A 35-year-old woman presents with recurrent thrombosis and recurrent pregnancy losses. Investigations reveal prolonged aPTT that does not correct on mixing study. Which of the following is NOT a characteristic feature of Antiphospholipid Syndrome?

## Antiphospholipid Syndrome (APS): Diagnostic & Laboratory Features **Key Point:** The hallmark laboratory finding in APS is a prolonged aPTT that does NOT correct on mixing study — this is the critical diagnostic clue that distinguishes APS from factor deficiencies. ### Why aPTT Does NOT Correct in APS In APS, the prolonged aPTT is caused by **lupus anticoagulant (LA)**, an immunoglobulin that binds to phospholipid-protein complexes in vitro. When patient plasma is mixed with normal plasma: - The LA from the patient plasma continues to inhibit the phospholipid-dependent reactions in the normal plasma - The aPTT remains prolonged (non-correction) - This is pathognomonic for LA and APS In contrast, factor deficiencies (e.g., Factor VIII deficiency) will show **correction** on mixing because the normal plasma supplies the missing factor. ### Diagnostic Criteria for APS (Sydney 2006) | Criterion | Details | |-----------|----------| | **Clinical** | Thrombosis (arterial/venous) OR pregnancy morbidity (≥3 consecutive losses <10 weeks OR ≥1 unexplained fetal death ≥10 weeks) | | **Laboratory** | Lupus anticoagulant (LA) OR Anticardiolipin (aCL) IgG/IgM ≥40 GPL/MPL units OR Anti-β~2~-glycoprotein-I IgG/IgM ≥40 units | | **Timing** | Lab abnormality must be present on ≥2 occasions ≥12 weeks apart | **High-Yield:** The three characteristic lab tests for LA are: 1. **aPTT** — prolonged, non-correcting on mixing 2. **DRVVT** (Dilute Russell Viper Venom Time) — prolonged, corrects with phospholipid (confirmatory) 3. **Platelet Neutralization Procedure** — shortens aPTT (confirms LA) ### Clinical Pearl APS is a **paradoxical thrombophilia**: despite prolonged aPTT (which would suggest bleeding), patients have **increased thrombotic risk**. This is because the anticoagulant effect is in vitro only; in vivo, the antibodies promote thrombosis via: - Activation of endothelial cells - Platelet activation - Complement activation - Tissue factor upregulation ### Why Option 0 Is Incorrect The statement "Prolonged aPTT that **corrects** on mixing with normal plasma" is **NOT a feature of APS**. This is the key distinction. Correction on mixing indicates a factor deficiency, not LA. The presence of **non-correcting** prolonged aPTT is what makes APS unique and diagnostically important. ### Why Other Options Are Correct - **Option 1:** Lupus anticoagulant and anticardiolipin antibodies are the defining serological markers of APS. - **Option 2:** Thrombosis and pregnancy morbidity are the clinical manifestations required for diagnosis. - **Option 3:** DRVVT is a confirmatory test; it is prolonged in LA and corrects when phospholipid is added (phospholipid neutralization).