Coagulation and Transfusion Medicine Flashcards

A 58-year-old patient on warfarin (INR 3.8) requires emergency reversal before urgent neurosurgery. You administer 4-factor PCC (50 IU/kg). Thirty minutes later the INR is still 2.1. Which statement best explains this residual coagulopathy and guides your next step?

Answer: Warfarin also inhibits vitamin K–dependent carboxylation of factors in the endoplasmic reticulum; until hepatic re-synthesis is complete the functional factor activity will lag behind the measured INR, and a single dose of IV vitamin K 10 mg is the appropriate adjunct

PCC rapidly replenishes the vitamin K–dependent clotting factors (II, VII, IX, X, protein C and S), but these are the carboxylated forms stored in the vial. Warfarin blocks hepatic γ-carboxylation, so newly synthesised factors remain non-functional until vitamin K is restored. IV vitamin K (5–10 mg) enables resumed carboxylation within 6–12 hours and is a mandatory adjunct to PCC for complete and durable reversal. A second PCC dose risks thromboembolism and is rarely indicated; rFVIIa is not first-line here; and heparin contamination is not a clinically meaningful source of INR elevation with modern PCCs.

During massive transfusion for a ruptured abdominal aortic aneurysm, rotational thromboelastometry (ROTEM) shows: EXTEM CT normal, EXTEM CFR severely prolonged (>140 sec), EXTEM MCF 25 mm, FIBTEM MCF 4 mm. Which targeted intervention is most appropriate?

Answer: Administer cryoprecipitate or fibrinogen concentrate, as the pattern indicates isolated hypofibrinogenaemia

In ROTEM interpretation, EXTEM MCF reflects contributions from fibrinogen and platelets, while FIBTEM MCF isolates fibrinogen's contribution (platelet contribution is blocked by cytochalasin D). A low EXTEM MCF (25 mm) combined with a low FIBTEM MCF (4 mm, normal >10 mm) indicates the primary deficit is fibrinogen — not platelets, because if platelets were the problem, FIBTEM MCF would be preserved. The prolonged CFR (clot formation rate, equivalent to α-angle) reinforces poor fibrin polymerisation. FFP provides inadequate fibrinogen concentrations (~2 g/L) to correct severe hypofibrinogenaemia rapidly. The correct action is fibrinogen concentrate or cryoprecipitate. Platelet concentrate would be indicated if EXTEM MCF were low with normal FIBTEM MCF.

A patient with type 2B von Willebrand disease (vWD) requires elective hip arthroplasty. DDAVP (desmopressin) is considered for perioperative haemostasis. Why is DDAVP contraindicated in type 2B vWD?

Answer: DDAVP stimulates release of ultra-large vWF multimers from Weibel–Palade bodies; in type 2B the mutant vWF has enhanced affinity for platelet GPIb, causing platelet agglutination, consumptive thrombocytopenia, and paradoxical worsening of bleeding

Type 2B vWD is caused by gain-of-function mutations in the vWF A1 domain that increase its spontaneous binding affinity for platelet GPIbα, even under low-shear conditions. DDAVP stimulates endothelial release of stored ultra-large vWF multimers from Weibel–Palade bodies. Releasing more of this hyperreactive vWF causes massive platelet agglutination in vivo, leading to thrombocytopenia and paradoxically worsening haemostasis. Treatment for type 2B vWD includes vWF concentrates (without DDAVP) and, if thrombocytopenic, platelet transfusion. Type 2B patients do have vWF but it is dysfunctional.

A 34-year-old woman on direct oral anticoagulants (DOAC) — specifically dabigatran — presents with life-threatening intracranial haemorrhage. Idarucizumab is not immediately available. Which alternative haemostatic strategy has the strongest evidence in this scenario?

Answer: Activated charcoal to reduce further gastrointestinal absorption of dabigatran, combined with haemodialysis given dabigatran's low protein binding and renal clearance

Dabigatran is unique among DOACs in having low plasma protein binding (~35%) and predominantly renal elimination (80%). This pharmacokinetic profile makes haemodialysis a genuinely effective reversal strategy — it removes approximately 60% of dabigatran within 2–3 hours. Activated charcoal is useful within 1–2 hours of ingestion to limit further absorption. FFP has no direct reversal effect on direct thrombin inhibitors and is not recommended. 4-factor PCC has weaker evidence for dabigatran compared to factor Xa inhibitors; it does not directly neutralise thrombin inhibition and carries thrombotic risk. rFVIIa similarly does not reverse dabigatran and carries high thrombotic risk. When idarucizumab is unavailable, dialysis is the most evidence-supported alternative for dabigatran specifically.

A group O Rh-negative female patient (age 28) undergoes emergency trauma laparotomy receiving 6 units of uncrossmatched group O Rh-negative packed red cells. After haemorrhage control, serology shows she has anti-K (Kell) antibodies from a prior pregnancy. Which statement most accurately describes the haemolytic risk from this transfusion?

Answer: Anti-K antibodies can cause severe delayed haemolytic transfusion reactions if any of the transfused units were Kell-antigen positive; the incidence of K-positivity in random donors is ~9%, making this a real risk that requires serological follow-up

Anti-K (anti-Kell, anti-K1) is one of the most clinically significant non-ABO alloantibodies. It can cause severe acute and delayed haemolytic transfusion reactions. Approximately 9% of random blood donors are K-antigen positive, so if any of the 6 units transfused happened to be K-positive, a potentially severe haemolytic reaction — acute or delayed (days 3–10) — could occur. Uncrossmatched 'universal donor' blood is only universal for ABO/Rh compatibility; minor antigen mismatches (Kell, Kidd, Duffy, etc.) are not screened. This patient needs close haematological monitoring, and future transfusions must be Kell-antigen negative. Anti-K absolutely causes adult haemolytic transfusion reactions — this is a core transfusion medicine fact.

In the context of dilutional coagulopathy during massive transfusion, which statement correctly describes the relationship between prothrombin time (PT) prolongation and actual surgical bleeding risk?

Answer: The PT measures only the extrinsic/common pathway under optimised in-vitro conditions at 37°C with excess tissue factor; it poorly reflects in-vivo thrombin generation capacity, and significant coagulopathy can exist with a PT 1.5× normal do not bleed microvascularly

The PT (and INR) is performed in plasma at 37°C with supraphysiological concentrations of tissue factor, calcium, and phospholipid added — conditions that maximise clotting efficiency far beyond what occurs in vivo. Studies consistently show poor correlation between PT <1.5× normal and actual microvascular bleeding, and many patients with modestly elevated PT do not bleed. Conversely, viscoelastic testing (ROTEM/TEG) is more predictive of surgical coagulopathy. The TRICC and other trials demonstrate that PT-guided transfusion triggers lead to over-transfusion of FFP. While factor VII has the shortest half-life (~4–6 hours), PT prolongation in dilutional coagulopathy reflects global factor dilution, not selective factor VII deficiency. Citrate in RBC units is rapidly metabolised by the liver and does not materially affect recipient PT.