A 32-year-old woman presents with a 2-year history of recurrent spontaneous abortions and thrombotic episodes. Investigations reveal prolonged aPTT that does not correct on mixing study. Anticardiolipin antibodies and lupus anticoagulant are positive. What is the most common thrombotic complication in antiphospholipid syndrome?

## Most Common Thrombotic Site in Antiphospholipid Syndrome **Key Point:** Deep vein thrombosis (DVT) of the lower limbs is the most common thrombotic manifestation of antiphospholipid syndrome (APS), occurring in approximately 30–40% of patients with thrombotic APS. ### Epidemiology of Thrombotic Manifestations in APS | Thrombotic Site | Frequency | Notes | | --- | --- | --- | | DVT (lower limbs) | 30–40% | Most common venous thrombosis | | Pulmonary embolism | 5–10% | Often secondary to DVT | | Arterial thrombosis (cerebral) | 10–15% | More common than PE but less than DVT | | Mesenteric thrombosis | <5% | Rare, usually in severe cases | | Portal vein thrombosis | <5% | Rare, associated with cirrhosis | **High-Yield:** Venous thrombosis (especially DVT) is more common than arterial thrombosis in APS, contrary to what might be expected from the thrombophilic nature of the condition. ### Mechanism of Thrombosis in APS 1. Antiphospholipid antibodies (anticardiolipin, anti-β~2~-glycoprotein I, lupus anticoagulant) bind to phospholipid-binding proteins on endothelial cells and platelets 2. Activation of tissue factor pathway and complement cascade 3. Platelet aggregation and microthrombi formation 4. Endothelial cell activation and increased expression of adhesion molecules **Clinical Pearl:** The paradoxical finding of prolonged aPTT in vitro (due to antibody interference with phospholipid-dependent coagulation tests) contrasts sharply with the *in vivo* hypercoagulable state, making APS a "paradoxical" anticoagulant. **Mnemonic: APS Thrombotic Sites (VeAr)** — **Ve**nous (DVT most common) > **Ar**terial (cerebral second) ### Clinical Features Supporting DVT as Most Common - Lower limb DVT often recurrent and may be bilateral - Pulmonary embolism usually occurs as a consequence of DVT, not as primary thrombotic event - Arterial thrombosis (stroke, TIA) occurs but is less frequent than venous events - Rare sites (mesenteric, portal) are associated with severe, catastrophic APS **Warning:** Do not confuse APS with other hypercoagulable states (e.g., Factor V Leiden, prothrombin G20210A mutation) where arterial thrombosis may be more prominent in certain contexts. [cite:Robbins 10e Ch 4]