A 38-year-old woman presents with recurrent deep vein thrombosis (DVT) of the lower limbs despite 6 months of anticoagulation therapy. She has no family history of thrombophilia and her recent imaging shows a new thrombosis in the contralateral leg. Which investigation is most appropriate to establish the underlying prothrombotic state?

Explanation

## Investigation of Antiphospholipid Syndrome (APS) **Key Point:** Recurrent thrombosis despite adequate anticoagulation is a hallmark presentation of antiphospholipid syndrome (APS). The diagnostic triad includes clinical thrombosis (venous or arterial) plus laboratory evidence of antiphospholipid antibodies. **High-Yield:** The three antibodies that define APS are: 1. Lupus anticoagulant (LA) 2. Anticardiolipin antibodies (aCL) — IgG and/or IgM 3. Anti-β2-glycoprotein-I antibodies (anti-β2-GPI) — IgG and/or IgM At least one must be present on two occasions ≥12 weeks apart for diagnosis [cite:Harrison 21e Ch 139]. ### Why This Presentation Screams APS | Feature | Significance | | --- | --- | | **Recurrent thrombosis** | Suggests thrombophilia rather than single provoked event | | **Despite anticoagulation** | Implies intrinsic prothrombotic state (not just inadequate dosing) | | **Bilateral involvement** | Pattern consistent with systemic hypercoagulability | | **No family history** | Argues against inherited thrombophilia (Factor V Leiden, prothrombin mutation) | **Clinical Pearl:** APS is the most common acquired thrombophilia. It is responsible for 5–15% of unprovoked VTE cases and should be suspected in any patient with recurrent thrombosis despite adequate anticoagulation. **Tip:** Testing must be done ≥12 weeks after the acute thrombotic event to avoid false negatives (antibodies may be transiently low during acute phase). ## Why Other Tests Are Suboptimal - **PT/aPTT:** Screening coagulation tests; aPTT may be prolonged in LA-positive patients, but this is not diagnostic and does not identify the specific antibodies. - **Protein C/S during acute thrombosis:** Vitamin K-dependent factors are consumed during thrombosis and are not reliable for diagnosis in the acute phase; also, deficiency is rare and inherited. - **D-dimer and FDP:** Markers of ongoing fibrinolysis; nonspecific and do not identify the cause of recurrent thrombosis.