Hemostasis
Coagulation cascade, antiplatelet/anticoagulant pharmacology, factor deficiencies, transfusion reactions, vWD, HIT. ← Back to Q-Bank
Q1. Heparin mechanism
Heparin's anticoagulant effect is mediated through:
A. Direct thrombin inhibition
B. Binding to antithrombin → accelerates inactivation of thrombin (IIa), Xa, IXa, XIa, XIIa, VIIa
C. Activation of protein C
D. Inhibition of vitamin K-dependent γ-carboxylation
E. Platelet GPIIb/IIIa blockade
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Answer: B. Unfractionated heparin: binds AT → ~1000× acceleration of inactivation of multiple coagulation factors (predominantly IIa and Xa, equal effect). LMWH: predominantly Xa inhibition (less IIa). Fondaparinux: pure Xa inhibition via AT.
Q2. Heparin resistance
A patient receives 400 U/kg heparin before CPB but ACT remains 320 sec. The most likely cause is:
A. Pseudocholinesterase deficiency
B. Antithrombin III deficiency
C. Factor V Leiden
D. Vitamin K deficiency
E. Increased fibrinogen
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Answer: B. Heparin resistance = inadequate ACT response to heparin. Antithrombin III deficiency (hereditary or acquired from prolonged heparin exposure, ECMO, severe sepsis) is the classic cause. Treat with FFP (replaces AT) or AT concentrate, then re-dose heparin.
Q3. HIT diagnosis
A patient on heparin for 7 days develops platelet drop from 280k → 90k and new DVT. The next diagnostic test is:
A. Bone marrow biopsy
B. Platelet aggregation studies
C. ELISA for anti-PF4 antibodies followed by serotonin release assay for confirmation
D. Repeat CBC
E. D-dimer
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Answer: C. Suspect HIT (4T score): timing 5–10 days, platelet drop 30–50%, new thrombosis, no other cause. ELISA sensitive (rule out), serotonin release assay specific (confirm). Treat empirically pending tests: stop all heparin, start non-heparin anticoagulant (argatroban or fondaparinux). Don't transfuse platelets unless bleeding. Don't start warfarin until platelets recover >150k.
Q4. Argatroban half-life
Argatroban is the preferred direct thrombin inhibitor for HIT in patients with:
A. Renal failure
B. Hepatic failure
C. Critical illness with hepatic dysfunction
D. Cardiopulmonary bypass
E. Pregnancy
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Answer: A. Argatroban is hepatically cleared — preferred in renal failure (avoid in hepatic failure). Bivalirudin: ~80% spontaneous proteolysis + 20% renal — preferred in renal failure and ideal for CPB (short 25-min half-life). Lepirudin/hirudin: renal clearance, irreversible binding, long half-life.
Q5. Warfarin reversal — urgent surgery
A patient on warfarin (INR 4.5) requires emergent surgery within 4 hours. The most rapid reversal is:
A. Vitamin K 10 mg PO
B. Fresh frozen plasma 15 mL/kg
C. 4-factor prothrombin complex concentrate (PCC) + IV vitamin K 5–10 mg
D. Cryoprecipitate
E. Recombinant factor VIIa
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Answer: C. 4-factor PCC (KCentra, Beriplex) reverses warfarin in 15–30 min and has lower volume than FFP. Vitamin K (IV) ensures durable reversal (warfarin t½ ~40 hr; PCC effect lasts only 6–8 hr). FFP slower, larger volume, allergic risk.
Q6. Dabigatran reversal
A patient on dabigatran with intracerebral hemorrhage requires reversal. The most appropriate agent is:
A. Andexanet alfa
B. Idarucizumab (Praxbind)
C. PCC
D. FFP
E. Tranexamic acid
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Answer: B. Idarucizumab = monoclonal antibody fragment that binds dabigatran's active site (REVERSE-AD trial). Andexanet alfa reverses Xa inhibitors (apixaban, rivaroxaban). Dabigatran is dialyzable; apixaban and rivaroxaban are not.
Q7. Apixaban / Rivaroxaban reversal
A patient on rivaroxaban presents with major hemorrhage. The most specific reversal agent is:
A. Idarucizumab
B. Andexanet alfa
C. Protamine
D. Vitamin K
E. Cryoprecipitate
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Answer: B. Andexanet alfa is a recombinant factor Xa decoy that binds factor Xa inhibitors (apixaban, rivaroxaban, edoxaban). 4-factor PCC is alternative if andexanet unavailable. Not dialyzable.
Q8. Protamine dose
To reverse 30,000 units of heparin given for CPB, the initial protamine dose is approximately:
A. 50 mg
B. 100 mg
C. 200 mg
D. 300 mg
E. 500 mg
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Answer: D. 1 mg protamine reverses 100 U heparin. 30,000 U / 100 = 300 mg. Give slowly via peripheral line over 10–15 min to avoid hypotension/pulmonary HTN. Risk factors for reaction: prior NPH insulin, fish allergy, vasectomy, prior protamine exposure. Maximum dose ~500 mg.
Q9. Clopidogrel mechanism
Clopidogrel inhibits platelet aggregation by:
A. Inhibiting COX-1 irreversibly
B. Blocking the ADP P2Y12 receptor irreversibly
C. Blocking GPIIb/IIIa receptors
D. Inhibiting thromboxane A2
E. Direct thrombin inhibition
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Answer: B. Clopidogrel (and prasugrel, ticagrelor) block ADP-mediated platelet activation via P2Y12. Irreversible for clopidogrel/prasugrel; reversible for ticagrelor (must be dosed BID). Prodrug requiring CYP2C19 — poor metabolizers have reduced effect. Ticagrelor and prasugrel give more consistent platelet inhibition.
Q10. Aspirin mechanism
Aspirin's antiplatelet effect is mediated by:
A. Reversible COX-2 inhibition
B. Irreversible acetylation of COX-1 → no TXA₂ production for the lifetime of the platelet
C. P2Y12 blockade
D. GPIIb/IIIa blockade
E. Antithrombin acceleration
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Answer: B. Aspirin irreversibly acetylates COX in platelets → no new TXA₂ for 7–10 days (anucleate platelets can't synthesize new COX). Hemostasis returns in ~2–3 days as new platelets are produced. Other NSAIDs cause reversible inhibition. For emergent reversal: platelet transfusion.
Q11. GPIIb/IIIa inhibitors
Abciximab vs. eptifibatide/tirofiban: the most important difference is:
A. Abciximab is reversible; eptifibatide is irreversible
B. Abciximab is irreversible (24–48 hr to recover); eptifibatide/tirofiban are competitive reversible (~8 hr)
C. Abciximab is hepatically cleared
D. Tirofiban does not affect platelets
E. They have identical pharmacology
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Answer: B. Abciximab (ReoPro) — irreversible, recovery 24–48 hr. Eptifibatide (Integrilin), tirofiban (Aggrastat) — competitive, reversible, recovery ~8 hr. All can cause thrombocytopenia. Avoid neuraxial during therapeutic use.
Q12. von Willebrand disease types
The most common type of von Willebrand disease is:
A. Type 1 — partial quantitative deficiency
B. Type 2A — qualitative deficiency
C. Type 2B — gain of function with thrombocytopenia
D. Type 3 — total deficiency
E. Acquired vWD
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Answer: A. Type 1: ~70% of cases, autosomal dominant, partial quantitative deficiency. Type 2 (A/B/M/N): qualitative defects. Type 3: severe AR, almost no vWF. Treatment: DDAVP (releases endothelial vWF) — avoid in type 2B (induces thrombocytopenia). vWF concentrate (Humate-P) for severe disease or type 2B/3.
Q13. DDAVP mechanism
DDAVP (desmopressin) reduces bleeding by:
A. Activating fibrin formation
B. Releasing vWF and factor VIII from endothelial cells
C. Inhibiting fibrinolysis
D. Direct platelet activation
E. Suppressing protein C
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Answer: B. DDAVP stimulates V2 receptor → releases stored vWF and VIII from endothelium. Useful in type 1 vWD, mild hemophilia A, uremia-induced platelet dysfunction. Tachyphylaxis after repeat doses (~12 hr). Side effects: hyponatremia (structural similarity to ADH), water retention.
Q14. Hemophilia A factor
Hemophilia A is caused by deficiency of:
A. Factor VII
B. Factor VIII
C. Factor IX
D. Factor XI
E. von Willebrand factor
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Answer: B. Hemophilia A = factor VIII deficiency (X-linked). Hemophilia B = factor IX deficiency. Both have prolonged PTT correcting with mixing study (unless inhibitors). Treatment: factor concentrate; goal ≥40% activity preoperatively. ~10% develop inhibitors — manage with bypassing agents (FEIBA, recombinant VIIa) — hematology consult.
Q15. Factor V Leiden
Factor V Leiden causes thrombosis through:
A. Loss of factor V activity
B. Activated factor V resistant to inactivation by activated protein C
C. Vitamin K-dependent gamma-carboxylation defect
D. Increased fibrinogen
E. Decreased antithrombin
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Answer: B. Factor V Leiden = point mutation makes factor Va resistant to cleavage by APC. Most common inherited thrombophilia (~5% of Europeans heterozygous). Heterozygous: ~5× DVT risk; homozygous: ~50×. Lifelong anticoagulation considered after recurrent thromboses, life-threatening event, or with another prothrombotic mutation.
Q16. Antiphospholipid syndrome
Antiphospholipid syndrome is characterized by:
A. Bleeding tendency only
B. Arterial and venous thrombosis with characteristic prolonged aPTT that does not correct with mixing
C. Decreased fibrinogen
D. Inherited factor deficiency
E. Vitamin K deficiency
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Answer: B. APS: hypercoagulable state with venous/arterial thromboses and pregnancy losses. Diagnosis: clinical event + ≥1 of three antibodies (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein-1) on 2 occasions ≥12 weeks apart. aPTT prolonged (LA artifact) but bleeding does not occur from the lab abnormality. Lifelong anticoagulation.
Q17. TEG R-time
A prolonged R time on thromboelastography (TEG) is best treated with:
A. Platelet transfusion
B. Cryoprecipitate
C. Fresh frozen plasma
D. Tranexamic acid
E. Calcium
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Answer: C. TEG R time (reaction time): 1–6 min normally, reflects clotting factor initiation → FFP. K time and alpha angle: fibrinogen → cryoprecipitate. MA: platelet/fibrinogen-mediated clot strength → platelets. LY30 > 6% (teardrop shape): fibrinolysis → TXA/aminocaproic acid.
Q18. Tranexamic acid mechanism
Tranexamic acid reduces bleeding by:
A. Direct activation of antithrombin
B. Lysine analog that blocks plasmin binding to fibrin → inhibits fibrinolysis
C. Inhibition of factor Xa
D. Vasoconstriction
E. Platelet activation
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Answer: B. TXA and aminocaproic acid are lysine analogs that competitively bind plasminogen/plasmin lysine sites, preventing fibrin breakdown. Renally cleared — adjust in renal failure. Evidence: CRASH-2 (trauma), WOMAN (PPH), cardiac surgery. Give within 3 hr of bleeding onset for maximum benefit.
Q19. Cryoprecipitate contents
Cryoprecipitate contains all EXCEPT:
A. Fibrinogen
B. Factor VIII
C. Factor XIII
D. von Willebrand factor
E. Factor VII
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Answer: E. Cryo: fibrinogen, VIII, XIII, vWF, fibronectin. ~200 mg fibrinogen per unit (15 mL). 10 units (pooled) raises 70 kg patient's fibrinogen by ~70 mg/dL. Indicated for hypofibrinogenemia (<150–200), vWD without DDAVP response, hemophilia A. Factor VII is not in cryo.
Q20. FFP dose
The standard FFP dose for coagulopathy is:
A. 1 unit
B. 2 units
C. 10–15 mL/kg
D. 20 mL/kg
E. 50 mL/kg
Show answer
Answer: C. FFP 10–15 mL/kg raises factor levels by ~20%. Indications: PT/PTT >1.5×, warfarin reversal urgent (when PCC unavailable), AT deficiency, TTP (plasma exchange). Intrinsic FFP INR ~1.6–1.8 — won't correct below this.
Q21. Platelet transfusion threshold
A 50-year-old undergoing routine spinal surgery has a platelet count of 60. The platelet transfusion threshold is:
A. <10k for any patient
B. <20k if bleeding
C. <50k for most surgeries (higher 80–100k for neurosurgery, posterior fossa, intraocular)
D. <100k for all
E. Transfuse for any count <150k
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Answer: C. General threshold <50k for surgery; <80–100k for neurosurgery, posterior eye/spine cases; <20k for prophylaxis in non-bleeding patient. 1 unit apheresis platelets ~6 random donors → expected rise of 30k.
Q22. Lupus anticoagulant
Lupus anticoagulant on lab testing causes:
A. Bleeding tendency
B. Prolonged aPTT that does not correct with mixing study and represents a hypercoagulable state
C. Decreased fibrinogen
D. Hemolysis
E. Thrombocytopenia
Show answer
Answer: B. LA prolongs PT/PTT (binds phospholipid in the assay) but causes thrombosis, not bleeding. Seen in SLE, antiphospholipid syndrome, drug-induced (phenothiazines, hydralazine, phenytoin, quinine), infections, IBD. Confirm with dilute Russell viper venom time.
Q23. DIC labs
Disseminated intravascular coagulation classically shows:
A. Thrombocytopenia, elevated d-dimer, prolonged PT and PTT, low fibrinogen
B. Thrombocytosis with normal coagulation
C. Isolated low fibrinogen
D. Isolated thrombocytopenia
E. Elevated factor V only
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Answer: A. DIC: simultaneous bleeding + thrombosis from consumption of platelets and factors. Triggers: sepsis, trauma, malignancy, obstetric complications (placental abruption, AFE), hemolytic transfusion reactions. Schistocytes on smear. Treat the underlying cause; replace platelets, cryo (fibrinogen), FFP as needed.
Q24. ACT vs aPTT for CPB
The activated clotting time (ACT) is preferred over aPTT during CPB because:
A. ACT is more sensitive
B. ACT has a linear response between 1–5 U/mL heparin, while aPTT is unmeasurably prolonged above 1 U/mL
C. ACT is unaffected by hypothermia
D. ACT does not require blood sampling
E. ACT is cheaper
Show answer
Answer: B. ACT linear response 1–5 U/mL heparin; aPTT saturated. ACT is affected by hypothermia, hemodilution, thrombocytopenia, platelet inhibitors — but remains the standard for CPB heparin monitoring. ACT >400–480 sec required for CPB.
Q25. Vitamin K-dependent factors
The vitamin K-dependent coagulation factors are:
A. Factors II, V, VII, IX
B. Factors II, VII, IX, X, plus proteins C and S
C. Factors VIII, IX, XI, XII
D. Fibrinogen, prothrombin, plasminogen
E. Factor XIII only
Show answer
Answer: B. "1972" — factors II, VII, IX, X — plus proteins C and S. All require γ-carboxylation. Warfarin inhibits VKORC1 → reduces functional vitamin K. Initial pro-thrombotic state from short-half-life protein C and S → bridge with heparin to prevent warfarin-induced skin necrosis.
Q26. Bridge therapy
A patient with mechanical mitral valve on warfarin (target INR 2.5–3.5) needs elective cholecystectomy. The most appropriate periop plan is:
A. Continue warfarin
B. Stop warfarin 5 days preop, bridge with therapeutic LMWH, last dose 24 hr preop
C. Stop warfarin 1 day preop
D. Switch to aspirin
E. Stop warfarin 5 days preop, no bridging
Show answer
Answer: B. Mechanical mitral valve = high VTE risk → bridge with therapeutic LMWH. Stop warfarin 5 days preop, start LMWH after INR <2, last dose 24 hr preop, restart 24 hr postop (delay 48–72 hr in high-bleeding surgery). 2015 BRIDGE trial: routine bridging for AFib increased bleeding without thromboembolic benefit — bridging selective to highest-risk patients.
Q27. Glanzmann thrombasthenia
Glanzmann thrombasthenia is characterized by deficiency of:
A. GPIb-IX-V (vWF receptor)
B. GPIIb/IIIa (fibrinogen receptor)
C. von Willebrand factor
D. Factor VIII
E. Plasma cholinesterase
Show answer
Answer: B. Glanzmann: GPIIb/IIIa deficiency → impaired platelet aggregation. Bernard-Soulier: GPIb deficiency → impaired platelet adhesion to vWF. Both AR, mucocutaneous bleeding. Treat with platelet transfusion; recombinant VIIa for refractory bleeding (antibodies to transfused platelets common).
Q28. Pregnancy and coagulation
Pregnancy alters coagulation by:
A. Decreasing fibrinogen
B. Hypercoagulable state with elevated fibrinogen and factors V, VII, VIII, IX, X, XII; decreased XI, XIII, antithrombin
C. Bleeding tendency
D. Decreased platelets without cause
E. Decreased factor VIII
Show answer
Answer: B. Pregnancy = hypercoagulable. Fibrinogen normally rises to 400–600 mg/dL by term. PT and PTT shorten ~20%. Mild thrombocytopenia common (gestational thrombocytopenia). VTE risk increased throughout pregnancy and peaks postpartum.
Q29. Cell salvage contraindications
Intraoperative cell salvage is contraindicated in:
A. Cardiac surgery
B. Major orthopedic surgery
C. Surgical field contamination with malignancy, infection, or amniotic fluid (relative — leukocyte depletion filter may mitigate)
D. Trauma surgery
E. Vascular surgery
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Answer: C. Traditional contraindications: bowel contamination, malignancy, amniotic fluid. Modern leukocyte depletion filters and irradiation may mitigate — current evidence supports use even in cesarean section and cancer surgery. Avoid with topical hemostatic agents (Avitene, Surgicel may cause hypotension if reinfused).
Q30. Massive transfusion electrolyte
After receiving 12 units of pRBCs in 4 hours, a patient develops tetany and prolonged QT. The most likely cause is:
A. Hyperkalemia
B. Hypocalcemia from citrate binding
C. Hypomagnesemia
D. Hyperphosphatemia
E. Hypoglycemia
Show answer
Answer: B. Citrate in stored blood binds ionized calcium → hypocalcemia. Sodium citrate is also metabolized to bicarbonate → metabolic alkalosis (especially >8 units). Other massive transfusion complications: hyperkalemia (especially with old blood or rapid transfusion), hypothermia, dilutional coagulopathy, hyperphosphatemia, hypomagnesemia. Replace calcium with 1 g calcium chloride or 3 g calcium gluconate per 3–4 units.
Q31. Fibrinogen replacement
For a patient with active hemorrhage and fibrinogen 80 mg/dL, the most appropriate replacement is:
A. FFP 2 units
B. Cryoprecipitate 10 units (raises fibrinogen ~70 mg/dL) OR fibrinogen concentrate (RiaSTAP)
C. Platelets
D. Whole blood
E. Tranexamic acid alone
Show answer
Answer: B. Target fibrinogen >150–200 mg/dL in active hemorrhage (>200 in OB). Cryoprecipitate or fibrinogen concentrate. Fibrinogen concentrate has lower transfusion-related risk and faster availability than cryo.