Antiphospholipid Syndrome
An autoimmune disease that makes blood clot too easily, leading to deep vein thromboses, strokes, and recurrent miscarriages.
Emergency Management: Catastrophic APS requires immediate triple therapy: IV Heparin, high-dose IV corticosteroids, and IVIG or Plasmapheresis.
An autoimmune, hypercoagulable state caused by autoantibodies directed against phospholipid-binding proteins. It is characterized by recurrent venous or arterial thrombosis and/or adverse pregnancy outcomes.
Detailed Overview
Patients with APS have a dramatically increased risk of developing blood clots anywhere in the body, most commonly DVTs, PEs, and strokes. In pregnancy, the antibodies cause placental thrombosis and infarction, leading to recurrent miscarriages or stillbirths. It can occur on its own (primary) or with Lupus (secondary).
Epidemiology & Demographics
Estimated prevalence of 40-50 per 100,000. Much more common in females (approx. 5:1). Accounts for up to 15% of all recurrent miscarriages.
Etiological Mechanism
Autoantibodies against beta-2-glycoprotein I (B2GPI) and other phospholipid-protein complexes.
Primary Causes
Idiopathic, though often triggered by infections or drugs in genetically susceptible individuals.
Antiphospholipid antibodies (aPL), specifically anti-B2GPI, bind to cell-surface proteins on endothelial cells, monocytes, and platelets. This binding activates these cells, upregulating Tissue Factor expression, increasing thromboxane A2, and inhibiting natural anticoagulants (like Protein C). This creates a massive prothrombotic environment. In the placenta, aPL impairs trophoblast invasion and causes spiral artery thrombosis.
Diagnostic Criteria & Guidelines
Sapporo/Sydney Criteria: Requires at least 1 clinical event (vascular thrombosis OR pregnancy morbidity) AND at least 1 laboratory criteria (Lupus Anticoagulant, Anti-Cardiolipin IgG/IgM >40 units, or Anti-B2GPI IgG/IgM >99th percentile) present on two occasions at least 12 weeks apart.
For thrombotic APS: Lifelong anticoagulation with Warfarin (Target INR 2.0-3.0 for venous clots; Target INR 3.0-4.0 for arterial clots). Direct Oral Anticoagulants (DOACs like Rivaroxaban) are CONTRAINDICATED in triple-positive APS due to increased risk of arterial thrombosis. For obstetric APS (no prior clots): Low-dose Aspirin (81 mg) + Prophylactic Low-Molecular-Weight Heparin (LMWH, e.g., Enoxaparin 40 mg daily) during pregnancy and 6 weeks postpartum.
Second-Line & Adjunctive Therapy
For refractory thrombosis despite therapeutic Warfarin: Add Aspirin 81 mg, switch to therapeutic LMWH, or increase target INR. Hydroxychloroquine 200-400 mg daily if secondary to SLE.
Surgical & Procedural Management
Thrombectomy or inferior vena cava (IVC) filter in catastrophic cases or when anticoagulation is strictly contraindicated.
Patient Counseling & Advice
Counsel that Warfarin requires frequent blood draws and dietary consistency with Vitamin K. Warn women of childbearing age that pregnancies must be planned to switch from Warfarin (teratogenic) to Heparin before conception.
Follow-Up & Monitoring Schedule
Routine INR checks (every 2-4 weeks) for patients on Warfarin. High-risk maternal-fetal medicine monitoring during pregnancy with frequent fetal growth ultrasounds.
Preventive Strategies
Primary prophylaxis (Aspirin 81 mg) in aPL carriers is debated but often used in high-risk (triple-positive) profiles.
With compliant lifelong anticoagulation, the risk of recurrent clots is minimized, and pregnancy success rates exceed 70-80%. Non-compliance is deadly.