Coagulation Disorders Viva

Long Case Viva Defence

Candidate's opening statement (model answer)

"Mrs Chen is a 58-year-old woman with a history of systemic lupus erythematosus who presents with a three-day history of progressive dyspnoea, pleuritic chest pain and left calf swelling. She has had two first-trimester miscarriages in the past. CT pulmonary angiogram confirms a segmental pulmonary embolism. Her coagulation screen shows a prolonged aPTT of 48 seconds that does not correct on mixing study, with a positive lupus anticoagulant, high-titre anticardiolipin IgG of 45 GPL, and positive anti-beta-2 glycoprotein I antibodies. Her platelet count is 95." ^[1]

"Her main problems are:

1. Antiphospholipid syndrome with acute pulmonary embolism and deep vein thrombosis — requiring emergency anticoagulation and lifelong warfarin
2. Secondary APS to SLE — the underlying autoimmune condition
3. Recurrent pregnancy morbidity from APS placental microthrombosis
4. Mild thrombocytopenia from platelet activation and consumption ^[1]

"My immediate priorities are to anticoagulate with low-molecular-weight heparin, bridge to warfarin with a target INR of 2 to 3, and plan lifelong anticoagulation." ^[1]

Examiner probing questions and model answers

Q1: "Explain why her aPTT is prolonged when she is thrombosing." ^[1]

"This is the hallmark paradox of the lupus anticoagulant. In the test tube, the lupus anticoagulant binds to the phospholipid in the aPTT reagent, interfering with the clotting reaction and prolonging the time — it acts as an anticoagulant in the laboratory. But in the body, the same antibodies — directed against beta-2 glycoprotein I and prothrombin — activate endothelial cells, monocytes and platelets, creating a prothrombotic state. The prolonged aPTT is a laboratory artefact; the clinical reality is thrombosis. This is why the mixing study is so important — it confirms that the prolonged aPTT is from an inhibitor, not a factor deficiency, and the confirmatory test — the dRVVT, which is phospholipid-dependent and corrects with excess phospholipid — confirms the lupus anticoagulant ^[2]."

Q2: "How do you diagnose antiphospholipid syndrome?" ^[1]

"APS is classified using the Sydney criteria from 2006, which require at least one clinical criterion and one laboratory criterion, confirmed on two occasions at least 12 weeks apart. The clinical criteria are vascular thrombosis — arterial, venous or small vessel — or pregnancy morbidity, which includes recurrent early miscarriage before 10 weeks, one fetal death after 10 weeks, or premature birth before 34 weeks due to pre-eclampsia or placental insufficiency. The laboratory criteria are a lupus anticoagulant, anticardiolipin antibodies at moderate-to-high titre — above 40 GPL or MPL — or anti-beta-2 glycoprotein I antibodies; any one, persistently positive, suffices. This patient has a pulmonary embolism and recurrent miscarriage, and she is triple-positive — meeting the laboratory criterion three times over, which carries the highest thrombotic risk ^[1]."

Q3: "Why warfarin and not a DOAC?" ^[1]

"Warfarin is preferred over direct oral anticoagulants in APS because the TRAPS trial — a randomised comparison of rivaroxaban versus warfarin in triple-positive APS patients with a history of thrombosis — showed a significantly higher rate of thrombotic events with rivaroxaban. The concern is that DOACs may not provide adequate anticoagulation in the highly prothrombotic milieu of APS, particularly in triple-positive patients — those positive for lupus anticoagulant, anticardiolipin and anti-beta-2 glycoprotein I — who are at the highest risk. So the standard of care for APS-related thrombosis remains warfarin. There may be selected patients in whom a DOAC is reasonable — for example, single-positive patients with a first venous event and a strong contraindication to warfarin — but this is not first-line ^[1]."

Q4: "How long will she need anticoagulation?" ^[1]

"Lifelong. APS-related thrombosis recurs at a very high rate when anticoagulation is stopped — in some studies, over 50 per cent recur within a year. This is one of the few conditions where anticoagulation is truly indefinite. I would explain to the patient that her blood has a persistent tendency to clot because of these antibodies, and that stopping the blood thinner puts her at high risk of another pulmonary embolism, a deep vein thrombosis, or even a stroke — because APS also causes arterial thrombosis. The only scenario in which I would consider stopping is if she developed a life-threatening bleeding complication that made anticoagulation impossible — and even then, I would explore all alternatives before stopping." ^[1]

Q5: "She wants to become pregnant. How does this change your management?" ^[1]

"Pregnancy requires a coordinated haematology-obstetric plan. Warfarin is teratogenic and must be stopped before conception — switched to low-molecular-weight heparin. The standard regimen for APS with prior thrombosis is low-dose aspirin plus treatment-dose LMWH throughout pregnancy and for six weeks postpartum, then switch back to warfarin. This regimen significantly reduces the risk of recurrent thrombosis and pregnancy loss. I would also ensure hydroxychloroquine is continued, as it reduces thrombotic risk and may improve pregnancy outcomes. Close monitoring by a high-risk obstetric service is essential — these pregnancies are at elevated risk of pre-eclampsia, intrauterine growth restriction and fetal loss ^[1]."

Q6: "What is catastrophic antiphospholipid syndrome and how would you recognise it?" ^[1]

"Catastrophic APS, or CAPS, is a rare but life-threatening variant affecting less than 1 per cent of APS patients. It presents as diffuse microvascular thrombosis causing multi-organ failure over days to weeks — renal failure, respiratory failure, cerebral dysfunction, skin necrosis in the form of purpura fulminans, and a DIC-like coagulopathy. The mortality is 30 to 50 per cent. It is often triggered by infection, surgery or pregnancy. If Mrs Chen were to develop rapidly progressive multi-organ failure with new thrombocytopenia and schistocytes, I would suspect CAPS and initiate triple therapy immediately — therapeutic heparin, high-dose corticosteroids and plasma exchange, with consideration of IVIG, cyclophosphamide if she has active SLE, and rituximab or eculizumab for refractory cases. The key is early recognition and aggressive multi-modal treatment ^[2]."