Hemostasis
Coagulation cascade, antiplatelet/anticoagulant pharmacology, factor deficiencies, transfusion reactions, vWD, HIT. ← All topics
Q1. Heparin mechanism
Heparin's anticoagulant effect is mediated through:
A. Direct thrombin inhibition without requiring cofactors
B. Binding to antithrombin and accelerating inactivation of coagulation factors
C. Activation of protein C leading to degradation of factors Va and VIIIa
D. Inhibition of vitamin K-dependent γ-carboxylation of clotting factors
E. Platelet GPIIb/IIIa receptor blockade preventing fibrinogen cross-linking
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Answer: B. Unfractionated heparin binds to antithrombin (AT) and accelerates the inactivation of multiple coagulation factors by approximately 1000-fold. The primary targets are thrombin (factor IIa) and factor Xa, with equal effect on both, though factors IXa, XIa, XIIa, and VIIa are also inactivated. Low molecular weight heparin (LMWH) predominantly inhibits factor Xa with less effect on thrombin. Fondaparinux provides pure factor Xa inhibition via antithrombin binding. Direct thrombin inhibitors like dabigatran work without requiring antithrombin as a cofactor. Warfarin inhibits vitamin K-dependent γ-carboxylation. Protein C activation is the mechanism of activated protein C (drotrecogin alfa). GPIIb/IIIa blockade is the mechanism of antiplatelet agents like abciximab.
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 from genetic polymorphism or acquired liver disease
B. Antithrombin III deficiency from hereditary causes or prolonged heparin exposure
C. Factor V Leiden mutation causing activated protein C resistance
D. Vitamin K deficiency from malnutrition or warfarin therapy
E. Increased fibrinogen levels from acute phase reaction or inflammatory state
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Answer: B. Heparin resistance is defined as inadequate ACT response despite appropriate heparin dosing. Antithrombin III (AT III) deficiency is the classic cause because heparin requires AT III as a cofactor to exert its anticoagulant effect. AT III deficiency can be hereditary or acquired from prolonged heparin exposure, ECMO, severe sepsis, nephrotic syndrome, or liver disease. Treatment consists of administering fresh frozen plasma (which replaces antithrombin) or antithrombin concentrate, followed by re-dosing heparin. Pseudocholinesterase deficiency affects succinylcholine and ester local anesthetic metabolism but not coagulation. Factor V Leiden causes hypercoagulability through resistance to activated protein C but does not impair heparin action. Vitamin K deficiency affects synthesis of factors II, VII, IX, and X but does not cause heparin resistance. Elevated fibrinogen is a prothrombotic state but does not interfere with heparin's mechanism of action.
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 to evaluate for primary marrow disorder causing thrombocytopenia and thrombosis
B. Platelet aggregation studies to assess for inherited platelet dysfunction contributing to thrombotic events
C. ELISA for anti-PF4 antibodies followed by serotonin release assay for confirmation if positive
D. Repeat CBC in 24 hours to confirm persistent thrombocytopenia and rule out laboratory error
E. D-dimer assay to quantify fibrin degradation products and assess for ongoing thrombotic activity
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Answer: C. This patient meets criteria for suspected HIT based on the 4T score: appropriate timing (5–10 days after heparin initiation), significant platelet drop (>50% from baseline, from 280k to 90k representing a 68% decrease), new thrombosis (DVT), and no other obvious cause. The diagnostic approach uses a two-step algorithm: ELISA for anti-PF4 antibodies is highly sensitive and serves to rule out HIT if negative, while the serotonin release assay is highly specific and confirms the diagnosis when positive. Treatment should begin empirically while awaiting test results: immediately stop all heparin products (including flushes), start a non-heparin anticoagulant such as argatroban or fondaparinux, avoid platelet transfusions unless active bleeding occurs, and do not start warfarin until platelet count recovers above 150,000/μL to prevent venous limb gangrene and warfarin-induced skin necrosis.
Q4. Argatroban half-life
Argatroban is the preferred direct thrombin inhibitor for HIT in patients with:
A. Renal failure, because argatroban is hepatically cleared and does not require dose adjustment
B. Hepatic failure, because argatroban undergoes spontaneous proteolysis independent of liver function
C. Critical illness with hepatic dysfunction, because argatroban has a short half-life during shock
D. Cardiopulmonary bypass, because argatroban is rapidly cleared by the extracorporeal circuit filters
E. Pregnancy, because argatroban has minimal placental transfer and no teratogenic effects documented
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Answer: A. Argatroban is hepatically cleared and is the preferred direct thrombin inhibitor in patients with renal failure because it does not require dose adjustment in this setting. It should be avoided in hepatic failure. Bivalirudin undergoes approximately 80% spontaneous proteolysis and 20% renal clearance, making it preferred in renal failure and ideal for cardiopulmonary bypass due to its short 25-minute half-life. Lepirudin and hirudin are renally cleared, have irreversible binding, and have long half-lives, making them problematic in renal dysfunction.
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 alone, which reverses warfarin effect within 12–24 hours
B. Fresh frozen plasma 15 mL/kg alone, which reverses warfarin effect within 6–12 hours
C. 4-factor prothrombin complex concentrate with IV vitamin K 5–10 mg for rapid reversal
D. Cryoprecipitate 10 units, which replaces fibrinogen and select clotting factors for hemostasis
E. Recombinant factor VIIa alone, which bypasses warfarin-inhibited factors for immediate hemostasis
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Answer: C. 4-factor prothrombin complex concentrate (PCC) such as KCentra or Beriplex reverses warfarin anticoagulation within 15–30 minutes by directly replacing vitamin K-dependent clotting factors (II, VII, IX, X). This is the most rapid method for emergent reversal. IV vitamin K (5–10 mg) must be given concurrently to ensure durable reversal, because warfarin has a half-life of approximately 40 hours while PCC's effect lasts only 6–8 hours. Fresh frozen plasma works more slowly (6–12 hours), requires large volumes (15 mL/kg), and carries higher risks of transfusion reactions and volume overload. Oral vitamin K takes 12–24 hours to be effective. Cryoprecipitate does not contain adequate amounts of the vitamin K-dependent factors needed for warfarin reversal. Recombinant factor VIIa is not standard therapy for warfarin reversal and is reserved for refractory bleeding in specific circumstances.
Q6. Dabigatran reversal
A patient on dabigatran with intracerebral hemorrhage requires reversal. The most appropriate agent is:
A. Andexanet alfa, a recombinant factor Xa decoy that reverses factor Xa inhibitors
B. Idarucizumab, a monoclonal antibody fragment that binds dabigatran's active site
C. Prothrombin complex concentrate, a four-factor concentrate that replaces clotting factors
D. Fresh frozen plasma, a blood product containing all coagulation factors
E. Tranexamic acid, an antifibrinolytic agent that inhibits plasminogen activation
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Answer: B. Idarucizumab (Praxbind) is a monoclonal antibody fragment that specifically binds dabigatran's active site, providing rapid and complete reversal. This was demonstrated in the REVERSE-AD trial. Andexanet alfa is the specific reversal agent for factor Xa inhibitors such as apixaban and rivaroxaban, not for dabigatran. An important clinical distinction is that dabigatran is dialyzable due to its low protein binding, whereas apixaban and rivaroxaban are not dialyzable. Prothrombin complex concentrate and fresh frozen plasma may be considered when specific reversal agents are unavailable, but they are not first-line for dabigatran reversal. Tranexamic acid is an antifibrinolytic that does not reverse anticoagulation.
Q7. Apixaban / Rivaroxaban reversal
A patient on rivaroxaban presents with major hemorrhage. The most specific reversal agent is:
A. Idarucizumab, a monoclonal antibody fragment that binds dabigatran
B. Andexanet alfa, a recombinant factor Xa decoy protein
C. Protamine sulfate, a heparin-binding cationic polypeptide
D. Vitamin K, a cofactor for hepatic clotting factor synthesis
E. Cryoprecipitate, a plasma-derived concentrate of fibrinogen
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Answer: B. Andexanet alfa is a recombinant modified factor Xa decoy protein that specifically binds and reverses factor Xa inhibitors including rivaroxaban, apixaban, and edoxaban. It acts as a competitive inhibitor by binding these anticoagulants in the plasma. Four-factor prothrombin complex concentrate (4-factor PCC) is an alternative reversal agent if andexanet alfa is unavailable. Factor Xa inhibitors are not dialyzable. Idarucizumab is specific for dabigatran reversal. Protamine reverses heparin. Vitamin K reverses warfarin but takes hours to work. Cryoprecipitate provides fibrinogen but does not reverse anticoagulants.
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. The standard protamine dosing ratio is 1 mg protamine reverses 100 units of heparin. For 30,000 units of heparin given during cardiopulmonary bypass, the calculation is 30,000 units divided by 100, which equals 300 mg of protamine. Protamine should be administered slowly via peripheral line over 10 to 15 minutes to avoid hypotension and pulmonary hypertension. Risk factors for protamine reactions include prior NPH insulin use, fish allergy, vasectomy, and prior protamine exposure. The maximum recommended dose is approximately 500 mg.
Q9. Clopidogrel mechanism
Clopidogrel inhibits platelet aggregation by:
A. Inhibiting cyclooxygenase-1 irreversibly
B. Blocking the ADP P2Y12 receptor irreversibly
C. Blocking glycoprotein IIb/IIIa receptors competitively
D. Inhibiting thromboxane A2 synthesis irreversibly
E. Directly inhibiting thrombin at active site
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Answer: B. Clopidogrel blocks ADP-mediated platelet activation via the P2Y12 receptor, and does so irreversibly (unlike ticagrelor, which is reversible and must be dosed twice daily). Clopidogrel is a prodrug requiring CYP2C19 activation; poor metabolizers have reduced antiplatelet effect. Prasugrel also irreversibly blocks P2Y12 but provides more consistent platelet inhibition than clopidogrel. Aspirin irreversibly inhibits COX-1. Abciximab and eptifibatide block GPIIb/IIIa receptors. Dabigatran is a direct thrombin inhibitor.
Q10. Aspirin mechanism
Aspirin's antiplatelet effect is mediated by:
A. Reversible acetylation of COX-2 in platelets preventing thromboxane A₂ synthesis
B. Irreversible acetylation of COX-1 in platelets preventing thromboxane A₂ synthesis
C. Irreversible blockade of P2Y12 receptors preventing ADP-mediated platelet activation
D. Reversible blockade of GPIIb/IIIa receptors preventing platelet aggregation and adhesion
E. Irreversible binding to antithrombin III accelerating inactivation of thrombin
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Answer: B. Aspirin irreversibly acetylates COX-1 in platelets, preventing new thromboxane A₂ (TXA₂) synthesis for the lifetime of the platelet (7–10 days). Because platelets are anucleate, they cannot synthesize new COX enzyme. Hemostasis returns in approximately 2–3 days as new platelets are produced by the bone marrow. Other NSAIDs cause reversible COX inhibition. For emergent reversal of aspirin's antiplatelet effect, platelet transfusion is required. COX-2 is not the primary target for aspirin's antiplatelet effect. P2Y12 blockade describes clopidogrel and ticagrelor. GPIIb/IIIa blockade describes abciximab and eptifibatide. Antithrombin acceleration describes heparin's mechanism.
Q11. GPIIb/IIIa inhibitors
Abciximab vs. eptifibatide/tirofiban: the most important difference is:
A. Abciximab is reversible with recovery in 8 hours; eptifibatide is irreversible with recovery in 24–48 hours
B. Abciximab is irreversible with recovery in 24–48 hours; eptifibatide/tirofiban are reversible with recovery in 8 hours
C. Abciximab is hepatically cleared with renal excretion; eptifibatide/tirofiban are cleared by biliary excretion only
D. Abciximab affects both platelets and endothelium; tirofiban affects only endothelium without affecting platelet function
E. Abciximab and eptifibatide/tirofiban have identical pharmacology with the same recovery time of 12–24 hours
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Answer: B. Abciximab (ReoPro) is an irreversible GPIIb/IIIa inhibitor with platelet function recovery taking 24–48 hours. Eptifibatide (Integrilin) and tirofiban (Aggrastat) are competitive, reversible inhibitors with recovery in approximately 8 hours. This difference in reversibility and recovery time is the most clinically important distinction between these agents. All GPIIb/IIIa inhibitors can cause thrombocytopenia, and neuraxial anesthesia should be avoided during therapeutic use of any of these drugs.
Q12. von Willebrand disease types
The most common type of von Willebrand disease is:
A. Type 1 — partial quantitative deficiency, autosomal dominant inheritance
B. Type 2A — qualitative deficiency, abnormal multimer assembly pattern
C. Type 2B — gain of function mutation, associated thrombocytopenia
D. Type 3 — complete quantitative deficiency, autosomal recessive inheritance
E. Acquired vWD — antibody-mediated deficiency, associated lymphoproliferative disorders
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Answer: A. Type 1 von Willebrand disease accounts for approximately 70% of all cases and represents a partial quantitative deficiency of von Willebrand factor with autosomal dominant inheritance. Type 2 variants (2A, 2B, 2M, 2N) are qualitative defects affecting vWF function. Type 2A involves abnormal multimer assembly, while type 2B is a gain-of-function mutation causing increased platelet binding and thrombocytopenia. Type 3 is a severe autosomal recessive form with almost complete absence of vWF. Acquired vWD can occur with lymphoproliferative disorders or other conditions. Treatment includes DDAVP, which releases endothelial vWF stores, though it should be avoided in type 2B as it can worsen thrombocytopenia. vWF concentrate (Humate-P) is used for severe disease or types 2B and 3.
Q13. DDAVP mechanism
DDAVP (desmopressin) reduces bleeding by:
A. Activating fibrin formation through thrombin enhancement
B. Releasing von Willebrand factor and factor VIII from endothelial cells
C. Inhibiting fibrinolysis by blocking plasminogen activator
D. Direct platelet activation through glycoprotein IIb/IIIa receptors
E. Suppressing protein C activity and reducing anticoagulation
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Answer: B. DDAVP (desmopressin) works by stimulating V2 receptors on endothelial cells, which triggers the release of stored von Willebrand factor (vWF) and factor VIII from Weibel-Palade bodies. This mechanism makes it useful in type 1 von Willebrand disease, mild hemophilia A, and uremia-induced platelet dysfunction. Tachyphylaxis occurs after repeat doses (approximately 12 hours). Important side effects include hyponatremia and water retention due to its structural similarity to ADH (antidiuretic hormone). DDAVP does not directly activate fibrin formation, inhibit fibrinolysis, activate platelets directly, or suppress protein C.
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 is caused by factor VIII deficiency and is X-linked. Hemophilia B is caused by factor IX deficiency. Both hemophilias present with prolonged PTT that corrects with mixing study unless inhibitors are present. Treatment involves factor concentrate with a goal of at least 40% activity preoperatively. Approximately 10% of patients develop inhibitors, which are managed with bypassing agents such as FEIBA or recombinant factor VIIa, and require hematology consultation. Factor VII deficiency causes a different coagulopathy with isolated prolonged PT. Factor XI deficiency is a milder bleeding disorder also called hemophilia C. Von Willebrand factor deficiency causes von Willebrand disease, which has a different presentation and inheritance pattern than hemophilia A.
Q15. Factor V Leiden
Factor V Leiden causes thrombosis through:
A. Loss of factor V activity leading to impaired cofactor function
B. Activated factor V resistant to inactivation by activated protein C
C. Vitamin K-dependent gamma-carboxylation defect affecting multiple coagulation factors
D. Increased fibrinogen levels resulting in enhanced clot formation
E. Decreased antithrombin activity impairing natural anticoagulation
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Answer: B. Factor V Leiden is a point mutation that makes factor Va resistant to cleavage by activated protein C (APC). This is the most common inherited thrombophilia, affecting approximately 5% of Europeans in the heterozygous state. Heterozygous carriers have roughly 5-fold increased risk of deep vein thrombosis, while homozygous individuals have approximately 50-fold increased risk. Lifelong anticoagulation is considered after recurrent thromboses, life-threatening thrombotic events, or when combined with another prothrombotic mutation. The other options represent different mechanisms: loss of factor V activity would cause bleeding rather than thrombosis, vitamin K-dependent carboxylation defects affect factors II, VII, IX, and X, elevated fibrinogen is a weak risk factor for thrombosis but not the mechanism of Factor V Leiden, and decreased antithrombin is a separate inherited thrombophilia.
Q16. Antiphospholipid syndrome
Antiphospholipid syndrome is characterized by:
A. Bleeding tendency with prolonged aPTT that corrects with mixing studies
B. Arterial and venous thrombosis with prolonged aPTT that does not correct with mixing
C. Decreased fibrinogen levels with prolonged PT that corrects with mixing studies
D. Inherited factor deficiency with prolonged aPTT that corrects with mixing studies
E. Vitamin K deficiency with prolonged PT that corrects with vitamin K administration
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Answer: B. Antiphospholipid syndrome is a hypercoagulable state characterized by venous and arterial thromboses as well as pregnancy losses. Diagnosis requires a clinical event plus at least one of three antibodies (lupus anticoagulant, anticardiolipin, or anti-β2-glycoprotein-1) detected on two separate occasions at least 12 weeks apart. The lupus anticoagulant causes a paradoxical prolongation of the aPTT in vitro, but this is a laboratory artifact and does not cause clinical bleeding. The prolonged aPTT does not correct with mixing studies because the antibody interferes with phospholipid-dependent coagulation tests. Despite the prolonged aPTT, patients are actually prothrombotic and require lifelong anticoagulation after a thrombotic event.
Q17. TEG R-time
A prolonged R time on thromboelastography (TEG) is best treated with:
A. Platelet transfusion to restore clot strength and platelet function
B. Cryoprecipitate to correct fibrinogen deficiency and improve polymerization
C. Fresh frozen plasma to replace deficient clotting factors
D. Tranexamic acid to inhibit fibrinolysis and stabilize clot
E. Calcium chloride to reverse citrate toxicity and enhance coagulation
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Answer: C. TEG R time (reaction time) normally ranges from 1 to 6 minutes and reflects the initiation phase of clotting, which depends on clotting factor activity. A prolonged R time indicates clotting factor deficiency and is best treated with fresh frozen plasma (FFP), which contains all clotting factors. Other TEG parameters guide different therapies: K time and alpha angle reflect fibrinogen function and are corrected with cryoprecipitate; maximum amplitude (MA) reflects platelet-mediated and fibrinogen-mediated clot strength and is treated with platelet transfusion when platelets are deficient; LY30 greater than 6 percent (teardrop shape) indicates fibrinolysis and is treated with antifibrinolytics such as tranexamic acid or aminocaproic acid.
Q18. Tranexamic acid mechanism
Tranexamic acid reduces bleeding by:
A. Direct activation of antithrombin, enhancing its inhibitory effect on thrombin
B. Lysine analog that blocks plasmin binding to fibrin, inhibiting fibrinolysis
C. Inhibition of factor Xa, preventing conversion of prothrombin to thrombin
D. Vasoconstriction at the site of bleeding, reducing local blood flow
E. Platelet activation and aggregation, promoting formation of platelet plug
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Answer: B. Tranexamic acid and aminocaproic acid are lysine analogs that competitively bind to lysine-binding sites on plasminogen and plasmin, preventing these molecules from binding to fibrin and thereby inhibiting fibrinolysis. TXA is renally cleared, so dose adjustment is needed in renal failure. Evidence for its use comes from CRASH-2 (trauma), WOMAN (postpartum hemorrhage), and cardiac surgery trials. Maximum benefit is achieved when TXA is given within 3 hours of bleeding onset.
Q19. Cryoprecipitate contents
Cryoprecipitate contains all EXCEPT:
A. Fibrinogen, which is present at approximately 200 mg per unit
B. Factor VIII, which is concentrated during the freezing process
C. Factor XIII, which is retained in the precipitate fraction
D. von Willebrand factor, which coprecipitates with Factor VIII
E. Factor VII, which remains in the supernatant after precipitation
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Answer: E. Cryoprecipitate contains fibrinogen, Factor VIII, Factor XIII, von Willebrand factor, and fibronectin. Each unit (approximately 15 mL) contains about 200 mg of fibrinogen. When 10 units are pooled and administered, they raise a 70 kg patient's fibrinogen level by approximately 70 mg/dL. Cryoprecipitate is indicated for hypofibrinogenemia (fibrinogen less than 150 to 200 mg/dL), von Willebrand disease without response to DDAVP, and hemophilia A. Factor VII is not present in cryoprecipitate because it does not precipitate during the cold thawing process and remains in the supernatant plasma fraction instead.
Q20. FFP dose
The standard FFP dose for coagulopathy is:
A. 1 unit per transfusion episode
B. 2 units per transfusion episode
C. 10–15 mL/kg per transfusion episode
D. 20 mL/kg per transfusion episode
E. 50 mL/kg per transfusion episode
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Answer: C. The standard FFP dose for coagulopathy is 10–15 mL/kg, which raises coagulation factor levels by approximately 20%. This dose typically corresponds to 4–6 units in an average adult. Common indications include PT/PTT greater than 1.5 times normal, urgent warfarin reversal when prothrombin complex concentrate is unavailable, antithrombin deficiency, and TTP requiring plasma exchange. It is important to note that FFP has an intrinsic INR of 1.6–1.8, so it cannot correct the INR below this baseline level. Single-unit or 2-unit dosing is generally insufficient to achieve meaningful correction of coagulopathy. Doses of 20 mL/kg or 50 mL/kg exceed standard recommendations and risk volume overload without proportional benefit.
Q21. Platelet transfusion threshold
A 50-year-old undergoing routine spinal surgery has a platelet count of 60. The platelet transfusion threshold is:
A. <10,000/μL for any patient regardless of bleeding status or planned procedure
B. <20,000/μL for patients with active bleeding or hemorrhagic complications
C. <50,000/μL for most surgeries and <80,000–100,000/μL for neurosurgical procedures
D. <100,000/μL for all surgical procedures including minor and superficial operations
E. <150,000/μL for any patient with platelet count below normal reference range
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Answer: C. The general platelet transfusion threshold is <50,000/μL for most surgical procedures. However, higher thresholds of 80,000–100,000/μL are recommended for neurosurgery, posterior fossa surgery, spinal procedures, and intraocular surgery due to the higher risk of catastrophic bleeding in these confined spaces. For non-bleeding patients, prophylactic transfusion is typically considered at <20,000/μL. One unit of apheresis platelets (equivalent to approximately 6 random donor units) typically raises the platelet count by about 30,000/μL. In this case, the patient with a count of 60,000/μL undergoing spinal surgery falls below the recommended threshold and would benefit from platelet transfusion.
Q22. Lupus anticoagulant
Lupus anticoagulant on lab testing causes:
A. Bleeding tendency due to impaired platelet function and clotting factor inhibition
B. Prolonged aPTT that does not correct with mixing study and represents hypercoagulable state
C. Decreased fibrinogen levels secondary to increased consumption and impaired hepatic synthesis
D. Hemolysis with elevated lactate dehydrogenase and indirect bilirubin and decreased haptoglobin
E. Thrombocytopenia with platelet counts below 100,000 and increased risk of mucosal bleeding
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Answer: B. Lupus anticoagulant prolongs PT/PTT by binding phospholipid in the assay, but paradoxically causes thrombosis rather than bleeding, representing a hypercoagulable state. The prolonged aPTT does not correct with mixing studies because the lupus anticoagulant is an antibody, not a factor deficiency. It is seen in systemic lupus erythematosus, antiphospholipid syndrome, drug-induced cases (phenothiazines, hydralazine, phenytoin, quinine), infections, and inflammatory bowel disease. Confirmation is obtained with dilute Russell viper venom time. Despite the name "anticoagulant," patients are at increased risk for arterial and venous thrombosis.
Q23. DIC labs
Disseminated intravascular coagulation classically shows:
A. Thrombocytopenia, elevated d-dimer, prolonged PT and PTT, low fibrinogen
B. Thrombocytosis, decreased d-dimer, shortened PT and PTT, elevated fibrinogen
C. Thrombocytopenia, normal d-dimer, normal PT and PTT, elevated fibrinogen
D. Normal platelet count, elevated d-dimer, prolonged PT only, normal fibrinogen
E. Thrombocytopenia, decreased d-dimer, normal PT and PTT, normal fibrinogen
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Answer: A. DIC is characterized by simultaneous bleeding and thrombosis from consumption of platelets and clotting factors. The classic laboratory pattern includes thrombocytopenia (platelet consumption), elevated d-dimer (reflecting fibrinolysis of microthrombi), prolonged PT and PTT (consumption of clotting factors), and low fibrinogen (consumption and conversion to fibrin). Common triggers include sepsis, trauma, malignancy, and obstetric complications such as placental abruption, amniotic fluid embolism, and hemolytic transfusion reactions. Schistocytes are often seen on peripheral blood smear due to microangiopathic hemolytic anemia. Treatment focuses on addressing the underlying cause while providing supportive care with platelet transfusion, cryoprecipitate for fibrinogen replacement, and fresh frozen plasma as needed.
Q24. ACT vs aPTT for CPB
The activated clotting time (ACT) is preferred over aPTT during CPB because:
A. ACT provides a more sensitive measurement of coagulation status than aPTT during cardiac surgery
B. ACT has a linear response between 1–5 U/mL heparin while aPTT becomes unmeasurably prolonged above 1 U/mL
C. ACT remains unaffected by hypothermia and hemodilution unlike aPTT which is significantly altered by temperature
D. ACT does not require blood sampling and can be performed using point-of-care devices at the bedside
E. ACT is cheaper to perform and requires less specialized laboratory equipment than aPTT for routine monitoring
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Answer: B. The ACT has a linear response in the therapeutic range of 1–5 U/mL heparin, which corresponds to the high-dose heparin used during cardiopulmonary bypass. In contrast, aPTT becomes unmeasurably prolonged (saturated) above 1 U/mL heparin, making it useless for monitoring the much higher heparin levels required for CPB. While ACT is affected by hypothermia, hemodilution, thrombocytopenia, and platelet inhibitors, it remains the standard for CPB heparin monitoring. An ACT greater than 400–480 seconds is typically required before initiating CPB.
Q25. Vitamin K-dependent factors
The vitamin K-dependent coagulation factors are:
A. Factors II, V, VII, and IX
B. Factors II, VII, IX, and X, plus proteins C and S
C. Factors VIII, IX, XI, and XII
D. Factors I, II, and V, plus plasminogen
E. Factors XI, XII, and XIII, plus protein S
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Answer: B. The vitamin K-dependent coagulation factors are II, VII, IX, and X, plus proteins C and S. A useful mnemonic is "1972" for factors II, VII, IX, and X. All six of these factors require γ-carboxylation of glutamic acid residues for proper function. Warfarin inhibits vitamin K epoxide reductase complex 1 (VKORC1), which reduces functional vitamin K and impairs synthesis of these factors. Because proteins C and S have shorter half-lives than the procoagulant factors II, VII, IX, and X, warfarin initially creates a transient prothrombotic state. This is why heparin bridging is necessary to prevent warfarin-induced skin necrosis during initiation of therapy.
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 throughout the perioperative period without interruption
B. Stop warfarin 5 days preop, bridge with therapeutic LMWH, last dose 24 hr preop
C. Stop warfarin 1 day preop and resume on postoperative day 1
D. Switch to aspirin 325 mg daily starting 5 days before surgery
E. Stop warfarin 5 days preop without bridging anticoagulation, resume postop
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Answer: B. Mechanical mitral valve represents high thromboembolic risk and requires bridging anticoagulation. The appropriate strategy is to stop warfarin 5 days preoperatively, start therapeutic LMWH once INR falls below 2, give the last LMWH dose 24 hours before surgery, and restart anticoagulation 24 hours postoperatively (or delay 48–72 hours for high-bleeding-risk procedures). Continuing warfarin risks surgical bleeding. Stopping warfarin only 1 day preoperatively is insufficient time for INR normalization. Aspirin alone does not provide adequate anticoagulation for mechanical valves. Not bridging exposes the patient to unacceptable thrombotic risk. The 2015 BRIDGE trial showed that routine bridging for atrial fibrillation increased bleeding without reducing thromboembolism, but mechanical valves (especially mitral) remain a high-risk indication where bridging is still recommended.
Q27. Glanzmann thrombasthenia
Glanzmann thrombasthenia is characterized by deficiency of:
A. GPIb-IX-V complex, the receptor for von Willebrand factor
B. GPIIb/IIIa complex, the receptor for fibrinogen during aggregation
C. von Willebrand factor, the multimeric protein mediating adhesion
D. Factor VIII, the coagulation factor bound to vWF
E. Plasma cholinesterase, the enzyme that hydrolyzes succinylcholine
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Answer: B. Glanzmann thrombasthenia is caused by deficiency of the GPIIb/IIIa complex (the fibrinogen receptor), resulting in impaired platelet aggregation. In contrast, Bernard-Soulier syndrome is caused by GPIb-IX-V deficiency, resulting in impaired platelet adhesion to von Willebrand factor. Both are autosomal recessive disorders that present with mucocutaneous bleeding. Treatment includes platelet transfusion for acute bleeding, though antibodies to transfused platelets commonly develop. Recombinant factor VIIa can be used for refractory bleeding when platelet transfusions are ineffective.
Q28. Pregnancy and coagulation
Pregnancy alters coagulation by:
A. Decreasing fibrinogen, factors V, VII, VIII, IX, X, XII and increasing antithrombin levels
B. Increasing fibrinogen, factors V, VII, VIII, IX, X, XII and decreasing factors XI, XIII, antithrombin
C. Increasing factors XI and XIII while decreasing fibrinogen, factors VII, VIII, and antithrombin
D. Decreasing fibrinogen, factors VII, VIII, X, XII and increasing factors V, XI, XIII, antithrombin
E. Increasing antithrombin, factors XI, XIII while decreasing fibrinogen and factors V, VII, VIII, IX, X
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Answer: B. Pregnancy produces a hypercoagulable state. Fibrinogen normally rises to 400–600 mg/dL by term (compared to non-pregnant levels of 200–400 mg/dL). Factors V, VII, VIII, IX, X, and XII are elevated, while factors XI and XIII are decreased. Antithrombin levels decrease. PT and PTT shorten by approximately 20%. Mild thrombocytopenia is common (gestational thrombocytopenia). VTE risk is increased throughout pregnancy and peaks in the postpartum period. This hypercoagulable state helps prevent excessive bleeding at delivery but increases thrombotic risk.
Q29. Cell salvage contraindications
Intraoperative cell salvage is contraindicated in:
A. Cardiac surgery with cardiopulmonary bypass and systemic heparinization
B. Major orthopedic surgery with cemented or uncemented joint arthroplasty
C. Surgical field contamination with malignancy, infection, or amniotic fluid
D. Trauma surgery with massive hemorrhage requiring massive transfusion protocol
E. Vascular surgery with aortic cross-clamping and supraceliac or infrarenal exposure
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Answer: C. Traditional contraindications to intraoperative cell salvage include bowel contamination, malignancy, and amniotic fluid. These are now considered relative contraindications rather than absolute, as modern leukocyte depletion filters and irradiation may mitigate risks. Current evidence supports use even in cesarean section and cancer surgery. Cell salvage should be avoided when topical hemostatic agents such as Avitene or Surgicel have been used, as reinfusion may cause hypotension. Cardiac surgery, major orthopedic surgery, trauma surgery, and vascular surgery are all appropriate settings for cell salvage use.
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 from release of intracellular potassium in stored red blood cells
B. Hypocalcemia from citrate anticoagulant binding ionized calcium in stored blood
C. Hypomagnesemia from dilutional effects and inadequate replacement during massive transfusion
D. Hyperphosphatemia from release of intracellular phosphate in stored red blood cells
E. Hypoglycemia from inadequate dextrose administration and increased metabolic demands
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Answer: B. Citrate anticoagulant in stored blood binds ionized calcium, causing hypocalcemia. This presents with tetany, paresthesias, and prolonged QT interval, as seen in this patient. Sodium citrate is also metabolized to bicarbonate, which can cause metabolic alkalosis, especially after transfusion of more than 8 units. Calcium should be replaced with 1 g calcium chloride or 3 g calcium gluconate per 3–4 units of blood products. Other massive transfusion complications include hyperkalemia (especially with old blood or rapid transfusion), hypothermia, dilutional coagulopathy, hyperphosphatemia, and hypomagnesemia. While hyperkalemia causes peaked T waves and shortened QT, and hypomagnesemia can prolong QT, neither typically causes tetany in this setting. Hyperphosphatemia and hypoglycemia do not present with this constellation of findings.
Q31. Fibrinogen replacement
For a patient with active hemorrhage and fibrinogen 80 mg/dL, the most appropriate replacement is:
A. FFP 2 units to provide clotting factors and fibrinogen
B. Cryoprecipitate 10 units or fibrinogen concentrate (RiaSTAP)
C. Platelets 1 apheresis unit to improve clot formation
D. Whole blood 2 units to replace all blood components
E. Tranexamic acid alone to inhibit fibrinolysis and bleeding
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Answer: B. Target fibrinogen is greater than 150–200 mg/dL in active hemorrhage (greater than 200 mg/dL in obstetric hemorrhage). This patient with fibrinogen 80 mg/dL requires an increase of approximately 70–120 mg/dL. Cryoprecipitate 10 units typically raises fibrinogen by approximately 70 mg/dL, making it appropriate for this scenario. Fibrinogen concentrate (RiaSTAP) is an alternative that offers lower transfusion-related risk and faster availability than cryoprecipitate. FFP contains fibrinogen but in much lower concentrations (approximately 2 mg/mL) and would require large volumes to achieve target levels. Platelets contain minimal fibrinogen. Whole blood provides some fibrinogen but is not the most concentrated source. Tranexamic acid is an antifibrinolytic that helps stabilize clot but does not replace depleted fibrinogen.