How to manage a child with Antiphospholipid Syndrome (APS)?

Management of Pediatric Antiphospholipid Syndrome

Primary Recommendation

Do not start anticoagulation in asymptomatic children with positive antiphospholipid antibodies, even if triple-positive, unless they have already experienced a thrombotic event. 1

Risk Stratification and Initial Assessment

Antibody Profile Classification

• Triple-positive status (lupus anticoagulant + anticardiolipin antibodies + anti-β2-glycoprotein I antibodies) represents the highest thrombotic risk and requires confirmation on two separate occasions at least 12 weeks apart before making treatment decisions 1, 2
• Moderate-risk antibody titers are defined as ≥40 Units, while high-risk titers are ≥80 Units 2
• Assess for concurrent systemic lupus erythematosus or other autoimmune conditions, as secondary APS requires different management considerations 3, 4

Clinical Presentation Patterns

• Pediatric APS typically presents with large-vessel thrombosis and thrombotic microangiopathy, with more severe presentations than adults including frequent recurrences and higher risk of catastrophic APS 3, 5
• Non-thrombotic manifestations (thrombocytopenia, livedo reticularis, cardiac valve abnormalities, neurological symptoms) are common and may precede thrombotic events 2, 5
• Consult pediatric hematology to exclude other differential thrombophilic conditions 3

Management Algorithm by Clinical Scenario

Asymptomatic Children with Positive Antibodies

No anticoagulation is indicated. 1 Instead:

• Consider low-dose aspirin (1-5 mg/kg per day) for primary thromboprophylaxis only in high-risk situations (triple-positive status with additional cardiovascular risk factors or concurrent autoimmune disease) 1
• The evidence for aspirin in pediatric primary prevention is limited, and bleeding risk must be carefully weighed against potential benefits, as thrombotic risk in children is lower than adults 1
• Avoid direct oral anticoagulants (DOACs) entirely in triple-positive patients due to increased thrombotic events compared to vitamin K antagonists 1, 2

Acute Thrombotic Event Management

Immediate anticoagulation is mandatory. 1, 3 Follow this sequence:

1. Initial phase: Start unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) immediately 1, 3

2. Transition phase: Switch to vitamin K antagonists (warfarin) with target INR 2.0-3.0 for venous thrombosis 1, 2, 3

3. Arterial thrombosis: Consider higher intensity anticoagulation (INR 3.0-4.0) 2

4. Duration: Long-term anticoagulation is required, as pediatric APS has frequent recurrences 3, 4, 5

Critical pitfall: Never use DOACs in triple-positive APS patients—they are associated with increased arterial thrombosis, especially stroke 2, 6

Catastrophic APS

Triple therapy is essential: 3

• Anticoagulation (UFH or LMWH)
• Intravenous corticosteroid pulse therapy
• Plasma exchange
• Consider adding intravenous immunoglobulin 3
• Emerging therapies include eculizumab (complement inhibitor) and sirolimus for refractory cases 3, 5

Special Populations and Considerations

Adolescent Girls

Provide comprehensive counseling: 1

• Contraceptive counseling is essential—avoid estrogen-containing contraceptives due to thrombotic risk 1
• Consider hydroxychloroquine as adjunctive therapy to reduce thrombotic complications 1, 2
• Address lifestyle modifications, treatment adherence, and mental health issues associated with chronic autoimmune thrombophilia 3

Pregnancy in Adolescents with APS

Immediate maternal-fetal medicine consultation is required. 1 Treatment protocol:

• Prophylactic-dose LMWH plus low-dose aspirin (81-100 mg daily) throughout pregnancy for obstetric APS 1, 2
• For thrombotic APS: Therapeutic-dose LMWH plus low-dose aspirin throughout pregnancy and postpartum 2
• Start aspirin before 16 weeks gestation and continue through delivery 2

Neonatal APS (Transplacental Transfer)

• Neonatal APS from maternal antibody transfer rarely causes acute thrombotic events in the perinatal period 5
• More commonly associated with long-term neurodevelopmental abnormalities requiring monitoring 5
• Do not anticoagulate neonates with active bleeding—anticoagulation is contraindicated in active major hemorrhage 7

Adjunctive Therapies

Hydroxychloroquine

• Conditionally recommended for primary APS as it may decrease complications 2
• Consider for refractory APS or as adjunctive therapy in adolescents 1, 2

Statins

• May have a role due to anti-inflammatory and immunomodulatory properties, particularly when cardiovascular risk factors are present 2

Monitoring Requirements

• Regular anticoagulation monitoring with INR for warfarin therapy 2
• Anti-Xa monitoring for patients on LMWH 2
• Serial fibrinogen levels if bleeding complications occur 7
• High-risk profiles (triple-positive or double-positive with lupus anticoagulant) require more intensive monitoring 2

Key Clinical Pitfalls to Avoid

1. Never assume transient antibodies mean no risk—while many healthy children have transient antibodies after infections, true persistent antibodies require 12-week confirmation 2, 8

2. Never use DOACs in triple-positive patients—if already on a DOAC, transition to warfarin immediately 2

3. Never delay anticoagulation after thrombotic events—pediatric APS has higher recurrence rates than adults 3, 5

4. Never overlook non-thrombotic manifestations—they may precede thrombosis and indicate disease activity 5