Received: 7 March 2017 Revised: 9 October 2017 Accepted: 10 October 2017

DOI: 10.1002/pbc.26881

Pediatric
REVIEW Blood &
The American Society of
Cancer Pediatric Hematology/Oncology

Deep vein thrombosis in pediatric patients

Julie Jaffray Guy Young

Children's Hospital Los Angeles, Keck School of

Medicine, University of Southern California, Los
Angeles, California
Correspondence
Julie Jaffray, Children's Hospital Los Ange-
les, Keck School of Medicine, University of
Southern California, 4650 Sunset Blvd., MS
#54, Los Angeles, CA 90027.
Email: jjaffray@chla.usc.edu
Abstract
Due to advances in caring for critically ill children and those with chronic diseases, rates of deep
vein thrombosis (DVT) are increasing in children. Risk factors consist of central venous catheters,
chronic medical conditions, thrombophilia, and various medications. Compression Doppler ultra-
sonography is the method most commonly used to diagnose DVT, and patients will usually present
with pain and swelling of the affected limb. Anticoagulation via subcutaneous injection is the most
common treatment regime for children with DVT, and the new, direct oral anticoagulants are
currently under investigation. Prevention techniques are not established, but clinical studies are
addressing this need.

KEYWORDS
anticoagulation therapy, coagulation thrombolytic, hematology hemostasis and thrombosis,
thrombophilia, thrombosis, thrombotic disorders

1 INTRODUCTION pediatric hematologists/oncologists must have a clear understanding

regarding the epidemiology, diagnosis, treatment, and prognosis of
Deep vein thrombosis (DVT) refers to a blood clot that forms in the this condition. This review aims to discuss the risk factors for the
deep veins of the limbs, thoracoabdominal area, or cerebral sinuses. development of pediatric DVT, the presenting symptoms, diagnostic
Historically, DVT was a condition primarily occurring in adult patients. modalities, available treatment regimens, and long-term sequelae.
Due to the improved care of ill children, and in particular, the signifi-
cant increased use of central venous catheters (CVCs), combined with
improvements in clinical recognition and radiographic techniques, the
rate of DVT in pediatrics is on the rise.1 Patients diagnosed with DVT
2 EPIDEMIOLOGY
have increased mortality (up to 2%)2 and morbidity, which includes the
The majority of cases of venous thrombosis (VTE) occur in children
progression to a pulmonary embolus (PE) and the development of post-
who are or recently were hospitalized. The incidence of HA-VTE,
thrombotic syndrome (PTS).3,4 Due to the increased life expectancy in
which includes DVT and PE, has been steadily increasing.1,5 Data from
children compared with adults, issues surrounding morbidity and long-
the Kids’ Inpatient Database showed that tertiary care centers have
term outcomes take on greater meaning.
increased rates of thrombosis over community hospitals.5
Efforts toward prevention of thrombosis in children are under-
The incidence of thrombosis in children has a bimodal distribu-
way through a collaborative group known as Children's Hospitals’
tion; the highest peak occurs in children less than 1 month of age
Solutions for Patient Safety (CHSPS). This group aims to decrease
at 14.5 per 10,000 children, with the second peak occurring during
10 hospital-acquired (HA) conditions in pediatrics including throm-
adolescence.6,7 The neonatal group represents a unique population of
bosis. Unfortunately, effective prevention techniques for venous
ill neonates, often premature, in whom DVT is overwhelmingly caused
thromboembolism (VTE) have not been established, and rates of
by CVCs. Non-HA DVT occurs most often in children ≥11 years.8
pediatric thrombosis are expected to continue to increase. Therefore,

Abbreviations: ALL, acute lymphoblastic leukemia; aPTT, activated partial thromboplastin

time; CHD, congenital heart disease; CVC, central venous catheter; DOAC, direct oral
3 RISK FACTORS
anticoagulant; DTI, direct thrombin inhibitor; DVT, deep vein thrombosis; HA,
Hospital-acquired; HIT, heparin-induced thrombocytopenia; IBD, inflammatory bowel
disease; INR, international normalized ratio; LMWH, low molecular height heparin; MRV,
3.1 Central venous catheters
magnetic resonance venography; PE, pulmonary embolus; PICC, peripherally inserted central
catheter; PTS, postthrombotic syndrome; UFH, unfractionated heparin; VKA, vitamin K The most common risk factor for DVT in children is the presence
antagonist; VTE, venous thromboembolism of a CVC2,6 (Table 1). Depending on the type of CVC, the patient

Pediatr Blood Cancer. 2018;65:e26881. wileyonlinelibrary.com/journal/pbc 

c 2017 Wiley Periodicals, Inc. 1 of 9
https://doi.org/10.1002/pbc.26881
2 of 9 JAFFRAY AND YOUNG

TA B L E 1 Risk factors for deep vein thrombosis in children

Risk factor Comments

Patient-related
Age Highest risk in children <1 month and ≥11 years2
Thrombophilia Lowest risk for recurrent DVT with factor V Leiden and elevated lipoprotein a14
Anatomic anomalies May-Thurner or Paget–Schroetter syndrome
Hospital-related
Central venous catheters Highest risk in catheters placed in the femoral vein (versus subclavian vein), upper left extremity (versus upper
right) and multilumen10,13,15,16
Prolonged hospitalization Each additional day increases risk by 3%17
Intensive care unit admission Either initial admission to an ICU or transfer17
Surgery DVT diagnosed most commonly after cardiac surgery18
Trauma Trauma requiring ICU admission19
Immobility Immobilization for >72 hr20
Disease-related
Infection/inflammation Highest risk with systemic blood stream infection20,21
Cancer Highest risk for patients with leukemia, lymphoma, and sarcoma over brain tumors22
Congenital heart disease Patients have abnormal levels and function of pro- and anticoagulant proteins23
Intestinal failure Highest risk seen in patients with CVCs and parental nutrition24
Neuromuscular diseases Increased risk due to immobility18
Nephrotic syndrome Due to urinary loss of anticoagulants, mostly antithrombin25
Medications
Asparaginase Reduces levels of antithrombin, protein C, and protein S26
Steroids Increases and decreases the levels of many pro- and anticoagulant proteins26
Estrogen Increases the levels of many pro-coagulant and decreases many anticoagulant proteins27,28

DVT, deep vein thrombosis; ICU, intensive care unit.

population and the imaging technique, DVT rates range from 2.6–34%
in children.9–13 This is in all likelihood due to the vascular injury caused
by insertion of the catheter as well as the abnormal flow that occurs
when a catheter sits in the vessel lumen.
There are different types of CVCs including nontunneled (percuta-
neous) femoral and internal jugular CVCs, peripherally inserted central
catheters (PICCs), or tunneled CVCs, such as implanted subcutaneous
ports or external catheters. Studies are contradictory as to which type
of CVC, insertion technique, or catheter material has the highest risk
for DVT development. A meta-analysis found that DVT rates were low-
est in patients who had PICCs and umbilical lines (versus tunneled
lines), without a difference in DVT rates between CVCs placed in the
upper or lower extremity.14 Conversely, a systematic review found tun-
neled lines (versus nontunneled and PICCs) to have the lowest rate of
DVT.15
The inconsistencies above are likely due to the retrospective study
designs, the various patient populations, and whether the endpoint
was symptomatic DVT or asymptomatic VTE, that is, captured by
surveillance imaging.
3.2 Disease-related
Hospitalized children are at the greatest risk of developing DVT
due to the presence of multiple risk factors they acquire including
the aforementioned use of CVC, as well as immobility, inflammation,
infection, surgery, etc.5,16–20 Acutely ill children admitted to the hospi-
tal have an increased risk of thrombosis of 3% for every additional day
of hospitalization.16
Malignancy and congenital heart disease (CHD) are the two chronic
diseases with the highest risk for DVT. Children with cancer have
reported rates of DVT of 7–34%.8,9,13,21 This is due to several reasons,
including the cancer itself,22 as well as chemotherapeutic agents such
as steroids and asparaginase, the frequent use of CVCs, and infection.
Studies have also shown higher rates of thrombosis in older children
with cancer and those with metastatic disease.23
Patients with CHD are at the highest risk for thrombosis when they
are critically ill, postsurgical, have a CVC in place and have a single ven-
tricle physiology. These children have been found to have abnormal-
ities in the function of their coagulation proteins and blood flow and
issues with blood vessel wall integrity.24 In addition, children requir-
ing mechanical circulatory support have increased thrombosis risk due
to the low-flow state of the devices and their pro-thrombotic circuit
material.25,26
Other chronic diseases that increase DVT frequency in children
are gastrointestinal failure leading to long-term total parenteral nutri-
tion, inflammatory bowel disease (IBD), and children with renal fail-
ure on dialysis.27 Patients with IBD have an increased thrombosis
risk due to increased inflammatory cytokines, upregulation of tis-
sue factor, and impaired fibrinolysis.28 Diseases that cause immobil-
ity, such as spina bifida and quadriplegia have also been shown to
JAFFRAY AND YOUNG 3 of 9

lead to increased DVT incidence due to increased venous stasis from

inactivity.29

3.3 Thrombophilia
Inherited and acquired thrombophilia have been linked with increased
onset and recurrence of thrombosis in children and adults.30 The
thrombophilias most often tested include the prothrombin G20210A
and Factor V Leiden gene mutations; decreased proteins C, S, and
antithrombin; elevated lipoprotein (a), homocysteine and factor VIII;
and antiphospholipid antibodies. Adult guidelines recommend against
routine thrombophilia testing, but studies have shown testing could be
beneficial in children.
In a healthy child with a known thrombophilia, without another risk
factor for DVT, the risk for thrombosis is low.31 In children with a F I G U R E 1 Infant with superior vena cava (SVC) syndrome showing

known risk factor, such as cancer, the additive risk of thrombophilia signs of skin discoloration and swelling of the upper chest, neck and
head
may be significant.32,33 Thrombophilia testing should be performed
Note: Received informed consent to use this photo.
in cases where the VTE was unprovoked, in patients with recurrent
VTE, and in those with a strong family history of thrombosis. For other
patients, the benefits of testing are less clear. symptoms present in various ways. For example, an extremity DVT will
typically cause swelling and pain, and occasionally warmth or discol-
3.4 Medications oration of the skin of the affected limb. DVT in the superior vena cava
(SVC) can result in SVC syndrome, which leads to skin discoloration,
Oral contraceptives are known to increase the risk of DVT, especially
pain and swelling of the upper chest, neck and head (Fig. 1). Abdomi-
in the first year of initiating therapy by altering the nature of the coag-
nal DVTs are more challenging to identify and diagnose as symptoms
ulation and fibrinolytic system. These alterations include increasing
are frequently absent or nonspecific. These symptoms are also due to
levels of prothrombin, factor VII, factor VIII, factor X, von Willebrand
venous obstruction and lead to swelling and pain of the affected area
factor, and fibrinogen, as well as acquired resistance to activated pro-
that can be manifested, for example, as left upper quadrant pain due to
tein C and increased fibrinolytic activity.34 The estrogen component
an engorged spleen in the setting of splenic vein thrombosis. Throm-
also leads to decreased protein C, protein S, and antithrombin levels.35
bosis in the portal vein is important to identify because it can lead to
Studies have also shown that third-generation progestins may give
portal hypertension with resultant splenomegaly and upper gastroin-
additive thrombosis risk.
testinal bleeding, which can paradoxically even be the presenting signs
Asparaginase, one of the key chemotherapeutic agents used in chil-
of the DVT. Renal vein thrombosis can cause renal function impair-
dren with acute lymphoblastic leukemia (ALL), causes inhibition of
ment as well as hematuria. Signs of cerebral sinus venous thrombosis
coagulation protein synthesis. This inhibition can lead to an increased
can be acute headache, vomiting, visual impairment, focal neurological
risk of thrombosis and hemorrhage, although the risk is usually more
impairment, and seizures.
thrombotic due to the reduction of the anticoagulants, antithrombin,
A more subtle symptom of catheter-related VTE is catheter mal-
protein C, and protein S.36 Corticosteroids, which are also part of the
function resulting in difficulty with infusing medications or drawing
backbone in ALL therapy, are used in many other malignant and non-
blood samples. This symptom should be a signal to consider diagnostic
malignant diseases. Prednisone has been shown to increase levels of
imaging. Children with a CVC in place, especially those acutely ill and
factor VIII, von Willebrand factor, prothrombin and antithrombin, and
hospitalized, should be monitored daily for DVT symptoms. Another
decreases in fibrinogen and plasminogen.36
subtle symptom is thrombocytopenia, which can be a sign of thrombo-
Other drugs that have been shown to increase the risk for throm-
sis in neonates and infants.
bosis are activated prothrombin complex concentrates, some antipsy-
chotics, all-trans-retinoic acid, many chemotherapeutic agents such as
bevacizumab, doxorubicin, lenalidomide, thalidomide as well as some
immunosuppressive agents and thienopyridine derivatives.37 5 DIAGNOSIS

5.1 Imaging

4 CLINICAL SYMPTOMS Compression, Doppler ultrasonography is the most common method

for diagnosing DVT. It utilizes three approaches to identifying a clot—
The symptoms of DVT are the result of an obstruction to venous out- direct visualization, compression, and color Doppler flow. It is espe-
flow and the resultant venous hypertension that occurs in the area cially useful in the extremities, and has been shown to have >95%
drained by the obstructed vein. Depending on the location, these specificity in the proximal deep veins of the lower extremity in adults.38
4 of 9
Caution must be exercised in the upper extremity as the sensitiv-
ity is lower and a negative ultrasound does not exclude DVT.39 His-
torically venography is the gold standard, and it is still highly use-
ful for assessing the extremities or thoracoabdominal region if an
ultrasound is negative. More recently, the use of both magnetic reso-
nance venography (MRV) and computed tomography venography has
replaced traditional venography as the primary imaging tool for the
abdomen and chest. In addition, MRV is the preferred method to diag-
nose cerebral sinus venous thrombosis. To detect anatomical defects
of the upper extremity such as Paget–Schroetter syndrome, or lower
extremity such as May-Thurner syndrome, compression ultrasonog-
raphy followed by confirmatory testing with contrast venography or
MRV should be performed.
5.2 Laboratory
There are few laboratory tests that can aid in diagnosing DVT. The D-
dimer, which is a marker of fibrinolysis, is often elevated in patients
with thrombosis and may raise the suspicion of DVT but cannot be used
to diagnose DVT. In adult patients, the D-dimer has a strong negative
predictive value and is recommended to be performed in patients with
clinical suspicion for DVT prior to ordering radiographic imaging.40
Evaluation of the D-dimer in children to predict thrombosis revealed
the test to be sensitive but only moderately specific.41 Abnormal renal
and liver function testing can be seen with hepatic, portal, and renal
vein thrombosis.
6 TREATMENT
In children, anticoagulation is the treatment of choice for DVT unless
there is a contraindication such as active or significant risk for bleeding
(Table 2).42 Anticoagulation is initiated to prevent thrombus extension
and embolization to the lungs or rarely the brain in patients with right
to left shunting. Recommendations for dosing, monitoring, and treat-
ment length are primarily based on extrapolated data from the adult
population. This can be exceptionally difficult when treating neonates
and infants where the coagulation system is continuously changing and
developing.
Based on limited evidence, the CHEST guidelines suggest antico-
agulation treatment of 6 weeks to 3 months for patients with a VTE
secondary to an identified and resolved risk factor (such as a CVC),
and a longer duration of 6–12 months for children with an unidenti-
fied risk factor.42 Kids-DOTT, a randomized controlled trial to assess
the duration of anticoagulation therapy in children with a new VTE sec-
ondary to a transient or reversible risk factor, is underway to improve
on this paucity of treatment duration data in the pediatric population
(NCT00687882).43
6.1 Unfractionated heparin
Unfractionated heparin (UFH) is administered via continuous intra-
venous infusion, and provides anticoagulation by inactivating throm-
bin and activated factor X by potentiating the effects of antithrombin.
JAFFRAY AND YOUNG
Benefits include a short half-life and the availability of a reversal agent,
protamine, which can be used in cases of hemorrhage. Increased dos-
ing is needed in neonates due to decreased levels of antithrombin, and
in children less than 1 year of age due to increased heparin binding
to non-antithrombin proteins. UFH can be monitored using the acti-
vated thromboplastin time (activated partial thromboplastin [aPTT])
or antifactor Xa assay, although studies have shown increased time in
the therapeutic range when using the antifactor Xa assay.44 Heparin-
induced thrombocytopenia (HIT) is a rare, but serious side effect, which
occurs in 1–2% of children exposed to heparin due to the development
of antibodies against platelet factor 4/heparin complex.45 Treatment
includes stopping all heparin products and starting a nonheparin anti-
coagulant.
6.2 Low molecular weight heparins
The low molecular weight heparins (LMWHs), which consist of enoxa-
parin, dalteparin, tinzaparin, and nadroparin, are the anticoagulants
most commonly prescribed in children. As they are byproducts of hep-
arin, they also exert their anticoagulant effect via antithrombin, how-
ever they are more targeted at activated factor X. They have been
shown to be as efficacious as UFH with less bleeding complications and
episodes of HIT.46 In children, LMWHs are typically given twice daily as
a subcutaneous injection and are monitored by the antifactor Xa assay.
Studies in adult patients have shown that once-daily LMWH dosing is
safe and efficacious to treat DVT, but pharmacodynamic (PD) studies
in children to support the feasibility of this dosing regime have been
conflicting.47,48 Long-term use of LMWH can lead to osteopenia.49
6.3 Parenteral direct thrombin inhibitors
Bivalirudin is a direct thrombin inhibitor (DTI), which blocks the effects
of thrombin, such as fibrin generation and platelet activation.50 Unlike
UFH and LMWH, it does not require antithrombin to be effective.
Bivalirudin is given via continuous infusion and can be used to treat
VTE or HIT. Levels can be monitored by the aPTT, however a recent
publication suggests no drug monitoring.51 There is evidence that
bivalirudin facilitates early clot regression and resolution.51 Arga-
troban, another DTI given by continuous intravenous infusion, is most
often used in children suspected or diagnosed with or at risk for HIT.52
Argatroban is hepatically cleared via CYP3A4/5, bivalirudin is par-
tially cleared via the kidneys, and the remainder undergoes intracellu-
lar proteolysis.53,54
6.4 Fondaparinux
Fondaparinux is a synthetic pentasaccharide, which is a selective
antithrombin-dependent factor Xa inhibitor.55 It is administered
through a once-daily subcutaneous injection and can be used to treat
VTE or HIT. Monitoring is via an antifactor Xa assay that is calibrated
for fondaparinux. Pediatric studies have demonstrated efficacy and
safety and provide dosing guidelines.56
JAFFRAY AND YOUNG
TA B L E 2 Anticoagulant treatment dosing and monitoring for children diagnosed with a deep vein thrombosis
Anticoagulant Dose
UFH 28 units/kg/hr (age <1 year)
20 units/kg/hr (age ≥1 year)
LMWH 1.5 mg/kg/dose (age <2 months)
1 mg/kg/dose (age >2 months)
Bivalirudin 0.125 mg/kg/hr
Argatroban 1 𝜇g/kg/min
0.1 mg/kg/day
Fondaparinux
VKA 0.1 mg/kg/day
DOACs Not determined in children
UFH, unfractionated heparin; aPTT, activated partial thromboplastin time; LMWH, low molecular weight heparin; VKA, vitamin K antagonist; INR, interna-
tionalized ratio; DOACs, direct oral anticoagulants.
6.5 Vitamin K antagonists
Warfarin, the most commonly used vitamin K antagonists (VKAs),
exerts its anticoagulant effect by inhibiting the gammacarboxylation,
and thus activation, of the vitamin K dependent coagulation factors II,
VII, IX, and X. Warfarin can be given orally once daily, but has numer-
ous drug and food interactions. Anticoagulant effect is measured using
an international normalized ratio (INR). When initiating VKA, they
must be given alongside another anticoagulant for at least 5 days and
until a therapeutic INR is achieved to avoid transient hypercoagula-
bility due to a decrease in proteins C and S, which are also vitamin K
dependent.
6.6 Direct oral anticoagulants
There are two classes of direct oral anticoagulants (DOACs), the DTI,
dabigatran, and the direct factor Xa inhibitors, rivaroxaban, edoxaban,
and apixaban. In adults, the DOACs are approved for VTE treatment,
VTE prevention, and stroke prevention due to nonvalvular atrial fibril-
lation. Studies have found the DOACs to have comparable efficacy to
VKAs, but with significantly lower risk of bleeding.57
The DOACs, which are yet to be approved for use in children less
than 18 years, may allow children to receive anticoagulation with-
out injections or numerous laboratory tests. Phase I pharmacokinetic
and PD (PK/PD) as well as phase II studies have been completed
for rivaroxaban and dabigatran.58,59 PK/PD studies for apixaban and
edoxaban continue to recruit patients.60,61 Pediatric phase III trials
comparing each DOAC to standard anticoagulation (LMWH, fonda-
parinux, or VKAs) are open and recruiting for rivaroxaban, edoxaban,
and dabigatran.62,63 A phase III randomized study is evaluating the
safety and efficacy of apixaban to prevent thrombosis in children with
newly diagnosed ALL treated with asparaginase.64
Dosing is orally once or twice daily (depending on the medication)
without any necessary laboratory monitoring. A dabigatran reversal
agent, idarucizumab, has been approved for use in adults and andex-
anet, a reversal agent for factor Xa inhibitors, is still undergoing inves-
tigation.
5 of 9
Route of administration and
frequency Monitoring
Intravenous, bolus then Antifactor Xa assay or
continuous infusion aPTT
Subcutaneous injection, twice Antifactor Xa assay
daily
Intravenous, bolus then aPTT
continuous infusion
Intravenous, continuous infusion aPTT
Subcutaneous injection, once Factor Xa assay
daily
Oral, once daily INR
Oral once or twice daily Unknown at this time
6.7 Thrombolysis
A more aggressive treatment approach for the management of DVT
involves thrombolysis. Thrombolysis can be given systemically or
via a catheter-directed approach. Protocols in children have been
established using both high- and low-dose systemic thrombolysis
regimes, usually with concurrent anticoagulation and close monitoring
for bleeding.65,66 Catheter-directed thrombolysis involves placing
a large bore catheter into the vein affected by the DVT to allow a
slow, direct infusion of the thrombolytic agent onto the thrombus.67
Tissue plasminogen activator (alteplase) is the main thrombolytic
agent used for either catheter-directed or systemic thrombolysis. In
pediatrics, thrombolysis is usually reserved for patients with severe
limb-threatening or life-threatening thrombosis, but the frequency
of use in children is increasing, and it should be considered especially
in children with nonprovoked large DVTs of the lower extremity.
Small studies demonstrated that this approach is more effective than
anticoagulation in preventing PTS.68 A randomized controlled trial will
be opening to evaluate the efficacy of catheter-directed thrombolysis
followed by anticoagulation versus anticoagulation alone in children
with proximal leg DVT (NCT02767232).
7 LONG-TERM SEQUELAE
The main long-term sequelae for DVT are recurrence and PTS. Local
recurrence or second thrombotic episodes in children range from 7%
to 21% depending on patient age, presence of thrombophilia, or pro-
voking agent (such as a CVC).2,6,30,69 PTS is due to venous insufficiency
resulting from valvular damage, and leads to chronic pain and swelling,
tingling, reduced exercise tolerance, and in severe cases skin ulcera-
tion (Fig. 2). PTS has been found in up to 63% of children diagnosed
with DVT, especially in those with multiple vein segments involved and
lack of radiographic DVT resolution.70,71 Patients who developed an
upper extremity DVT due to overuse (sports, weight lifting, musical
instrument playing) are more likely to develop PTS versus CVC-related
DVTs.72 Lack of DVT resolution or extension of the thrombosis is also a
6 of 9
F I G U R E 2 Severe postthrombotic syndrome (PTS) in an adolescent
patient leading to skin ulceration
Note: Received informed consent to use this photo.
predictor of PTS in upper extremity DVT.72 Techniques to prevent PTS
have not been established in adult or pediatric patients, although some
find compression stockings to improve symptoms.
8 PREVENTION
Prophylactic techniques have yet to be deemed effective in children. In
adults, mechanical and pharmacological prophylaxis, especially when
used in combination, has been shown to decrease the rate of VTE.73,74
Mechanical prophylaxis refers to either intermittent pneumatic com-
pression devices or graduated compression stockings, both of which
use pressure to improve lower limb venous circulation. Pharmaco-
logical prophylaxis consists of anticoagulation, usually at doses lower
than those used for treatment. Randomized controlled trials have been
performed in children aimed at preventing VTE using prophylactic
UFH, LMWH, or warfarin.75–78 One of the four trials, which included
severely ill trauma patients, found a difference in thrombosis rates
between the treatment groups. The other three trials focused on pre-
vention of CVC-associated thrombosis and did not demonstrate anti-
coagulation to be effective.
To determine which patients require VTE prevention, their risk for
VTE must be determined. Pediatric specific VTE risk prediction mod-
els have been created, although most are either single-institution stud-
ies or for specific patient populations. Raffini et al. developed a risk
prediction model to prevent HA non-CVC-related VTE in adolescents
and Mitchell et al. created a model to predict risk in children with
ALL.79,80 Three single-institution studies created models to predict
HA-VTE and were validated retrospectively; the highest risk variables
included infection, prolonged hospitalization, immobilization, and the
presence of a CVC.17,18,81
Further studies in this area are clearly needed, and the multi-
institutional Children's Hospital Acquired Thrombosis (CHAT) study
is currently under way aiming to identify risk factors, create a risk
prediction model, and determine thrombosis prevention strategies for
hospitalized children at risk for thrombosis.82,83
JAFFRAY AND YOUNG
9 DISCUSSION
A strong understanding of DVT in children is imperative for clinicians
managing such patients. Increased efforts should be made to evaluate
for DVT in all children with a CVC in place; assessment of line func-
tion or limb swelling should be made daily while inpatient and at every
ambulatory visit. In children without a CVC, the consideration of DVT
should be made for any child who presents with a painful and swollen
limb, especially in high-risk populations, such as those with cancer or
CHD, or an adolescent female recently started on oral contraception.
Due to the overall low incidence of DVT in the outpatient setting in
pediatrics, delays in the diagnosis are not uncommon.
Pediatric DVT risk prediction and prevention techniques are also
being studied.79,81–83 Ideally, once successful strategies have been
identified, the rates of thrombosis in children will decline. At the
moment much work is needed in the pediatric thrombosis community,
and all pediatric clinicians, especially hematologists/oncologists should
stay alert to the changing landscape.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interest.
ORCID
Julie Jaffray http://orcid.org/0000-0002-1175-7266
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How to cite this article: Jaffray J, Young G. Deep vein thrombo-
sis in pediatric patients. Pediatr Blood Cancer. 2018;65:e26881.
https://doi.org/10.1002/pbc.26881