What is the management of Antiphospholipid (APLA) syndrome?

Management of Antiphospholipid Syndrome (APLA)

Long-term anticoagulation with vitamin K antagonists (warfarin) is the cornerstone of therapy for thrombotic antiphospholipid syndrome, with intensity of anticoagulation determined by the type of thrombotic event. 1, 2

Diagnosis and Initial Assessment

• Diagnosis requires both clinical manifestations (thrombosis or pregnancy morbidity) and persistently positive antiphospholipid antibodies (aPL)
• Three main types of aPL to test for:
  • Lupus anticoagulant (most frequently detected in 82% of cases)
  • IgG anticardiolipin antibodies
  • Anti-β2-glycoprotein I antibodies
• Triple positivity (all three antibodies) indicates highest risk for thrombotic events

Treatment Algorithm Based on Clinical Presentation

1. Thrombotic APS Management

• First venous thromboembolism (VTE):

  • Warfarin with target INR 2.0-3.0 indefinitely 3, 2
  • For patients with first episode of DVT/PE who have documented antiphospholipid antibodies, treatment for at least 12 months is recommended and indefinite therapy is suggested 3

• Arterial thrombosis or recurrent thrombotic events:

  • High-intensity warfarin with target INR >3.0 (range 3.0-4.0) 3, 4
  • Alternative: Moderate-intensity warfarin (INR 2.0-3.0) plus low-dose aspirin (≤100 mg/day) 2

• Catastrophic APS (multiple organ thrombosis with high mortality):

  • Combination therapy with glucocorticoids, anticoagulation, and plasma exchange 1
  • Consider rituximab or eculizumab in refractory cases 1

2. APS Nephropathy Management

• Long-term anticoagulation with warfarin 1
• Higher complete response rates observed with anticoagulation (59.5% vs. 30.8%) 1
• Direct oral anticoagulants (DOACs) are not recommended as they were inferior to warfarin in preventing thromboembolic events 1, 2

3. Obstetric APS Management

• Low-dose aspirin plus low molecular weight heparin during pregnancy 2, 4
• Hydroxychloroquine should be continued during pregnancy to reduce risk of complications 1
• Start low-dose aspirin before 16 weeks of gestation 1

4. Primary Thromboprophylaxis in Asymptomatic aPL Carriers

• Low-dose aspirin is the first option 2
• Especially indicated for those with:
  • Persistently positive aPL
  • History of obstetric APS
  • Coexistent systemic lupus erythematosus 4

Adjunctive Therapies

• Hydroxychloroquine: Consider adding in patients with:

  • Systemic lupus erythematosus
  • Refractory thrombotic events
  • High bleeding risk 2, 5

• Statins: May be useful in complex settings due to their anti-inflammatory and immunomodulatory effects 2

• Immunosuppression: For patients with underlying autoimmune disorders or refractory cases 5

Monitoring Anticoagulation

• Lupus anticoagulant can affect phospholipid-dependent coagulation tests, potentially giving spurious results 6
• For warfarin monitoring:
  • Use alternative rate-correction formulas (Fridericia, Hodges, or Sagie/Framingham) rather than standard Bazett formula for QTc assessment 1
  • Maintain serum potassium above 4.0 mEq/L and magnesium above 1.8 mg/dL when using anticoagulation 1

Special Considerations

• Discontinuation of therapy: May be considered only in select low-risk primary APS patients whose aPL become persistently negative over time 7

• Renal impairment: Requires careful anticoagulant dosing and monitoring, particularly in APS nephropathy or catastrophic APS 6

• Thrombocytopenia: Requires individualized anticoagulation approach with careful monitoring 6

Common Pitfalls to Avoid

1. Using DOACs in triple-positive aPL patients or those with arterial thrombosis (warfarin is superior) 1, 2

2. Performing invasive procedures (central venous catheterization, lumbar puncture, bronchoscopy) during active coagulopathy 1

3. Discontinuing anticoagulation prematurely (treatment is typically lifelong for thrombotic APS) 3, 2

4. Failing to address additional cardiovascular risk factors (hypertension, hyperlipidemia, smoking) 2, 4

5. Inadequate monitoring of anticoagulation intensity, especially in patients with lupus anticoagulant which can affect test results 6