Antiphospholipid Syndrome (Detailed)

Antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilia characterized by persistent antiphospholipid antibodies that bind phospholipid-binding plasma proteins (primarily beta-2 glycoprotein I) on cell surfaces, activating endothelial cells, platelets, monocytes, and complement to produce a hypercoagulable state. APS may be primary (without underlying connective tissue disease) or secondary (associated with systemic lupus erythematosus or other autoimmune diseases). Estimated prevalence is 50 per 100,000 with female predominance (3:1 to 5:1) and peak age 30-50 years.

Diagnosis requires fulfilling at least one clinical and one laboratory criterion (Sapporo/Sydney 2006). Clinical criteria: vascular thrombosis (one or more episodes of arterial, venous, or small vessel thrombosis confirmed by imaging) OR pregnancy morbidity (>=1 unexplained death of morphologically normal fetus at >=10 weeks; >=1 premature birth at <34 weeks due to severe preeclampsia or placental insufficiency; >=3 unexplained consecutive spontaneous abortions at <10 weeks). Laboratory criteria require persistent positivity (>=12 weeks apart) of: lupus anticoagulant (clotting-based assays), anticardiolipin antibodies IgG/IgM (>40 GPL/MPL or >99th percentile), or anti-beta-2 glycoprotein I antibodies IgG/IgM (>99th percentile). Triple-positive patients (LA + aCL + anti-beta2GPI) have highest thrombotic risk.

Treatment depends on clinical manifestations: secondary prevention after thrombosis uses long-term warfarin with target INR 2.0-3.0 for venous thrombosis or first arterial event, INR 3.0-4.0 for recurrent thrombosis or arterial events. Direct oral anticoagulants (rivaroxaban, apixaban, dabigatran, edoxaban) are NOT recommended in triple-positive APS due to TRAPS and RAPS trials showing higher recurrence rates compared to warfarin. Pregnancy management requires prophylactic low-molecular-weight heparin (40 mg enoxaparin daily) plus low-dose aspirin (81 mg daily) starting before conception or early pregnancy through 6 weeks postpartum. Catastrophic APS (CAPS) is a rare (<1%) life-threatening syndrome with multiple simultaneous thromboses in three or more organs developing within one week, treated with combination therapy: therapeutic anticoagulation, high-dose glucocorticoids, plasma exchange, intravenous immunoglobulin, and rituximab or eculizumab in refractory cases. Mortality of CAPS is 30-50% even with treatment.