Coagulation and Transfusion Medicine Flashcards

A 58-year-old patient on warfarin (INR 3.8) requires emergency neurosurgery after intracranial hemorrhage. 4-factor PCC is administered. Which statement best describes the mechanism by which 4F-PCC achieves more rapid INR reversal than Fresh Frozen Plasma?

Answer: 4F-PCC delivers concentrated vitamin K-dependent factors (II, VII, IX, X) plus Proteins C and S at 25-fold higher concentration per volume than FFP

4-factor PCC (Beriplex, Octaplex) contains factors II, VII, IX, X plus the natural anticoagulants Proteins C and S, delivered at approximately 25-fold the concentration found in FFP. This allows full INR reversal with volumes as small as 25–50 mL rather than 15–30 mL/kg of FFP, avoiding volume overload. It does not contain activated factors (unlike aPCC/FEIBA), does not interact with VKORC1 directly, and does not contain rFVIIa.

During massive transfusion for trauma, viscoelastic testing (ROTEM) shows: EXTEM CT 95s (normal 50mm), FIBTEM MCF 6mm (normal >10mm), INTEM CT 260s (normal <240s). Which targeted intervention is MOST appropriate as the first priority?

Answer: Administer fibrinogen concentrate or cryoprecipitate to correct FIBTEM MCF

FIBTEM MCF reflects fibrinogen-dependent clot strength (platelet contribution is blocked by cytochalasin D). An FIBTEM MCF of 6mm indicates severe hypofibrinogenaemia as the primary driver. In ROTEM-guided therapy, low FIBTEM MCF is corrected first with fibrinogen concentrate (target FIBTEM MCF >10mm) before addressing platelet or factor deficits, because fibrinogen is the first coagulation factor to fall critically low during massive haemorrhage. The low EXTEM MCF in this case is predominantly fibrinogen-driven, not platelet-driven. The moderately prolonged CTs are secondary priorities.

A patient with Type 2B von Willebrand Disease requires major elective surgery. Which therapeutic approach is CONTRAINDICATED and why?

Answer: DDAVP (desmopressin), because it causes release of abnormal VWF that binds and aggregates platelets, potentially worsening thrombocytopenia

Type 2B VWD is caused by a gain-of-function mutation in the A1 domain of VWF that causes spontaneous binding to platelet GpIbα even without shear stress. Administering DDAVP releases large stores of this abnormal VWF from Weibel-Palade bodies, resulting in spontaneous platelet aggregation and potentially severe thrombocytopenia. DDAVP is therefore specifically contraindicated in Type 2B VWD. Treatment requires VWF concentrate (which replaces normal VWF) and platelet transfusion if thrombocytopenic. Tranexamic acid and rFVIIa are not contraindicated.

A patient with heparin-induced thrombocytopenia (HIT) confirmed by positive PF4-heparin ELISA and positive serotonin release assay requires urgent coronary artery bypass grafting. Which anticoagulation strategy is the preferred choice for cardiopulmonary bypass?

Answer: Bivalirudin with monitoring by ACT targets adjusted to >480 seconds

Bivalirudin is the preferred anticoagulant for cardiac surgery with CPB in confirmed HIT. Unlike argatroban, bivalirudin is cleared primarily by enzymatic degradation (not hepatically), has predictable pharmacokinetics during CPB, and can be monitored with ACT (target >480s during CPB, higher than standard heparin targets). Argatroban is hepatically cleared and accumulates unpredictably during the hypothermic, non-pulsatile flow of CPB, making it a less reliable choice. Fondaparinux has no reversal agent and its behaviour on CPB is inadequately characterised. Unfractionated heparin is absolutely contraindicated in acute HIT as all heparin formulations (including LMWH) cross-react with HIT antibodies.

In a trauma patient receiving massive transfusion, rotational thromboelastometry (ROTEM) demonstrates an isolated, markedly prolonged EXTEM lysis index at 30 minutes (LI30 <85%) with a normal FIBTEM and INTEM. What does this pattern indicate and what is the most appropriate intervention?

Answer: Hyperfibrinolysis as the dominant abnormality — treat with tranexamic acid

An LI30 <85% on EXTEM (or LI60 <85%) indicates fibrinolysis occurring within 30 minutes of clot formation, a hallmark of hyperfibrinolysis. This pattern is distinct from DIC (which shows prolonged CTs and low MCF) and Factor XIII deficiency (which prolongs clot retraction but not early lysis). Hyperfibrinolysis in trauma is driven by massive tissue plasminogen activator release from endothelium. The CRASH-2 and MATTERS trials demonstrated mortality benefit of tranexamic acid (TXA) in trauma haemorrhage, and ROTEM-guided TXA use is standard practice. TXA is most effective when given within 3 hours of injury. Isolated hyperfibrinolysis does not require FFP or platelets.

A 45-year-old patient with cirrhosis (Child-Pugh C) has an INR of 2.9 prior to an invasive hepatic procedure. The anesthesiologist debates whether to correct the INR. Which statement most accurately reflects the haemostatic balance in decompensated cirrhosis?

Answer: Cirrhotic patients have a rebalanced haemostasis with proportional reduction in both pro- and anticoagulant factors; the elevated INR overestimates bleeding risk because it does not capture concurrent reductions in Protein C and S

The concept of 'rebalanced haemostasis' in cirrhosis (Tripodi et al., NEJM 2011) is fundamental. Cirrhosis reduces both procoagulant factors (II, V, VII, IX, X) AND anticoagulant proteins (Protein C, Protein S, antithrombin). The PT/INR only measures procoagulant factor activity (calibrated against vitamin K deficiency, not liver disease) and therefore dramatically overestimates bleeding risk. Thrombin generation assays in cirrhotic plasma show near-normal or even hypercoagulable states when Protein C is added. Similarly, VWF levels rise in cirrhosis (from impaired clearance), partially compensating for thrombocytopenia. Routine FFP correction of INR in cirrhosis before procedures is not evidence-based and risks volume overload and citrate toxicity.