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Q1: Definition and classification (2 min)
Define antiphospholipid syndrome. Name the antibodies. How does primary differ from secondary APS, and how does APS differ from inherited thrombophilia? Model answer: APS (Hughes syndrome) is an acquired autoimmune thrombophilia defined by persistent antiphospholipid antibodies causing venous and/or arterial thrombosis and pregnancy morbidity. The antibodies are lupus anticoagulant, anticardiolipin (IgG/IgM) and anti-beta-2-glycoprotein-I. Primary APS has no underlying autoimmune disease; secondary APS is most often associated with SLE. Unlike inherited thrombophilia (factor V Leiden, antithrombin, protein C/S - predominantly venous thrombosis, no antibodies), APS causes BOTH arterial and venous thrombosis plus recurrent pregnancy loss.
Q2: Pathophysiology (3 min)
Explain how antiphospholipid antibodies cause thrombosis and pregnancy loss, and explain the lupus anticoagulant paradox. Model answer: The antibodies target phospholipid-binding proteins (mainly beta-2-glycoprotein-I and prothrombin) on endothelium, platelets and monocytes. Binding activates these cells (tissue-factor expression, platelet aggregation), activates complement and drives the coagulation cascade - a systemic prothrombotic state causing thrombosis in any vessel. In the placenta, microvascular thrombosis and complement-mediated trophoblast injury cause recurrent miscarriage, late fetal loss and pre-eclampsia. The lupus anticoagulant paradox: the antibody interferes with phospholipid-dependent tests in vitro, prolonging the APTT/dRVVT that does not correct on mixing (but corrects with excess phospholipid), yet is prothrombotic in vivo.
Q3: Diagnosis and investigations (2 min)
What are the classification criteria, and how do you confirm APS in the lab? Model answer: Revised Sapporo criteria: ONE clinical criterion (thrombosis of any vessel, OR pregnancy morbidity - three-plus miscarriages under 10 weeks, one fetal death over 10 weeks, or severe pre-eclampsia/placental insufficiency under 34 weeks) plus ONE lab criterion (lupus anticoagulant, medium-high-titre anticardiolipin IgG/IgM, or anti-beta-2-GPI). The antibody must be persistent, present on two occasions at least 12 weeks apart. A prolonged APTT not correcting on mixing but correcting with excess phospholipid suggests lupus anticoagulant; confirm with dRVVT. Screen for SLE (ANA, anti-dsDNA) and exclude other thrombophilias and malignancy.
Q4: Management (2 min)
How do you treat thrombotic APS, obstetric APS and catastrophic APS? Model answer: Thrombotic APS: lifelong anticoagulation - heparin/LMWH then warfarin (INR 2 to 3 venous; sometimes 3 to 4 or added aspirin for arterial). Avoid DOACs in high-risk/triple-positive APS (TRAPS trial). Add hydroxychloroquine, especially in SLE. Obstetric APS: stop warfarin (teratogenic), give low-dose aspirin plus prophylactic or treatment-dose LMWH throughout pregnancy and 6 weeks postpartum (DOACs also avoided). Catastrophic APS: combined therapy - anticoagulation plus high-dose corticosteroids plus plasma exchange plus IVIG; treat triggers (infection, surgery); critical care; consider eculizumab or rituximab if refractory.
Q5: Exam pearl (1 min)
Give the one-line association an examiner wants to hear for a young stroke, a prolonged APTT, and a recurrent miscarriage. Model answer: Young stroke, prolonged APTT that does not correct on mixing, and recurrent miscarriage - all point to antiphospholipid syndrome. Treat thrombosis with lifelong warfarin (avoid DOACs in high-risk APS), and pregnancy with aspirin plus LMWH.