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. This patient meets all of these: she has a pulmonary embolism, recurrent miscarriage, and all three laboratory criteria are positive [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]."

Short Case Discussion

Scenario: "Interpret this coagulation screen"

Provided data: A 22-year-old man with recurrent haemarthrosis since childhood. Platelets 280 x 10^9/L, PT 12 seconds (normal), aPTT 72 seconds (prolonged). Mixing study: the aPTT corrects with normal pooled plasma. Factor VIII level: 0.02 IU/mL (2 per cent). [1]

Candidate presentation (model): [1]

"The platelet count is normal and the PT is normal, so the problem is isolated to the intrinsic pathway — the aPTT is markedly prolonged at 72 seconds. The mixing study corrects, which tells me this is a factor deficiency, not an inhibitor — the normal plasma supplies the missing factor. The factor VIII level is 2 per cent, which confirms severe haemophilia A. The severity classification is by factor level: less than 1 per cent is severe, 1 to 5 is moderate, and above 5 is mild. At 2 per cent, this is moderate haemophilia A — but the clinical history of recurrent spontaneous haemarthrosis suggests the level may have been lower previously, or the clinical phenotype is more severe than the number suggests. The recurrent haemarthrosis is the hallmark of haemophilia — deep tissue bleeding from a factor deficiency, as opposed to the mucocutaneous bleeding of a platelet or vWF problem." [1]

"My next steps are: first, to confirm there is no inhibitor — a Bethesda assay should be sent, because approximately 30 per cent of severe haemophilia A patients develop alloantibodies against factor VIII after exposure to factor replacement, and the inhibitor would change management. Second, to assess for joint damage from the recurrent haemarthrosis — a clinical examination and possibly imaging of the affected joints. Third, to discuss prophylaxis — for severe or recurrent-bleed haemophilia A, the modern standard of care is subcutaneous emicizumab, a bispecific antibody that bridges factor IXa and X, effectively replacing the function of factor VIII [4]."

Examiner: "What is the difference between haemophilia A and haemophilia B?" [1]

"They are clinically indistinguishable — both are X-linked recessive, both cause haemarthrosis and deep tissue bleeding, both produce an isolated prolonged aPTT with a normal PT that corrects on the mixing study, and both are classified by factor level. The only way to tell them apart is the factor assay: haemophilia A is factor VIII deficiency and haemophilia B is factor IX deficiency. The treatment differs because the factors differ — haemophilia A is treated with recombinant factor VIII or emicizumab, and haemophilia B is treated with recombinant factor IX. Haemophilia A is about five times more common. DDAVP is effective in mild haemophilia A — it releases stored factor VIII — but not in haemophilia B, because factor IX is not stored in endothelial Weibel-Palade bodies." [1]

Examiner: "A woman with lifelong heavy periods, epistaxis and dental bleeding has a normal PT, a slightly prolonged aPTT, and a vWF antigen of 0.3 IU/mL. What is she likely to have, and what is the first-line treatment?" [1]

"This is type 1 von Willebrand disease — the most common inherited bleeding disorder. The mucocutaneous bleeding pattern (heavy periods, epistaxis, dental bleeding) is typical of a primary haemostasis problem — vWF mediates platelet adhesion. The slightly prolonged aPTT is from a secondary factor VIII reduction, because vWF is the carrier protein for factor VIII and when vWF is low, factor VIII is cleared faster. The vWF antigen of 0.3 confirms partial quantitative deficiency — the activity-to-antigen ratio would be preserved in type 1 (proportionate reduction), distinguishing it from type 2 where the ratio is low (dysfunctional vWF). The first-line treatment is DDAVP — desmopressin — which stimulates the release of stored vWF and factor VIII from endothelial Weibel-Palade bodies, approximately doubling their plasma levels. A DDAVP trial should be performed before surgery to confirm responsiveness. The one subtype where DDAVP is dangerous is type 2B — the abnormal vWF has enhanced platelet binding, and DDAVP causes worsening thrombocytopenia by releasing this dysfunctional vWF." [1]

Examiner: "Walk me through a DIC lab pattern." [1]

"DIC produces a consumption coagulopathy with simultaneous microvascular thrombosis. The lab pattern is: low platelets — from consumption; prolonged PT and aPTT — from consumption of factors V, VII, X and II; low fibrinogen — from consumption and plasmin degradation; markedly elevated D-dimer — from fibrinolysis of cross-linked fibrin; and schistocytes on the blood film — from microangiopathic haemolysis as red cells are sheared against intravascular fibrin strands. The ISTH DIC score integrates platelets, D-dimer, PT prolongation and fibrinogen into a composite score; a score of 5 or more in a patient with an underlying trigger is compatible with overt DIC [3]."

"The critical point about management is that DIC is a syndrome, not a disease — the first step is always to find and treat the underlying cause. Sepsis is the most common trigger, followed by obstetric catastrophe, malignancy — especially acute promyelocytic leukaemia — and massive trauma. Blood products — FFP, cryoprecipitate and platelets — support the patient while the trigger is addressed, but they are consumed as fast as they are given if the cause is not treated." [1]

Examiner: "What is the single most common error candidates make in the coagulation viva?" [1]

"Assuming that a prolonged clotting time means a bleeding tendency. The candidate sees a prolonged aPTT and immediately thinks 'haemophilia — bleeding risk' without performing or interpreting the mixing study. But the prolonged aPTT from a lupus anticoagulant does not correct on mixing and predicts thrombosis, not bleeding. The disciplined approach is: see the prolonged clotting time, ask whether the patient is bleeding or thrombosing, do the mixing study, and only then commit to a diagnosis. The mixing study is the gateway to the abnormal coagulation screen." [1]