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Part II: Hemostasis and Thrombosis

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What is the primary molecular event underlying platelet aggregation and propagation of the platelet plug?

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A. Binding of vWF to platelet GPIb complex

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B. Binding of vWF to platelet GPIIb/IIIa

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C. Binding of fibrin to platelet GPIb complex

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D. Binding of fibrinogen to platelet GPIb complex

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E. Binding of fibrinogen to platelet GPIIb/IIIa

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Upon activation of the platelet, a receptor for fibrinogen is uncovered. This large bivalent ligand can then bind to another activated platelet, eventually forming a three-dimensional network (i.e., the “platelet plug”). The platelet is tethered to the injured blood vessel wall by the even larger von Willebrand factor (vWF) protein, which also has a domain that binds to collagen. (The answer is E.)

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What is the primary role of tissue factor?

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A. Activation of prothrombin

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B. Activation of factor VII

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C. Activation of factor X

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D. Activation of thrombin

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E. All of the above

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Among the zymogens in the coagulation cascade, tissue factor activates only factor VII. Tissue factor is released at sites of trauma and is the primary initiator of the cascade in vivo. (The answer is B.)

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Which of the following proteins strengthens the fibrin clot by mediating covalent cross-linking?

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A. Thrombin

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B. Fibrinogen

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C. Factor Va

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D. Factor VIIa

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E. Factor XIIIa

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Activated factor XIII functions as a transglutaminase catalyzing the formation of covalent glutamyl-lysyl amide crosslinks between molecules of fibrin, resulting in a considerable strengthening of the clot. (The answer is E.)

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A 4-year-old boy has had recurrent bleeding episodes in his joints (hemarthroses). His maternal uncle has a similar history. Laboratory evaluation of both the boy and his uncle reveals normal platelet counts, prolonged partial thromboplastin times (PTTs), prolonged prothrombin times (PTs), and normal thrombin times. Among the possibilities listed below, these two patients are most likely to be deficient in:

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A. Fibrinogen

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B. Factor V

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C. Factor VIII

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D. Factor IX

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