Cyclophosphamide Dosing in Antiphospholipid Syndrome
Cyclophosphamide is NOT a standard treatment for antiphospholipid syndrome (APLS) and should only be used in catastrophic APLS (CAPS) associated with systemic lupus erythematosus (SLE), at which point standard immunosuppressive dosing of 500-1000 mg IV monthly pulses or 1-3 mg/kg/day oral is appropriate. 1, 2
When Cyclophosphamide is Indicated in APLS
Cyclophosphamide has an extremely limited role in APLS management:
- Catastrophic APLS with concurrent SLE flare: This is the primary indication where cyclophosphamide is recommended as part of the treatment regimen 1, 2
- Refractory CAPS cases: When standard therapies (anticoagulation, corticosteroids, plasma exchange, IVIG) have failed 2
- Cyclophosphamide is NOT indicated for routine thrombotic APLS or obstetric APLS 3, 4, 5
Dosing Regimens When Indicated
When cyclophosphamide is used for CAPS with SLE:
- IV pulse therapy: 500-1000 mg IV monthly (approximately 15 mg/kg, maximum 1500 mg) 6
- Oral daily therapy: 1-3 mg/kg/day (maximum 200 mg/day) 6
- Duration should be limited to 3-6 months for remission induction 6
- Mesna protection is mandatory with IV pulse dosing to prevent hemorrhagic cystitis 6
Standard APLS Treatment (NOT Cyclophosphamide)
The cornerstone of APLS management does not involve cyclophosphamide:
- Thrombotic APLS: Warfarin with target INR 2.0-3.0 is first-line therapy 3, 4
- Obstetric APLS: Low molecular weight heparin plus low-dose aspirin throughout pregnancy 3, 4
- Catastrophic APLS without SLE: Anticoagulation (IV heparin), high-dose corticosteroids, plasma exchange, and/or IVIG 1, 2
Critical Pitfalls to Avoid
- Do not use cyclophosphamide for routine thrombotic APLS: The standard treatment is anticoagulation alone, not immunosuppression 3, 5
- Do not confuse APLS with ANCA-associated vasculitis: Cyclophosphamide is standard for vasculitis but not for APLS 7
- Recognize CAPS early: This life-threatening variant (affecting <1% of APLS patients) requires aggressive multimodal therapy including cyclophosphamide only when SLE is present 1, 2
- Monitor for gonadal toxicity: Amenorrhea occurs in 20-85% of menstruating women; counsel patients about fertility preservation before starting cyclophosphamide 6
- Provide PCP prophylaxis: Trimethoprim/sulfamethoxazole is required for all patients receiving cyclophosphamide 6
Refractory APLS Management
For anticoagulant-refractory thrombotic APLS (recurrent thrombosis despite adequate anticoagulation):
- Increase warfarin intensity to target INR 3.0-4.0 8
- Add antiplatelet therapy (aspirin or clopidogrel) to anticoagulation 4, 8
- Add hydroxychloroquine 200-400 mg daily, especially if underlying SLE 4, 8
- Consider rituximab or eculizumab for truly refractory cases 2, 8
- Cyclophosphamide is not recommended for refractory thrombotic APLS unless CAPS develops with SLE 2, 8