Antiphospholipid Syndrome — SAQ

Stem

A 31-year-old woman is admitted with a swollen, painful left leg. Doppler ultrasound confirms a proximal deep-vein thrombosis. She had an ischaemic stroke at 27 with full recovery, and has had three consecutive first-trimester miscarriages. She has a malar rash and photosensitivity. Her APTT is 48 seconds (reference 25 to 35) with a normal PT; it does not correct on a mixing study but corrects with excess phospholipid. Full blood count shows platelets 110 x 10^9/L.

Questions

a) What is the most likely diagnosis, and which two clinical criteria and the key laboratory finding support it? (2 marks) Diagnosis: secondary antiphospholipid syndrome (APS) associated with systemic lupus erythematosus (malar rash, photosensitivity, prior stroke and miscarriages). Clinical criteria: (1) thrombosis (proximal DVT now and prior ischaemic stroke - arterial and venous) and (2) pregnancy morbidity (three consecutive unexplained miscarriages under 10 weeks). Key laboratory finding: lupus anticoagulant - a prolonged APTT that does not correct on mixing but corrects with excess phospholipid. b) State the full laboratory criteria for definite APS and the timing requirement. (2 marks) One or more of: lupus anticoagulant present, anticardiolipin IgG/IgM at medium or high titre (over 40 GPL/MPL or above the 99th percentile), or anti-beta-2-glycoprotein-I IgG/IgM (above the 99th percentile). The antibody must be persistent, present on two or more occasions at least 12 weeks apart (revised Sapporo criteria). Diagnosis requires one clinical plus one lab criterion. c) Explain the lupus anticoagulant paradox. (3 marks) The lupus anticoagulant is an antibody (against phospholipid-binding proteins, mainly beta-2-glycoprotein-I) that interferes with phospholipid-dependent coagulation tests in vitro, producing a prolonged APTT (and dRVVT) that, because the inhibitor persists in the mixture, does not correct on a mixing study, yet does correct when excess phospholipid is added. Paradoxically, despite this laboratory anticoagulant effect, the antibody is prothrombotic in vivo: it activates endothelium, platelets, monocytes and complement, producing venous and arterial thrombosis. The practical danger is misreading the prolonged APTT as a bleeding tendency and withholding necessary anticoagulation. d) Outline the short-term and long-term management for this woman, including her next planned pregnancy. (3 marks) Acute DVT: therapeutic low-molecular-weight heparin, then transition to lifelong warfarin (target INR 2 to 3; consider 3 to 4 or added aspirin if arterial events recur). Avoid DOACs in high-risk APS (TRAPS trial showed excess thrombosis with rivaroxaban). Add hydroxychloroquine because of SLE. For a future pregnancy: stop warfarin (teratogenic, especially weeks 6 to 12) and switch to low-dose aspirin plus prophylactic or treatment-dose LMWH throughout pregnancy and for 6 weeks postpartum (DOACs also avoided). Plan delivery around neuraxial anaesthesia and anticoagulation timing, and arrange combined obstetric-haematology care.