Should children with positive lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I (anti-beta 2 glycoprotein I) antibodies be treated with aspirin (acetylsalicylic acid)?

Aspirin Should Not Be Started After First Positive Laboratory Test in Children

Do not initiate aspirin therapy in children based solely on a single positive test for all three antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I). Confirmation testing at least 12 weeks later is required before considering any treatment, and even then, aspirin is only indicated for specific high-risk scenarios, not for all asymptomatic children with positive antibodies 1, 2.

Why Confirmation Testing is Mandatory

• Transient positivity is extremely common in children. In a large pediatric cohort, 58% of children with initially positive lupus anticoagulant had normal results after a median of 1.9 years, and 38% no longer fulfilled all criteria for lupus anticoagulant after 3.2 years 3.

• Most children with positive antiphospholipid antibodies remain asymptomatic. Among 95 children diagnosed with lupus anticoagulant, 84% were completely asymptomatic at diagnosis, and none of these asymptomatic children subsequently developed bleeding, thrombosis, or autoimmune disease during follow-up 3.

• Antiphospholipid syndrome requires persistent antibody positivity. The diagnostic criteria mandate repeat testing 12 weeks apart to confirm persistence before classifying a patient as having antiphospholipid syndrome 1, 2.

When to Consider Aspirin in Children

Low-dose aspirin (1-5 mg/kg/day, maximum 81 mg daily) should only be considered for asymptomatic children who meet ALL of the following criteria 2:

1. Confirmed persistent positivity on repeat testing at least 12 weeks after the initial test
2. High-risk antibody profile, specifically:
   • Triple positivity (lupus anticoagulant + anticardiolipin + anti-β2-glycoprotein I), OR
   • Isolated lupus anticoagulant positivity
3. Additional risk factors such as:
   • Systemic lupus erythematosus (SLE) diagnosis
   • Autoimmune thrombocytopenia
   • Family history of thrombosis

• For children with SLE and confirmed antiphospholipid antibodies, aspirin provides primary prevention benefit, with significantly fewer thrombotic events compared to no treatment (3/27 vs 4/10 patients developed thrombosis, P=0.03) 4.

• For children with autoimmune thrombocytopenia and positive antiphospholipid antibodies, aspirin prophylaxis reduces thrombotic risk (P=0.01) 4.

Critical Management Algorithm

Step 1: Observe and Retest

• Do not start any treatment after the first positive test 2
• Schedule repeat testing in 12 weeks 1, 2
• Provide anticipatory guidance about avoiding additional thrombotic risk factors (smoking, oral contraceptives in adolescents, prolonged immobilization)

Step 2: If Repeat Testing Confirms Persistence

• Evaluate for underlying autoimmune disease, particularly SLE 5, 6
• Assess for additional thrombotic risk factors
• Consider aspirin ONLY if high-risk profile (triple positive or lupus anticoagulant alone) AND additional risk factors present 2

Step 3: If Thrombosis Occurs

• Immediately escalate to full anticoagulation with UFH or LMWH, not aspirin 1, 2
• Transition to warfarin with target INR 2.0-3.0 for venous thrombosis 1, 2
• Continue anticoagulation for at least 3-12 months depending on whether thrombosis was provoked or unprovoked 1

Important Safety Considerations

• Reye's syndrome risk: Children on aspirin therapy require annual influenza and varicella vaccination, and aspirin must be temporarily stopped during influenza or varicella infections 2.

• Bleeding risk with isolated antibodies: In children presenting with bleeding and positive lupus anticoagulant, the bleeding is typically due to concurrent hypoprothrombinemia or thrombocytopenia, not the antibody itself 3, 7. These children need treatment of the underlying bleeding disorder, not aspirin.

• Thrombosis is rare without persistence: Only 3 of 83 children (4%) in long-term follow-up had persistent positive antibodies, and these were the only ones who developed thrombosis 3. Transient positivity does not confer thrombotic risk.

What NOT to Do

• Do not use warfarin for primary prevention in asymptomatic children with positive antibodies, even if triple positive, as the bleeding risk outweighs benefit without prior thrombosis 1, 8

• Do not use DOACs (rivaroxaban, apixaban) in children with confirmed antiphospholipid syndrome, as rivaroxaban is associated with excess thrombotic events compared to warfarin in triple-positive patients 1

• Do not extrapolate adult dosing: The aspirin dose for antiplatelet effect in children (1-5 mg/kg/day) is substantially lower than anti-inflammatory dosing (80-100 mg/kg/day used in Kawasaki disease) 1, 2