A bleeding patient has impaired platelet attachment to exposed subendothelium despite a normal platelet count. Which protein is most directly deficient?

A. von Willebrand factor
B. Protein C cofactor
C. Antithrombin III
D. Tissue plasminogen activator

A. von Willebrand factor

A deep vascular laceration exposes tissue factor to circulating blood. Which pair is ultimately generated downstream?

A. Plasmin and protein C
B. Fibrinogen and prekallikrein
C. Albumin and ceruloplasmin
D. Thrombin and factor XIII

D. Thrombin and factor XIII

Which pair of coagulation proteins primarily serves as binding proteins?

A. II and X
B. V and VIII
C. VII and IX
D. XI and XII

B. V and VIII

A patient with severe chronic liver failure has reduced synthesis of the most important serum protein. Which protein is it?

A. Haptoglobin
B. Transferrin
C. Albumin
D. Ceruloplasmin

C. Albumin

A monoclonal spike on serum electrophoresis reflects proliferation of which immunoglobulin-secreting cell?

A. Plasma cell
B. Kupffer cell
C. Mast cell
D. Megakaryocyte

A. Plasma cell

Failure of which plasma system most directly impairs clearance of circulating antigen-antibody complexes?

A. Kallikrein system
B. Complement system
C. Fibrinolytic system
D. Contact pathway

B. Complement system

Which combination can activate complement in the way described here?

A. Heparin and platelet factor 4
B. Thrombin and fibrin monomers
C. Collagen and dense granules
D. Immune complexes and bacterial polysaccharides

D. Immune complexes and bacterial polysaccharides

The major serine protease inhibitor of human plasma is:

A. C1 esterase inhibitor
B. Alpha-2 macroglobulin
C. α1-antitrypsin
D. Tissue factor inhibitor

C. α1-antitrypsin

Which amino acid residue is necessary for α1-antitrypsin binding to proteases?

A. Methionine 358
B. Glycine 202
C. Lysine 72
D. Tyrosine 110

A. Methionine 358

Markedly decreased hepatic secretion of α1-antitrypsin is most likely due to:

A. Promoter methylation
B. Intron 1 deletion
C. Frameshift in exon 2
D. Point mutation in exon 5

D. Point mutation in exon 5

A patient develops antibodies against platelet glycoproteins with no discernible cause. Which diagnosis best fits?

A. Hemolytic uremic syndrome
B. Idiopathic thrombocytopenic purpura
C. Bernard-Soulier syndrome
D. Disseminated intravascular coagulation

B. Idiopathic thrombocytopenic purpura

Which substance is characteristically stored in platelet electron-dense granules?

A. Platelet-derived growth factor
B. von Willebrand factor
C. Serotonin
D. Hydrolytic enzymes

C. Serotonin

Which molecule is a classic constituent of platelet α-granules?

A. Fibrinogen
B. ATP
C. Calcium
D. Serotonin

A. Fibrinogen

Platelet lysosomal granules characteristically contain:

A. ADP and ATP
B. Fibrinogen and vWF
C. Calcium and serotonin
D. Hydrolytic enzymes

D. Hydrolytic enzymes

Which set lists the three fundamental platelet mechanisms in coagulation?

A. Activation, inhibition, lysis
B. Adhesion, aggregation, secretion
C. Binding, cleavage, diffusion
D. Vasoconstriction, repair, lysis

B. Adhesion, aggregation, secretion

A patient lacking von Willebrand factor would rapidly clear which coagulation factor from plasma?

A. Factor V
B. Factor VII
C. Factor VIII
D. Factor XIII

C. Factor VIII

Binding of collagen to platelet glycoprotein GPIa most directly causes which change?

A. Disk-to-sphere transformation
B. Immediate plasmin formation
C. Complement complex assembly
D. vWF proteolytic cleavage

A. Disk-to-sphere transformation

Binding of subendothelial vWF to platelet GPIb most directly exposes binding sites for:

A. Collagen and thrombin
B. ADP and serotonin
C. Albumin and transferrin
D. Fibrinogen and vWF

D. Fibrinogen and vWF

An inherited mutation in platelet GPIb causes which disorder?

A. Glanzmann thrombasthenia
B. Bernard-Soulier syndrome
C. Idiopathic thrombocytopenia purpura
D. Thrombotic thrombocytopenic purpura

B. Bernard-Soulier syndrome

Familial TTP is most closely associated with mutation of which enzyme?

A. Platelet cyclooxygenase
B. Factor VIII cofactor
C. vWF-specific metalloprotease
D. Platelet fibrinogen receptor

C. vWF-specific metalloprotease

ADP released from activated platelets most directly promotes further exposure of:

A. GPIIb/IIIa binding sites
B. Tissue factor molecules
C. Factor XIII cross-links
D. Lysosomal hydrolases

A. GPIIb/IIIa binding sites

The α and β peptides of fibrinogen are held together primarily by:

A. Ionic interactions
B. Hydrogen bonds
C. Ester linkages
D. Disulfide bonds

D. Disulfide bonds

A patient has an isolated defect in a coagulation enzyme class shared by factors VII, IX, X, XI, and prothrombin. Which class is affected?

A. Serine proteases
B. Calcium-binding cofactors
C. Fibrin cross-linkers
D. Platelet glycoproteins

A. Serine proteases

Which pair functions primarily as cofactor binding proteins within the coagulation cascade?

A. II and X
B. VII and IX
C. XI and XIII
D. V and VIII

D. V and VIII

In response to collagen and thrombin, activated platelets release which prominent vasoconstrictor pair?

A. ADP and fibrinogen
B. Serotonin and thromboxane A2
C. vWF and PDGF
D. ATP and calcium

B. Serotonin and thromboxane A2

A patient forms unstable clots that fail to become covalently cross-linked. Which factor normally acts as a Ca2+-dependent transglutaminase?

A. Factor V
B. Factor VIII
C. Factor XIII
D. Factor XI

C. Factor XIII

Which sequence best describes the key steps of the extrinsic pathway?

A. VII binds tissue factor, activates X
B. X binds collagen, activates IX
C. XI activates IX, then VIII
D. XII binds platelets, activates X

A. VII binds tissue factor, activates X

During fibrin stabilization, factor XIIIa catalyzes which reaction between fibrin monomers?

A. Hydrolysis of lysine-serine bonds
B. Oxidation of methionine residues
C. Transamidation of glutamine and lysine
D. Carboxylation of aspartate residues

C. Transamidation of glutamine and lysine

Which activated coagulation factor is the only enzyme in the cascade that is not a serine protease?

A. Factor XIIIa
B. Factor Xa
C. Factor VIIa
D. Thrombin

A. Factor XIIIa

A patient on a vitamin K antagonist will produce reduced amounts of which gamma-carboxylated factor set?

A. V, VIII, XI, XIII
B. I, V, VIII, XII
C. II, VII, IX, X
D. VIII, IX, XI, XII

C. II, VII, IX, X

Gamma-carboxyglutamate residues allow certain factors to form coordination complexes with Ca2+. Which pair is specifically listed?

A. Factor VII and IX
B. Factor X and prothrombin
C. Factor V and VIII
D. Factor XI and XIII

B. Factor X and prothrombin

Warfarin most directly impairs gamma-carboxylation of which anticoagulant pair in addition to clotting factors?

A. Protein C and protein S
B. Antithrombin and heparin cofactor
C. Plasminogen and fibrinogen
D. Thrombomodulin and tissue factor

A. Protein C and protein S

A mutation disrupts assembly of the prothrombinase complex by altering a cofactor that binds Xa and prothrombin. Which factor is affected?

A. Factor VIIIa
B. Factor XIIIa
C. Factor Va
D. Factor VIIa

C. Factor Va

Vitamin K is functionally active in which chemical form?

A. Quinone form
B. Hydroquinone form
C. Epoxide form
D. Aldehyde form

B. Hydroquinone form

The enzyme targeted by warfarin is best identified as:

A. Vitamin K epoxide reductase
B. Gamma-glutamyl carboxylase
C. Tissue factor protease
D. Thrombomodulin reductase

A. Vitamin K epoxide reductase

Which group is activated by thrombin in its prothrombotic regulatory role?

A. II, VII, X
B. VIII, IX, XIII
C. V, VIII, XI
D. Protein C, protein S, XII

C. V, VIII, XI

Which action directly promotes clot formation by thrombin?

A. Activating plasmin from plasminogen
B. Cleaving factor XIII to XIIIa
C. Inhibiting release of factor VIII
D. Destroying factors Va and VIIIa

B. Cleaving factor XIII to XIIIa

Thrombin produces antithrombotic effects after binding to:

A. von Willebrand factor
B. Antithrombin III
C. Heparan sulfate
D. Thrombomodulin

D. Thrombomodulin

Binding of thrombin to thrombomodulin leads to activation of which anticoagulant?

A. Protein S
B. Protein C
C. Factor V
D. Plasmin

B. Protein C

A neonate with a homozygous defect dies early from severe thrombotic disease. Deficiency of which pair is most consistent with this presentation?

A. Factors V and VIII
B. Factors IX and X
C. Protein C and protein S
D. Antithrombin and fibrinogen

C. Protein C and protein S

The activated protein C complex exerts anticoagulant effects by destroying which factors?

A. Va and VIIIa
B. VIIa and IXa
C. XIa and XIIIa
D. IIa and Xa

A. Va and VIIIa

A patient with inherited thrombophilia has factor V Leiden. Which amino acid substitution is classically present?

A. Glycine to serine
B. Lysine to methionine
C. Tyrosine to cysteine
D. Arginine to glutamine

D. Arginine to glutamine

A young adult with inherited thrombophilia develops a postoperative leg clot. Which condition is most strongly associated with Factor V Leiden?

A. Deep venous thrombosis
B. Hemophilia A bleeding
C. Bernard-Soulier syndrome
D. Thrombotic thrombocytopenic purpura

A. Deep venous thrombosis

Activity of thrombin is primarily restrained by which serpin?

A. Protein C
B. Antithrombin III
C. Alpha-2 antiplasmin
D. Tissue factor pathway inhibitor

B. Antithrombin III

Formation of the antithrombin III-thrombin complex involves which residue pair?

A. Serine on thrombin
B. Glutamine on thrombin
C. Lysine on thrombin
D. Tyrosine on thrombin

A. Serine on thrombin

Formation of the antithrombin III-thrombin complex involves which residue pair? (second pair)

A. Lysine on antithrombin
B. Arginine on antithrombin
C. Histidine on antithrombin
D. Cysteine on antithrombin

B. Arginine on antithrombin

Heparin accelerates antithrombin III activity by binding primarily to which residue on antithrombin III?

A. Lysine
B. Arginine
C. Serine
D. Glutamate

A. Lysine

The antithrombin III-heparin complex can directly inactivate which factor?

A. Factor VIIa
B. Activated protein C
C. Factor VIIIa
D. Factor Xa

D. Factor Xa

Which coagulation-related protein is not inactivated by the antithrombin III-heparin complex?

A. Factor IXa
B. Factor XIa
C. Factor VIIa
D. Factor Xa

C. Factor VIIa

Healthy endothelial cells reduce platelet aggregation by synthesizing which pair?

A. TXA2 and serotonin
B. PGI2 and nitric oxide
C. ADP and thrombin
D. Fibrinogen and vWF

B. PGI2 and nitric oxide

Which enzyme directly cleaves fibrin during fibrinolysis?

A. Plasmin
B. Thrombin
C. Kallikrein
D. Factor XIIIa

A. Plasmin

In addition to suppressing coagulation, activated protein C promotes fibrinolysis by stimulating release of:

A. Thrombomodulin
B. von Willebrand factor
C. Tissue plasminogen activator
D. Platelet factor 4

C. Tissue plasminogen activator

Circulating plasmin is rapidly neutralized by which inhibitor?

A. Alpha-1 antitrypsin
B. Alpha-2 antiplasmin
C. Antithrombin III
D. Protein S

B. Alpha-2 antiplasmin

A boy with hemarthroses has classic hemophilia A. Which factor is deficient?

A. Factor IX
B. Factor VIII
C. Factor XI
D. Factor XIII

B. Factor VIII

A patient with hemophilia B most likely has a mutation in which factor?

A. Factor V
B. Factor VIII
C. Factor IX
D. Factor X

C. Factor IX

A point mutation R98W in VKORC1 is associated with which disorder?

A. Hemophilia B
B. Bernard-Soulier syndrome
C. Glanzmann thrombasthenia
D. VKCFD2

D. VKCFD2

Clopidogrel and ticagrelor inhibit platelet aggregation by blocking which receptor?

A. GPIIb/IIIa receptor
B. PAR-1 receptor
C. P2Y12 receptor
D. GPIb receptor

C. P2Y12 receptor

A patient with severe hypoalbuminemia develops dependent edema despite normal cardiac function. Which plasma protein role is most directly impaired?

A. Maintaining plasma oncotic pressure
B. Cross-linking fibrin polymers
C. Activating platelet P2Y12 receptors
D. Cleaving fibrin during lysis

A. Maintaining plasma oncotic pressure

A patient with thrombocytopenia continues to ooze from a small vascular injury. Which normal platelet function is most immediately lost?

A. Mechanical plug formation
B. Fibrin monomer degradation
C. Vitamin K regeneration
D. Gamma-carboxylation of factors

A. Mechanical plug formation

Platelets become activated after binding to a site of vascular injury. What is the most important immediate consequence?

A. Reduced local vasoconstriction
B. Increased platelet aggregation
C. Decreased fibrinogen binding
D. Inhibition of thrombin formation

B. Increased platelet aggregation

At the site of endothelial injury, circulating fibrinogen most directly binds to:

A. Resting erythrocyte membranes
B. Activated platelets
C. Soluble albumin complexes
D. Endothelial thrombomodulin

B. Activated platelets

Normal hemostasis requires tight regulation of clotting primarily to prevent:

A. Polycythemia and leukopenia
B. Thrombosis and bleeding
C. Hypertension and bradycardia
D. Acidosis and hypoxemia

B. Thrombosis and bleeding

The clotting cascade is best described as a sequence of events leading to activation of:

A. Plasmin
B. Fibrinogen
C. Thrombin
D. Albumin

C. Thrombin

A patient has impaired conversion of fibrinogen into fibrin during clot formation. Which enzyme is most directly deficient?

A. Thrombin
B. Plasmin
C. Protein C
D. Antithrombin III

A. Thrombin

A newly formed soft clot fails to become a stable hard clot. Which thrombin-dependent process is most likely defective?

A. Platelet serotonin release
B. Fibrin cross-linking
C. Protein S degradation
D. Plasminogen activation

B. Fibrin cross-linking

Proteins C and S act together to regulate coagulation after being activated by:

A. Fibrinogen
B. Heparin
C. Thrombin
D. Plasmin

C. Thrombin

To assemble clotting complexes on activated platelets, certain factors require gamma-carboxyglutamate residues primarily to bind:

A. Sodium and fibrin
B. Calcium and membranes
C. Albumin and collagen
D. Plasmin and heparin

B. Calcium and membranes

Antithrombin III is best classified as which type of regulatory molecule?

A. Serine protease inhibitor
B. Platelet adhesion receptor
C. Vitamin K reductase
D. Fibrin cross-linking enzyme

A. Serine protease inhibitor

Which protease is uniquely capable of dissolving an established fibrin clot?

A. Thrombin
B. Factor Xa
C. Plasmin
D. Factor XIIIa

C. Plasmin

A boy with recurrent hemarthroses is missing an essential factor for thrombin activation. Which diagnosis best fits?

A. Hemophilia A
B. Bernard-Soulier syndrome
C. Factor V Leiden
D. Idiopathic thrombocytopenia purpura

A. Hemophilia A