Coagulation and Transfusion Medicine Flashcards

During orthotopic liver transplantation, ROTEM analysis at the start of reperfusion reveals: EXTEM CT 840s (ref <80s), INTEM CT 620s (ref <240s), but HEPTEM CT 74s (ref <240s). EXTEM MCF and FIBTEM MCF are both within normal limits. What is the most appropriate immediate intervention?

Answer: Protamine sulfate 25–50 mg IV to reverse heparin effect from the donor liver flush

HEPTEM contains heparinase, which neutralises heparin in the sample. When HEPTEM CT normalises while EXTEM and INTEM CTs are markedly prolonged — with preserved MCF values — the pattern is pathognomonic for heparin effect rather than factor deficiency or fibrinolysis. This occurs because donor livers are flushed with heparin-containing preservation solution (e.g., University of Wisconsin solution) that releases into the circulation upon reperfusion. Small doses of protamine (25–50 mg) reverse this rapidly. FFP would not address a heparin effect, fibrinogen concentrate is irrelevant when MCF is normal, and TXA treats fibrinolysis (which would show an abnormal APTEM pattern).

A 72-year-old patient on rivaroxaban 20 mg once daily for non-valvular atrial fibrillation presents 4 hours after their last dose with a Glasgow Coma Scale of 8 and CT-confirmed large intracranial haematoma. Anti-Xa level is 195 ng/mL. Which andexanet alfa dosing regimen is correct?

Answer: High-dose: 800 mg IV bolus followed by 8 mg/min infusion for 120 minutes

Andexanet alfa dosing is stratified by agent, dose, and time since last administration. For rivaroxaban: low-dose protocol applies when the dose was ≤10 mg OR the last dose was ≥8 hours prior; high-dose protocol applies when the dose was >10 mg AND the last dose was 10 mg threshold) just 4 hours ago (<8 h threshold), mandating the high-dose regimen (800 mg bolus + 8 mg/min × 120 min). The anti-Xa level of 195 ng/mL confirms significant residual drug activity. Andexanet alfa is licensed for both apixaban and rivaroxaban reversal.

A patient with known immune thrombocytopenic purpura (ITP) and a platelet count of 9 × 10⁹/L requires emergency laparotomy for bowel perforation within 2 hours. Which statement regarding platelet transfusion is most accurate?

Answer: Platelet transfusion will be largely ineffective due to rapid antibody-mediated destruction; IV immunoglobulin with or without corticosteroids is the preferred strategy

In ITP, circulating anti-platelet IgG autoantibodies (targeting GPIIb/IIIa or GPIb/IX) cause rapid reticuloendothelial destruction of transfused platelets, typically within minutes to 1–2 hours. Transfusion is therefore largely ineffective when given hours before surgery. IVIg (1 g/kg/day for 1–2 days) saturates Fc receptors and can raise platelet counts within 24–48 hours; high-dose corticosteroids offer a similar effect over 2–5 days. If surgery cannot be delayed and platelet transfusion is deemed necessary, it should be given as a large dose (2–3 adult doses) immediately at the time of skin incision — not hours beforehand. It is not absolutely contraindicated but should not be the sole strategy.

Seven hours after receiving 2 units of packed red blood cells, an ICU patient with known moderate left ventricular systolic dysfunction (EF 35%) develops acute dyspnoea, SpO₂ 80% on 15 L/min O₂ via non-rebreather mask, bilateral infiltrates on CXR, temperature 38.1°C, and blood pressure 158/96 mmHg. CVP is 19 mmHg and BNP is 940 pg/mL. Urine output over the last 2 hours is 15 mL total. Which diagnosis and primary management strategy is correct?

Answer: TACO — furosemide 40–80 mg IV and supplemental oxygen or non-invasive ventilation

The clinical picture strongly favours TACO (transfusion-associated circulatory overload) over TRALI. Key distinguishing features here are: hypertension (TRALI characteristically causes hypotension), markedly elevated CVP (18 mmHg), very high BNP (>500 pg/mL strongly favours cardiogenic oedema), oliguria, and pre-existing LV dysfunction — all reflecting hydrostatic oedema from volume overload. TRALI is a non-cardiogenic, immune-mediated reaction characterised by fever, hypotension, low CVP, and BNP typically <250 pg/mL. While fever is shared by both conditions and is a common distractor, the haemodynamic and biochemical profile here is cardiogenic. TACO treatment centres on diuresis and respiratory support; corticosteroids are not indicated.

A 75 kg patient undergoing cardiopulmonary bypass received an initial heparin bolus of 400 units/kg (30,000 units) and two additional boluses totalling 8,000 units over a 3-hour bypass run. Post-bypass ACT is 540 seconds. Which protamine dosing strategy is most physiologically rational and minimises the risk of excess protamine anticoagulation?

Answer: Protamine dose-response titration (e.g., Hepcon HMS or equivalent) to estimate residual heparin activity, typically yielding 200–260 mg

Heparin has a plasma half-life of 60–90 minutes. After 3 hours on bypass with supplemental boluses, a significant fraction of the initial dose has been cleared or metabolised. Calculating protamine based on the total cumulative dose (option A: 380 mg) substantially overestimates residual heparin and risks protamine excess. Excess protamine itself is anticoagulant (inhibits thrombin and platelet function), triggers pulmonary hypertension via complement activation, and causes platelet dysfunction — all catastrophic post-bypass. Point-of-care protamine dose-response titration (e.g., Hepcon HMS) measures the actual heparin concentration in the patient's blood and calculates the precise neutralising protamine dose, typically 200–260 mg in this scenario. This is the most physiologically sound strategy endorsed by STS/SCA guidelines.

A patient with acute fulminant hepatic failure (King's College criteria met, transplant pending) is receiving rapid massive transfusion at a rate of 1 unit of packed red blood cells every 10 minutes for variceal haemorrhage. Which parameter most reliably identifies clinically significant citrate toxicity in this context?

Answer: Ionised calcium (iCa²⁺) below 0.9 mmol/L accompanied by cardiovascular depression (hypotension, reduced cardiac contractility, or new arrhythmia)

Citrate, the anticoagulant preservative in blood products, chelates free ionised calcium. In healthy patients, the liver rapidly metabolises citrate; however, in acute liver failure, citrate clearance is severely impaired, leading to accumulation. Total serum calcium (option A) is unreliable because the majority is protein-bound and does not reflect bioavailable calcium — a patient may have a normal total calcium yet critical ionised hypocalcaemia. The iCa²⁺ is the physiologically active fraction; values below 0.9 mmol/L cause reduced myocardial contractility, vasodilation, prolonged QT, and coagulopathy. Cardiovascular signs (hypotension, low cardiac output on monitoring) signal clinically significant toxicity requiring calcium supplementation (calcium gluconate or chloride IV). QTc prolongation can occur but is a later and less sensitive sign. Rising PT reflects the underlying liver failure or dilutional coagulopathy, not citrate toxicity per se.