower limb

Fig 1- The deep venous system of the lower limb. In pregnant women, the majority of DVTs form in the proximal veins, and the left leg is most commonly affected.
Venous thromboembolism (VTE) is a collective term
that describes
• Deep vein thrombosis (DVT)
1. Acute
2. Subacute
3. chronic
• Pulmonary embolism (PE).
RISK FACTORS
• Pre-existing
• Obstetric
• Transient/new onset
Risk factors for venous thromboembolism in pregnancy
and the puerperium
• PRE-EXISTING
Previous VTE
Thrombophilia-
- HERITABLE
• Antithrombin deficiency
• Protein C deficiency HIGH RISK
• Protein S deficiency

• Factor V Leiden-heterozygous
• Prothrombin gene mutation-G20210A mutation LOW RISK
- ACQUIRED
• Antiphospholipid antibodies
• Persistent lupus anticoagulant and/or persistent moderate/high titre anticardiolipin
antibodies and/or β2-glycoprotein 1 antibodies RCOG 2015
Medical comorbidities
e.g. cancer; heart failure; active SLE, inflammatory polyarthropathy or IBD; nephrotic
syndrome; type I diabetes mellitus with nephropathy; sickle cell disease; current
intravenous drug user
Age > 35 years
Obesity (BMI ≥ 30 kg/m2) either pre-pregnancy or in early pregnancy
Parity ≥ 3 (a woman becomes para 3 after her third delivery)
Smoking
Gross varicose veins (symptomatic or above knee or with associated
phlebitis, oedema/skin changes)
Paraplegia

RCOG 2015
• OBSTETRIC RISK FACTORS
Multiple pregnancy
Current pre-eclampsia
Caesarean section
Prolonged labour (> 24 hours)
Mid-cavity or rotational operative delivery
Stillbirth
Preterm birth
Postpartum haemorrhage (> 1 litre/requiring transfusion)
RCOG 2015
NEW ONSET/TRANSIENT
These risk factors are potentially reversible and may develop at later stages in gestation than the initial risk assessment
or may resolve and therefore what is important is an ongoing individual risk assessment

Any surgical procedure in pregnancy or puerperium except immediate repair of

the perineum, e.g. appendicectomy, postpartum sterilisation
Bone fracture
Hyperemesis, dehydration
Ovarian hyperstimulation syndrome (first trimester only) Assisted reproductive
technology (ART), in vitro fertilisation (IVF)
Admission or immobility (≥ 3 days’ bed rest) e.g. pelvic girdle pain restricting
mobility
Current systemic infection (requiring intravenous antibiotics or admission to
hospital) e.g. pneumonia, pyelonephritis, postpartum wound infection
Long-distance travel (> 4 hours)
RCOG 2015
RISK ASSESSMENT
• All patients should be assessed for VTE risk multiple times in
pregnancy ,including during:

1.Presentation for prenatal care

2.Hospitalization for antepartum indication
3.Delivery hospitalization(in house post partum)
4.Discharge from a delivery/ hospitalization
PREVENTING DVT
The RCOG green top guidelines have classified patients at risk for
thromboembolism into
• high risk and
• intermediate risk
• Low risk groups
RCOG 2015
RCOG 2015
RCOG 2015
 Risk assessment of VTE RCOG
Risk factor score
Previous VTE (except a single event related to major surgery) 4

Previous VTE provoked by major surgery 3

Known high-risk thrombophilia 3
Medical comorbidities e.g. cancer, heart failure; active systemic lupus erythematosus, inflammatory 3
polyarthropathy or inflammatory bowel disease; nephrotic syndrome; type I diabetes mellitus with nephropathy; sickle
cell disease; current intravenous drug user

Family history of unprovoked or estrogen-related VTE in first-degree relative 1

Known low-risk thrombophilia (no VTE) 1a

Age (> 35 years) 1
Obesity 1 or 2b 1 or 2b
Parity ≥ 3 1 1
Smoker 1
Gross varicose veins 1
 Risk assessment for VTE
RCOG
Pre exisisting risk factors (obstetric causes) score

Pre eclampsia in current pregnancy 1

ART/IVF(antenatal only) 1
Multiple pregnancy 1
Elective Caesarean section 1
Caesarean section in labour 2

Prolonged labour >24hours 1

PPH >1 L blood loss/requiring blood transfusion 1

Difficult operative vaginal devlivery/rotational/forceps 1

delivery
Preterm birth <37wks 1
Still birth 1
Risk assessment for VTE RCOG
New onset/transient factors score

3
Any surgical procedure in pregnancy or puerperium except immediate
repair of the perineum, e.g. appendicectomy, postpartum sterilisation
hyperemesis 3
OHSS(1st trimester especially in IVF) 4

Current systemic infection 1

Immobility >3 days or prolonged travel >4 hours/dehydration 1
RCOG 2015
 Timing of initiation of RCOG
thromboprophylaxis

4 or more risk factors 3 risk factors 2 risk factors

Through out pregnancy+ After 28 weeks of pregnancy+

6weeks post partum 6 weeks post partum Postpartum 10days
 METHODS OF PROPHYLAXIS
General measures Mechanical
1)Vigillance 1)mechanical calf Drugs
2)Avoid dehydration compression 1)Heparin
3)mobilisation 2)Gradual elastic 2)others
compression stockings

1)Moderate risk women

when LMWH is
All women contradicated
2)High risk women along
with LMWH
3)Prior VTE with in 2 years
AGENT TO BE USED FOR
THROMBOPROPHYLAXIS
1.LOW MOLECULAR WEIGHT HEPARIN
2.UNFRACTIONATED HEPARIN
3.DANAPAROID
4.FONDAPARINUX
5.WARFARIN
1.LOW MOLECULAR WEIGHT HEPARIN

• LMWHs are the agents of choice for antenatal and postnatal

thromboprophylaxis.
• Doses of LMWH are based on weight. For thromboprophylaxis the
booking or most recent weight can be used to guide dosing.
• It is only necessary to monitor the platelet count if the woman has
had prior exposure to unfractionated heparin (UFH).
• Monitoring of anti-Xa levels is not required when LMWH is used for
thromboprophylaxis.
• Doses of LMWH should be reduced in women with renal impairment.
• LMWH is safe in breastfeeding.
Contraindications to LMWH
• in women at risk of bleeding after careful consideration of the
balance of risks of bleeding and thrombosis.
• Women with previous or current allergic reactions to LMWH
RCOG 2015
2.UNFRACTIONATED HEPARIN

• In women at very high risk of thrombosis (see Appendix IV), UFH may
be used peripartum in preference to LMWH where there is an
increased risk of haemorrhage or where regional anaesthetic
techniques may be required.
• If UFH is used after caesarean section (or other surgery), the platelet
count should be monitored every 2–3 days from days 4–14 or until
heparin is stopped.
ACOG 2018
3.DANAPAROID
• Potential use of danaparoid should be in conjunction with a
consultant haematologist with expertise in haemostasis and
pregnancy.
• mostly used in patients intolerant of heparin, either because of HIT or
a skin allergy to heparins
4.FONDAPARINUX
• Fondaparinux should be reserved for women intolerant of heparin
compounds.
• Fondaparinux use in pregnancy should be in conjunction with a
consultant haematologist with expertise in haemostasis and
pregnancy.
• a synthetic pentasaccharide that acts through inhibition of factor Xa
via antithrombin. It is licensed in the UK for the prevention and
treatment of VTE outside pregnancy and has a broadly similar efficacy
to LMWH –not recommended in pregnancy
5.WARFARIN
• Warfarin use in pregnancy is restricted to the few situations where
heparin is considered unsuitable, e.g. some women with mechanical
heart valves.
• Women receiving long-term anticoagulation with warfarin can be
converted from LMWH to warfarin postpartum when the risk of
haemorrhage is reduced, usually 5–7 days after delivery.
• Warfarin is safe in breastfeeding.
 NEWER ANTICOAGULANTS

DANAPAROID PREFERRED IN HIT

LEPIRUDIN ANTENATAL –BETTER AVOIDED

POST NATAL ALTERNATIVE TO DANAPARANOID
FONDAPARINUX AVOIDED

RIVAROXABAN ,APIXABAN INADEQUATE DATA

DABIGATRAN,XIMELAGATRAN IN ADEQUATE DATA

DEXTRAN CAUSES HYPERSENSITIVITY &ANAPHYLAXIS,HENCE NOT

PREFERRED
Noninvasive and Mechanical Methods
• Early mobilization,
• adequate hydration,
• calf exercises,
• graduated stockings (graduated compression stockings maintaining an ankle
pressure gradient of 30–40 mm of Hg. )
• pneumatic compression devices

Graduated compression stockings have been recommended for the following group of patients9:
l Hospitalized patients with contraindication to LMWH
l Post caesarean section while in the hospital (along with LMWH) in those with high risk for VTE
l Patients with previous VTE managed on outpatient basis
l Prolonged travel (.4 hours)
DIAGNOSIS
• Given the potential risks associated with proximal lower extremity
DVT that is not treated (e.g., fatal pulmonary emboli) and the
potential risk of anticoagulating a patient who does not have a DVT
(e.g., fatal bleeding), accurate diagnosis is essential.
• Classic symptoms of DVT include
- swelling,
- pain, and
- discoloration in the involved extremity.
• There is not necessarily a correlation between the location of
symptoms and the site of thrombosis.
• Symptoms in the calf alone are often the presenting manifestation of
significant proximal vein involvement, while some patients with whole
leg symptoms are found to have isolated calf vein DVT.
HISTORY
• A complete thrombosis history includes the age of onset, location of
prior thrombosis, and results of objective diagnostic studies
documenting thrombotic episodes in the patient, as well as in any
family members.
• A positive family history is particularly important, since a well
documented history of venous thrombosis in one or more first-degree
relatives strongly suggests the presence of a hereditary defect.
• Recent potential precipitating conditions
• Underlying conditions: i.e. cancer, collagen-vascular disorders
• Medications
Clinical examination
Special attention should be directed to:
• The vascular system
• Extremities (e.g., looking for signs of superficial or deep vein thrombosis)
• Chest
• Heart
• Abdominal organs
• Skin (e.g., skin necrosis, livedo reticularis).
• There may be pain and tenderness in the thigh along the course of the major
veins ("painful deep vein syndrome").
• Tenderness on deep palpation of the calf muscles is suggestive, but not
diagnostic.
• Homan's sign (unreliable).
DVT Physical Exam
Many patients are asymptomatic; however, the history may include
the following:
• Edema, principally unilateral, is the most specific symptom.
• Massive edema with cyanosis and ischemia (phlegmasia cerulea
dolens) but rare.
• Leg pain occurs in 50% of patients, but this is entirely nonspecific.
• Pain can occur on dorsiflexion of the foot (Homans sign).
DVT Physical Exam
Homan’s sign
• Discomfort in the calf muscles on forced dorsiflexion of the foot with
the knee straight has been a time-honored sign of DVT. However, this
sign is present in less than one third of patients with confirmed DVT.
• The Homan’s sign is found in more than 50% of patients without DVT
and, therefore, is nonspecific.
DVT Physical Exam
-Tenderness occurs in 75% of patients but is also found in 50% of
patients without objectively confirmed DVT.
-Clinical signs and symptoms of PE as the primary manifestation occur
in 10-50% of patients with confirmed DVT.
-The pain and tenderness associated with DVT does not usually
correlate with the size, location, or extent of the thrombus.
-Warmth or erythema of skin can be present over the area of
thrombosis
DVT Physical Exam
• Superficial thrombophlebitis is characterized by the finding of a
palpable, indurated, cordlike, tender, subcutaneous venous segment.
• 40% patients with superficial thrombophlebitis without coexisting
varicose veins and with no other obvious etiology (e.g., intravenous
catheters, intravenous drug abuse, soft tissue injury) have
an associated DVT.
DVT Differential Diagnosis
• Muscle strain, tear, or twisting injury to the leg — 40 percent
• Leg swelling in a paralyzed limb — 9 percent
• Lymphangitis or lymph obstruction — 7 percent
• Venous insufficiency (reflux) — 7 percent
• Baker's cyst — 5 percent
• Cellulitis — 3 percent
• Knee abnormality — 2 percent
• Unknown — 26 percent
INVESTIGATIONS
• Any woman with symptoms and/or signs suggestive of VTE should have objective
testing performed
• expeditiously and treatment with low-molecular-weight heparin (LMWH) given
until the diagnosis is excluded by objective testing, unless treatment is strongly
contraindicated.
• CBC, U&E, LFTs
• Compression duplex Doppler
• Chest X- ray
-may identify other pulmonary disease such as pneumonia, pneumothorax or lobar collapse
• ECG
-T wave inversion (21%), S1Q3T3 pattern (15%) and right bundle branch block
• Blood gases
• Ventilation-perfusion isotope lung scan (V/Q)
• computerised tomography pulmonary angiogram (CTPA)
• Helical or spiral CT scan is regarded superior to V/Q scan
• Arteriography
• CT angiography
• Echocardiogram
• Doppler ultrasound of the iliac vein,
• magnetic resonance venography
• conventional contrast venography
Compression Ultrasonography
The diagnosis of venous thrombosis using compression
ultrasonography is made by the findings such as:
• Abnormal compressibility of the vein
• Abnormal Doppler color flow
• The presence of an echogenic band
• Abnormal change in diameter during the Valsalva maneuver
Duplex-Doppler ultrasound image of an acute superficial
femoral vein thrombosis (labeled "V")

Blue color indicates venous blood flow and red indicates

arterial blood flow (labeled "A"). Echogenic white speckles
are seen in the vein which was non-compressible with the
ultrasound probe.
V/Q SCAN
MANAGEMENT
• Management should involve a multidisciplinary team including senior
physicians, obstetricians and radiologists.
The ‘LEFt rule
The three variables that may improve the diagnostic accuracy of dvt in
pregnancy
• Left leg,
• calf circumference difference of atleast 2 cm [E for edema] and
• first trimester presentation [Ft] – the ‘LEFt rule’).
-a negative score accurately identifies pregnant women in whom the
proportion of confirmed DVT is very low

RCOG 2015
RCOG 2015
VTE
MEDICAL MANAGEMENT
• LMWH
• UNFRACTIONATED HEPARIN
INVASIVE MANAGEMENT
• CATHETER GUIDED THROMBOLYSIS
PE
MEDICAL MANAGEMENT
• LMWH
• UNFRACTIONATED HEPARIN
INVASIVE MANAGEMENT
• IVC FILTER
• CATHETER GUIDED THROMBOLYSIS
• SURGICAL THROMBECTOMY
• ECMO
• the use of the modified Wells score (MWS) in pregnancy as a risk
stratification tool in the diagnosis of PE,they found that a MWS of 6 or
higher was 100% sensitive and 90% specific with a positive predictive
value of 36% for PE on CTPA

RCOG 2015
• The Wells clinical prediction guide quantifies the pretest probability
of DVT.
• The model enables providers to reliably stratify their patients into
high-, moderate-, or low-risk categories.
• Combining this with the results of objective testing greatly simplifies
the clinical workup of patients with suspected DVT.
• The Wells clinical prediction guide incorporates
- risk factors,
- clinical signs, and
- the presence or absence of alternative diagnoses.
Studd v-5
• In clinically suspected DVT or PE, treatment with low-molecular-
weight heparin (LMWH) should be commenced immediately until the
diagnosis is excluded by objective testing, unless treatment is strongly
contraindicated.
RCOG 2015
ACOG 2018
Summary of Recommendations and Conclusions

The following recommendation is based on good and consistent

scientific evidence (Level A):
When signs or symptoms suggest new onset DVT, the recommended
initial diagnostic test is compression ultrasonography of the proximal
veins.

ACOG 2018
The following recommendations and conclusions are based on limited or
inconsistent scientific evidence Level B
In general, the preferred anticoagulants in pregnancy are heparin compounds.
Because of its greater reliability and ease of administration,low-molecular-weight
heparin is recommended rather than unfractionated heparin for prevention and
treatment of VTE within and outside of pregnancy.
< A reasonable approach to minimize postpartum bleeding complications is
resumption of anticoagulation therapy no sooner than 4–6 hours after vaginal
delivery or 6–12 hours after caesarean delivery.
< Because warfarin, low-molecular-weight heparin, and unfractionated heparin do
not accumulate in breast milk and do not induce an anticoagulant effect in the
infant, these anticoagulants are compatible with breastfeeding.

ACOG 2018
The following recommendations are based primarily on consensus and expert opinion
(Level C):
< Women with a history of thrombosis who have not had a complete evaluation of
possible underlying etiologies should be tested for antiphospholipid antibodies and for
inherited thrombophilias.
< Adjusted-dose (therapeutic) anticoagulation is recommended for women with acute
thromboembolism during the current pregnancy or those at high risk of thrombosis,
such as women with a history of recurrent thrombosis or mechanical heart valves.
< When reinstitution of anticoagulation therapy is planned postpartum, pneumatic
compression devices should be left in place until the patient is ambulatory and until
anticoagulation therapy is restarted.
< Every unit should have a protocol for when pregnant women and postpartum women
should have anticoagulant medications held and when women who are receiving
thromboprophylaxis are eligible for neuraxial anesthesia. ACOG 2018
Women receiving anticoagulation therapy may be converted from low-molecular-
weight heparin to the shorter half-life unfractionated heparin in anticipation of
delivery, depending upon the institution’s protocol.
< For women who are receiving prophylactic low molecular- weight heparin,
discontinuation is recommended at least 12 hours before scheduled induction of labor
or cesarean delivery; a 24-hour interval is recommended for patients on an adjusted-
dose regimen.
< Placement of pneumatic compression devices before cesarean delivery is
recommended for all women, and early mobilization is advised after caesarean
delivery.
< Each facility should carefully consider the risk assessment protocols available and
adopt and implement one of them in a systematic way to reduce the incidence of VTE
in pregnancy and the postpartum period.
ACOG 2018
 Departmental protocol-DHGMCH
• Treatment of DVT & pulmonary embolism in pregnancy-
• Anticoagulation- The following approach is generally consistent with the guidelines on
management of VTE in pregnancy published by ACCP(2012), ACOG (2018), the European Society
of Cardiology/European Respiratory Society (2018 and 2019), and the American Society of
Hematology (2018)
• AGENT SELECTION
• Subcutaneous LMWH is preferred over IV UFH or subcutaneous UFH in most patients because it
is easier to use, appears to be more efficacious & has a better safety profile.
• In contrast, IV UFH is preferred in patients who have an elevated risk of bleeding or persistent
hypotension due to pulmonary embolism (PE). This preference is based on clinical experience.
• The rationale is that its short half-life and near complete reversal with protamine are desirable if
the anticoagulant effect needs to be stopped due to bleeding or to perform a procedure.UFH
(either IV or subcutaneous) is preferred over subcutaneous LMWH in patients who have severe
renal failure.
• Direct oral anticoagulants ( DOAC) are avoided since little is known about their safety
Dosing-LMWH
• Anticoagulant activity should be monitored with either intravenous or
subcutaneous unfractionated heparin, but it is controversial when low
molecular weight heparin is being used .Regardless of the regimen,
anticoagulant therapy should continue through the remainder of the
pregnancy.
• Reasonable initial doses of subcutaneous LMWH include dalteparin 200
units/kg once daily or 100 units/kg every 12 hours, tinzaparin 175 units/kg
once daily, or enoxaparin 1 mg/kg every 12 hours .
• It is unclear whether monitoring anticoagulant activity using anti-Xa levels is
beneficial in pregnant females on LMWH .
• If anti-Xa levels are being measured to guide dosing of LMWH, the dose is
titrated to an anti-Xa level of 0.6 to 1.0 IU/mL for twice daily administration
or 1 to 2 IU/mL for once daily administration .
DOSING-UFH
• IV UFH
— Initial dosing of IV UFH consists of an IV UFH bolus of 80 units/kg, followed by a continuous infusion of 18
units/kg per hour.
--The infusion is titrated every six hours to achieve a therapeutic activated partial thromboplastin time
(aPTT), defined as the aPTT that corresponds to an anti-Xa level of 0.3 to 0.7 U. The target aPTT range will be
laboratory-specific. Once the target aPTT level is achieved, it should be rechecked once or twice daily.
• Subcutaneous UFH
— A reasonable initial dose of subcutaneous UFH is 17,500 units every 12 hours.
-The dose is then titrated to achieve a therapeutic aPTT, defined as the aPTT that corresponds to an anti-Xa
level of 0.3 to 0.7 U .
-Many clinicians prefer to begin with IV UFH and then transition to subcutaneous UFH in order to achieve a
rapid therapeutic effect for treatment. The transition is traditionally done after the patient has received IV
UFH for 5 to 10 days
 PREGNANCY,LABOR AND DELIVERY
• Treatment with subcutaneous LMWH should be discontinued at least 24
hours prior to delivery if the delivery time is predictable (eg, induction of
labor, planned cesarean section).
• A period of 24 to 36 hours without anticoagulant therapy may be
undesirable in pregnant females who are at high risk for recurrent VTE (eg,
those with an acute PE or proximal DVT that developed within the past
month). Such patients may benefit from having their subcutaneous LMWH
or subcutaneous UFH switched to IV UFH, which can be discontinued 4 to 6
hours prior to delivery .
• A neuraxial catheter may be placed when the aPTT has returned to normal
• The clinician may be unwilling to tolerate even a short interval without
anticoagulant therapy in rare circumstances, such as a patient with reduced
cardiopulmonary reserve and a recent PE.
• A temporary inferior vena cava (IVC) filter can be inserted in this situation, or
delivery can proceed despite full anticoagulation .
• Delivery despite full anticoagulation may also occur if labor begins
unexpectedly. Many patients who deliver while anticoagulated will not have
excessive intrapartum bleeding.However, anticoagulated patients are at
increased risk for a spinal hematoma if a neuraxial anesthesia catheter is
inserted.Neuraxial anesthesia should not be administered to an anticoagulated
patient
PRETERM DELIVERY
• In cases in which preterm delivery is anticipated (eg, triplets, preterm
rupture of membranes, significant cervical dilation, preeclampsia,
growth restriction), it is common to discontinue subcutaneous LMWH
or subcutaneous UFH at 36 weeks of gestation. IV UFH is then used
instead.
• After delivery — A heparin regimen (subcutaneous LMWH, IV UFH, or
subcutaneous UFH) should be restarted 12 hours after a cesarean
delivery or six hours after a vaginal birth, assuming that significant
bleeding has not occurred.
LONG-TERM ANTICOAGULANT
THERAPY
• Options for long-term anticoagulant therapy include subcutaneous
LMWH, subcutaneous UFH, or an oral vitamin K antagonist (eg,
warfarin).
• If warfarin therapy is chosen, the patient should receive both warfarin
and heparin for at least five days.(bridging)
• The heparin should not be stopped until the international normalized
ratio (INR) has been within therapeutic range (usually 2 to 3) for two
consecutive days.
• Warfarin is considered safe during lactation because it does not
accumulate in breast milk to a substantial degree.Direct oral
anticoagulants should be avoided during breastfeeding .
Thank you