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Venous thromboembolism in children

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The American Society of Hematology (ASH) and the International Society on Thrombosis and Haemostasis (ISTH) have published an updated guideline for the treatment of venous thromboembolism (VTE) in children. Anticoagulation is recommended for symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE), and may be considered for clinically unsuspected DVT or PE. Direct oral anticoagulants (rivaroxaban or dabigatran) are preferred over standard agents, including low molecular weight heparin (LMWH), unfractionated heparin (UFH), vitamin K antagonists (VKA), and fondaparinux. In selected patients with provoked VTE, a 6-week course is favored over 3 months, while for unprovoked VTE, 6-12 months is favored over indefinite therapy. Thrombolysis followed by anticoagulation is suggested only for PE with hemodynamic compromise. .

Background

Overview

Definition
VTE in children refers to thrombotic occlusion of the venous circulation, most commonly manifesting as DVT or PE, and is typically associated with identifiable clinical risk factors.
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Pathophysiology
The pathogenesis of VTE in children follows the principles of Virchow's triad: venous stasis, endothelial injury, and a hypercoagulable state. Pediatric VTE is most often provoked, with over 90% of cases associated with identifiable risk factors. Central venous catheters are the predominant contributor to venous stasis and endothelial trauma, implicated in over half of pediatric DVT cases and the vast majority of neonatal events. Other clinical settings associated with catheter-related thrombosis include malignancy, congenital heart disease, and critical illness. The hypercoagulable state in children may be inherited or acquired. Mild inherited thrombophilic conditions such as factor V Leiden and prothrombin G20210A mutations are relatively common in white populations, whereas severe deficiencies in natural anticoagulants (antithrombin, protein C, and protein S) are rare. Acquired hypercoagulability may occur during systemic infections, inflammation, or sepsis, often marked by elevated factor VIII activity or consumption of anticoagulants in DIC. Antiphospholipid antibodies, usually transient and parainfectious in origin, also contribute to thrombosis risk. In adolescents, the addition of estrogen-containing oral contraceptives to underlying thrombophilia significantly amplifies VTE risk, especially in individuals with concurrent genetic predispositions.
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Epidemiology
The incidence of pediatric VTE has been steadily increasing, with estimates ranging from 0.07 to 0.49 per 10,000 children annually, rising to 4.9-21.9 per 10,000 among hospitalized children (1 in 200 pediatric admissions). Incidence follows a bimodal distribution: neonates account for up to 20% of cases, with rates up to 14.5 per 10,000 in the first month, and adolescents (11-18 years) account for ~50%, with rates reaching 1.1 per 10,000 in ages 15-17. Most cases are provoked, linked to central venous catheters, hospitalization, or comorbidities; idiopathic events are rare. Hospital-associated VTE has risen sharply, from 0.3 to nearly 60 per 10,000 admissions in tertiary centers, especially among ICU patients with prolonged stays and central venous catheters.
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Risk factors
Major risk factors include central venous catheter use, congenital heart disease, malignancy, surgery, trauma, immobility, infection, inflammtory bowel disease, obesity, nephrotic syndrome, autoimmune disorders, inherited or acquired thrombophilia, and use of hormonal therapy. Hospitalization, particularly in ICUs, significantly increases the risk.
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Disease course
The presentation of VTE in children varies by the anatomical site of thrombosis, the degree of vascular occlusion, and the acuity of the event. Acute extremity DVT typically presents with painful, unilateral limb swelling. In upper extremity DVT involving the superior vena cava, children may show facial or neck swelling, bilateral periorbital edema, or headache. PE, although sometimes silent, can manifest with sudden dyspnea, pleuritic chest pain, hypoxemia, and, in severe cases, cyanosis or cardiovascular collapse. Cerebral sinus venous thrombosis often presents with persistent headache, visual changes, seizures, or focal neurological deficits. Renal vein thrombosis, common in neonates, presents with hematuria, thrombocytopenia, and a flank mass. In older children, it is frequently associated with nephrotic syndrome. Portal vein thrombosis may cause splenomegaly, thrombocytopenia, and signs of portal hypertension, including gastrointestinal bleeding. Thrombosis of the internal jugular vein can present with neck pain and swelling, and in Lemierre syndrome, is associated with fever and trismus. Intracardiac thrombi, particularly in the context of central venous catheters or cardiac surgery, are often asymptomatic. Chronic VTE may present incidentally or with features of post-thrombotic syndrome, including persistent limb swelling, pain, dilated superficial veins, skin discoloration, or ulceration.
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Prognosis and risk of recurrence
VTE in children is associated with a moderate risk of recurrence, estimated at approximately 10% overall and around 3% in neonates. Recurrence is more likely in patients with underlying comorbidities such as malignancy, CVD, or neurovascular disorders, as well as those with inherited thrombophilias including prothrombin gene mutation or antithrombin deficiency.Post-thrombotic syndrome is less common and severe in children than in adults, with a reported incidence of approximately 12.4%, though this is likely underestimated due to limited long-term follow-up data. VTE in children is also associated with increased overall mortality. Reported mortality rates range from 9% to 17%, with VTE-specific mortality estimated between 1.5% and 2.2%. The highest mortality is observed in neonates, and a significant proportion of deaths occur within 30 days of diagnosis. While PE is a serious complication, the risk of fatal PE in children is lower than in adults.
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Guidelines

Key sources

The following summarized guidelines for the evaluation and management of venous thromboembolism in children are prepared by our editorial team based on guidelines from the International Society on Thrombosis and Haemostasis (ISTH/ASH 2025), the International Initiative on Thrombosis and Cancer (ITAC 2022), the British Society for Haematology (BSH 2021,2011), and the American College of Chest Physicians (ACCP 2012).
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Diagnostic investigations

Diagnostic imaging, upper limb: as per BSH 2011 guidelines, obtain ultrasound for the initial assessment of the peripheral upper limb, axillary, subclavian, and internal jugular veins, recognizing its relative insensitivity for detecting central intra-thoracic VTE.
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  • Diagnostic imaging (lower limb)

  • Diagnostic imaging (PE)

  • Laboratory tests

  • Testing for inherited thrombophilia

Medical management

General principles: as per ACCP 2012 guidelines, consider involving pediatric hematologists with experience in thromboembolism to manage pediatric patients with thromboembolism when possible. Consider involving a combination of a neonatologist or pediatrician and an adult hematologist, supported by consultation with an experienced pediatric hematologist, if the former is not feasible.
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  • Anticoagulant therapy (indications)

  • Anticoagulant therapy (choice of agent)

  • Anticoagulant therapy (duration)

  • Anticoagulant therapy (recurrent VTE)

  • Thrombolytic therapy

Therapeutic procedures

IVC filter placement: as per ACCP 2012 guidelines, consider inserting a retrievable IVC filter in pediatric patients with body weight > 10 kg who have lower extremity VTE and a contraindication to anticoagulation.
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  • Thrombectomy

Specific circumstances

Patients undergoing hemodialysis: as per ACCP 2012 guidelines, consider administering VKAs or LMWH routinely for fistula thromboprophylaxis in patients undergoing hemodialysis via an arteriovenous fistula.
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  • Patients with purpura fulminans (evaluation)

  • Patients with purpura fulminans (management)

  • Patients with central venous catheter-related thrombosis (prevention)

  • Patients with central venous catheter-related thrombosis (evaluation)

  • Patients with central venous catheter-related thrombosis (catheter removal)

  • Patients with central venous catheter-related thrombosis (anticoagulant therapy)

  • Patients with central venous catheter-related thrombosis (thrombolytic therapy)

  • Patients with cerebral sunus venous thrombosis (prevention)

  • Patients with cerebral sunus venous thrombosis (evaluation)

  • Patients with cerebral sunus venous thrombosis (management)

  • Patients with right atrial thrombosis

  • Patients after cardiac surgery

  • Patients with ventricular assist devices

  • Patients with cardiomyopathy

  • Patients with pulmonary hypertension

  • Patients with structural venous abnormalities

  • Patients with Kawasaki disease

  • Patients with renal vein thrombosis

  • Patients with portal vein thrombosis

  • Patients with superficial vein thrombosis

  • Patients with cancer-related thrombosis

Preventative measures

Thromboprophylaxis: as per BSH 2011 guidelines, consider using physical methods for VTE risk reduction in older children and adolescents at increased risk of VTE.
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