What is venous thrombosis in a 5‑month‑old infant and how should it be treated?

Venous Thrombosis in a 5-Month-Old Infant

Anticoagulation with low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) should be initiated immediately for symptomatic venous thrombosis in a 5-month-old infant, as venous thromboembolism in this age group is almost always associated with serious underlying illness or central venous access devices and requires prompt treatment to prevent life-threatening complications. 1

What is Venous Thrombosis in Infants?

Venous thromboembolism (VTE) in a 5-month-old represents blood clot formation within the venous system, most commonly presenting as deep vein thrombosis (DVT) or, less frequently, pulmonary embolism (PE). 1

Key epidemiologic features:

• Population incidence is extremely low at 0.07-0.14 per 10,000 children, but increases 100-1000 times in hospitalized infants to at least 106 per 10,000 admissions 1
• VTE should be considered a disease of sick children rather than healthy infants 1
• Central venous access devices (CVADs) are implicated in 80-90% of neonatal VTE cases 1

Common presentations in this age group:

• Limb swelling (unilateral extremity edema) 2
• Renal vein thrombosis presenting with gross hematuria, flank mass, and thrombocytopenia 3
• Superior vena cava syndrome if upper extremity/central catheter-related 4
• Repeated catheter obstructions 4

Treatment Algorithm

Immediate Management (First 24 Hours)

For symptomatic DVT or PE, anticoagulation must be started immediately - the American Society of Hematology provides a strong recommendation for anticoagulation over no anticoagulation despite very low certainty evidence, based on strong indirect evidence from adults and the high-risk nature of hospitalized children. 1

Initial anticoagulant options:

• Low-molecular-weight heparin (LMWH): Enoxaparin 1.0 mg/kg subcutaneously every 12 hours, adjusted to maintain anti-factor Xa levels between 0.5-1.0 units/mL measured 4 hours post-injection 5
• Unfractionated heparin (UFH): Intravenous administration with monitoring 1
• Monitor anti-Xa levels twice weekly after initial dose adjustment 5

Site-Specific Considerations

Renal vein thrombosis (RVT):

• High-risk presentations requiring anticoagulation: bilateral thrombosis threatening anuria, unilateral with IVC extension 1
• Supportive care includes correction of fluid/electrolyte disturbances and treatment of underlying pathophysiology 3
• Surgery rarely indicated unless bilateral involvement with IVC compromise 3

Central venous catheter-associated thrombosis:

• Median time from catheter insertion to DVT diagnosis is 19 days (range 7-210 days) 4
• CVAD removal should be considered for complications, though anticoagulation can be continued with catheter in situ if still needed 1

Duration of Anticoagulation

Minimum treatment duration is 3 months for most pediatric VTE, with consideration for extension to 6 months if thrombus persists or complications develop. 5

Critical Diagnostic Workup

Imaging confirmation:

• Duplex ultrasonography with Doppler is the first-line diagnostic test and can be performed readily in the emergency setting 3, 2
• Renal venography remains gold standard for RVT diagnosis 3

Mandatory laboratory evaluation:

• Complete blood count (looking for thrombocytopenia, polycythemia) 3
• Urinalysis (hematuria, proteinuria) 3
• Blood cultures (bacteremia, particularly MRSA, can cause DVT) 2
• Comprehensive thrombophilia panel should be obtained but not during acute anticoagulation to avoid falsely altered results 6

Thrombophilia screening (after acute phase):

• Protein C, protein S, antithrombin III 6, 7
• Factor V Leiden mutation 6, 7
• Prothrombin G20210A mutation 6
• Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-beta-2-glycoprotein I) 6
• Factor VIII levels 6

Common Pitfalls and Caveats

Do not delay anticoagulation while awaiting thrombophilia results - treatment should begin immediately upon diagnosis of symptomatic thrombosis. 1

Avoid testing coagulation inhibitors during acute anticoagulation - protein C, protein S, and antithrombin may be falsely reduced during heparin or warfarin therapy. 6

Direct oral anticoagulants (DOACs) are now an option - the 2024 updated guidelines include rivaroxaban and dabigatran as treatment options for pediatric VTE, representing a major shift from the 2018 guidelines when DOACs were considered investigational. 1 However, DOACs should not be used if antiphospholipid antibodies are confirmed, as they are associated with excess thrombotic events compared to warfarin. 5

Recognize that asymptomatic thrombosis may not require treatment - the natural history remains unclear, and risk-benefit assessment is needed, though this is beyond the scope of acute symptomatic presentations. 1

Family history matters - a positive family history of thromboembolic episodes at young age was found in 30% of children with catheter-related DVT. 4

Bacteremia can cause thrombosis - always obtain blood cultures, as MRSA and other pathogens can precipitate DVT and require concurrent antibiotic therapy. 2