Hemostasis Flashcards
In a patient with low von Willebrand factor, what other factor do you expect to be low?
Factor VIII
Explanation: Factor VIII binds to and is stabilized by von Willebrand factor.
What 3 key things are released from Weibel-Palade bodies by activated endothelium, and what is the role of each in hemostasis?
Endothelin: Vasoconstrictor
P-selectin: A lectin that binds to white blood cells and platelets and mediates adhesion to the endothelium
von Willebrand factor: Mediates platelet adherence and aggregation (binds GP Ib-V-IX)
Which of the following best represents the three steps of normal hemostasis in the correct order?
A. Decreased heart rate, adhesion of platelets, platelet aggregation
B. Increased blood flow, redness, swelling
C. Vascular damage, stasis, endothelial injury
D. Fibrin formation, vasoconstriction, inflammation
E. Vasoconstriction, platelet aggregation, fibrin formation
Which of the following best represents the three steps of normal hemostasis in the correct order?
A. Decreased heart rate, adhesion of platelets, platelet aggregation
B. Increased blood flow, redness, swelling
C. Vascular damage, stasis, endothelial injury
D. Fibrin formation, vasoconstriction, inflammation
E. Vasoconstriction, platelet aggregation, fibrin formation
Explanation: The sequence of normal hemostasis is the following:
Vasoconstriction is the immediate constriction of the vessel that reduces blood flow to the injured area mediated by reflex neurogenic mechanisms and the secretion of local factors such as endothelin.
Primary hemostasis is the formation of the platelet plug. Endothelium disruption exposes von Willebrand factor and collagen in the subendothelium which promotes platelet adherence and activation.
Secondary hemostasis is the deposition of fibrin to consolidate the platelet plug. Tissue factor is present in subendothelial cells in the vessel wall (in smooth muscle cells and fibroblasts). Exposure of tissue factor triggers the coagulation cascade which leads to thrombin formation. Thrombin cleaves fibrinogen into fibrin.
What is d-dimer and how is it produced?
D-dimer is a degradation product of cross-linked fibrin that is found in the blood after a blood clot has formed and then been degraded by plasmin-mediated fibrinolysis. D-dimer contains two cross-linked D domains of the fibrinogen protein. D-dimers can only be formed AFTER fibrinogen has been cross-linked to fibrin by the coagulation cascade.
What is the role of matrix metalloproteinases (MMPs) in contributing to atherosclerotic plaque rupture?
Matrix metalloproteinases produced by inflammatory cells weaken the overlying fibrous cap. The weakness of an atherosclerotic plaque is more critical than the size of the plaque in determining the chance of rupture.
What underlying factor must be present for the development of atherosclerosis?
Chronic inflammation is critical for the development of atherosclerosis. Oxidized low density lipoprotein (LDL) is the most commonly recognized mediator of inflammation in atherosclerosis, but it is ultimately the inflammation itself that leads to atherosclerosis. The inability to resolve the inflammation can lead to progressive plaque development.
What is a “fatty streak” in atherosclerosis formation?
A. Dystrophic calcification
B. Fibrous cap of collagen
C. Necrotic core of cellular debris
D. Subintimal accumulation of lipid-laden macrophages
E. Thrombus that develops after plaque rupture
What is a “fatty streak” in atherosclerosis formation?
A. Dystrophic calcification
B. Fibrous cap of collagen
C. Necrotic core of cellular debris
D. Subintimal accumulation of lipid-laden macrophages
E. Thrombus that develops after plaque rupture
Explanation: The “fatty streak” is an early lesion in atherosclerosis composed of chronic inflammatory cells (macrophages) that accumulate between the intima and media of arteries and ingest lipid to become foam cells. These lesions may regress (if inflammation resolves) or progress to mature atherosclerotic lesions. The fibrous cap (B) of vascular smooth muscle cells forming collagen and the necrotic core of debris (C) are part of a maturing lesion. Dystrophic calcification (A) and thrombus afer plaque rupture (E) are part of complicated atherosclerotic plaques.
GpIIb-IIIa on the platelet surface binds to which of the following?
A. von Willebrand factor
B. Fibrinogen
C. Subendothelium
D. Collagen
GpIIb-IIIa on the platelet surface binds to which of the following?
A. von Willebrand factor
B. Fibrinogen
C. Subendothelium
D. Collagen
Explanation: GpIIb-IIIa binds to fibrinogen to mediate formation of the platelet plug. Activation of GpIIb-IIIa increases its affinity for fibrinogen. Gp1b-V-IX binds to von Willebrand factor and Gp Ia-IIa and GpVI bind to collagen. Binding to both collagen and VWF mediate binding to the subendothelium.
Laboratory studies demonstrate a patient has a prolonged PT, but a normal PTT. Deficiency of which factor would produce these findings?
A. Factor II
B. Factor V
C. Factor VII
D. Factor X
E. Factor XIII
Laboratory studies demonstrate a patient has a prolonged PT, but a normal PTT. Deficiency of which factor would produce these findings?
A. Factor II
B. Factor V
C. Factor VII
D. Factor X
E. Factor XIII
Explanation: The PT measures the extrinsic pathway and the PTT measures the intrinsic pathway. The only factor that is part of the extrinsic pathway and not the intrinsic pathway is factor VII. Both tests evaluate the common pathway (X, V, II, and fibrinogen).
What is the first diagnostic laboratory test to order in evaluating a patient presenting with petechiae, purpura, and gingival bleeding?
Platelet count. The findings are suggestive of low platelets and/or platelet function abnormalities. Prior to ordering platelet function studies, a platelet count should be obtained as a low platelet count can present with similar findings to platelet function abnormalities.
A 6-year-old boy falls on the playground and approximately one hour later develops a large ecchymoses with swelling of the knee joint. His mother feels the bruise and swelling are disproportionate to the relatively minor fall. These findings are most suggestive of which of the following?
A. Platelet function defect
B. Coagulation factor deficiency
C. Aspirin effect
D. Low platelets
A 6-year-old boy falls on the playground and approximately one hour later develops a large ecchymoses with swelling of the knee joint. His mother feels the bruise and swelling are disproportionate to the relatively minor fall. These findings are most suggestive of which of the following?
A. Platelet function defect
B. Coagulation factor deficiency
C. Aspirin effect
D. Low platelets
Explanation: Although there is overlap in clinical presentation between primary and secondary hemostasis abnormalities, primary hemostasis defects of platelets (A or D) typically present with mucocutaneous bleeding (epistaxis, petechiae, etc.). Aspirin effect (which inhibits platelet activation and aggregation (C)) would be simlar to a primary hemostasis defect. Slightly delayed large ecchymoses and joint bleeding after trauma are suggestive of a defect in secondary hemostasis, which suggests a possible deficiency of a coagulation factor (B).
What is the common mechanism of action of fondaparinux and low molecular weight heparin and how do they differ?
Fondaparinux and low molecular weight heparin (LMWH) are anti-coagulants that mediate their effect by binding to anti-thrombin and increasing its ability to inhibit the coagulation factors, particulary Xa. While both drugs act by inhibiting factor Xa, fondaparinux is different from LMWH in that fondaparinux is more specific for inhibition of Xa. LMWH is also a weak inhibitor of thrombin.
Gamma-carboxylation of which of the following would be inhibited by warfarin?
A. Factor V
B. Factor VII
C. Factor VIII
D. Factor XIII
Gamma-carboxylation of which of the following would be inhibited by warfarin?
A. Factor V
B. Factor VII
C. Factor VIII
D. Factor XIII
Explanation: Warfarin is an oral anti-coagulant that inhibits the reduction of Vitamin K and prevents its activation. Activated Vitamin K is required for the gamma-carboxylation and synthesis of Factors VII, IX, X, prothrombin, and proteins C, S, and Z.
A 68-year-old man had a recent stroke. He is now on a program of diet and exercise and is taking clopidogrel antiplatelet medication to prevent a recurrent event.
Which feature regarding clopidogrel therapy is correct?
A. The drug irreversibly inhibits platelet cyclooxygenase.
B. The drug must be metabolized to an active form.
C. Combination therapy with aspirin is not effective in prevention of thromboses.
D. The drug inhibits GpIIb/IIIa receptors.
A 68-year-old man had a recent stroke. He is now on a program of diet and exercise and is taking clopidogrel antiplatelet medication to prevent a recurrent event.
Which feature regarding clopidogrel therapy is correct?
A. The drug irreversibly inhibits platelet cyclooxygenase.
B. The drug must be metabolized to an active form.
C. Combination therapy with aspirin is not effective in prevention of thromboses.
D. The drug inhibits GpIIb/IIIa receptors.
Explanation: Clopidogrel (Plavix) is a P2Y12 ADP receptor blocking agent that has to be metabolized to an active form to be effective (B). Choice A is incorrect as aspirin irreversibly inhibits cyclooxygenase. Choice C is incorrect as clopidogrel is often used in combination with aspirin to prevent recurrent ischemic events. Choice D is incorrect as drugs such as abciximab, eptifibatide, and tirofiban inhibit GpIIb/IIIa function.
