WBR0880

Author	[[PageAuthor::Serge Korjian M.D. (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Physiology
Sub Category	SubCategory::Hematology
Prompt	[[Prompt::A 56-year-old man is admitted to the hospital for severe angina, dyspnea, and diaphoresis. His initial labs are significant for elevated troponins. The man undergoes emergent PCI and is discharged home the second day on dual antiplatelet therapy consisting of aspirin and clopidogrel. Which of the following steps in primary hemostasis is inhibited by aspirin and clopidogrel respectively?]]
Answer A	AnswerA::vWF binding GpIb, ADP release
Answer A Explanation	AnswerAExp::Neither of these mechanisms is inhibited by aspirin or clopidogrel.
Answer B	AnswerB::vWF binding collagen, GpIIbIIIa expression
Answer B Explanation	AnswerBExp::Although clopidogrel inhibits GpIIbIIIa expression by blocking ADP receptors, aspirin doesn't inhibit vWF binding to collagen.
Answer C	AnswerC::Thromboxane A2 release, GpIIbIIIa binding fibrinogen
Answer C Explanation	AnswerCExp::Although aspirin blocks thromboxane A2 release, clopidogrel does not inhibit GpIIbIIIa binding fibrinogen. C
Answer D	AnswerD::Thromboxane A2 release, GpIIbIIIa expression
Answer D Explanation	AnswerDExp::Aspirin inhibits thromboxane A2 release while clopidogrel blocks GpIIbIIIa expression.
Answer E	AnswerE::Thromboxane A2 release, ADP release
Answer E Explanation	AnswerEExp::Although aspirin blocks thromboxane A2 release, clopidogrel does not inhibit ADP release. Clopidogrel is responsible for blocking the ADP receptors that mediate GpIIbIIIa expression.
Right Answer	RightAnswer::D
Explanation	[[Explanation::Dual antiplatelet therapy is the standard of care in patients undergoing percutaneous coronary intervention (PCI) with stent placement. Aspirin in combination with clopidogrel is one of the combinations that is most commonly used. Aspirin is an irreversible inhibitor of both COX1 and COX2 which has analgesic, anti-inflammatory, and antiplatelet (mostly at low doses) characteristics. Aspirin decreases thromboxane A2 production leading to a decrease in platelet aggregation. Clopidogrel on the other hand is an ADP receptor blocker that inhibits ADP mediated expression of GpIIb/IIIa on the surface of platelets required to bind fibrinogen. Antiplatelet therapy is essential after stent placement due the risk of associated in-stent thrombosis that often leads to death or a large myocardial infarctions. Stent thrombosis occurs due to several factors including patient- and lesion-related factors, as well as the thrombogenicity of the stent itself. Educational Objective: Both aspirin and clopidogrel play a role in decreasing platelet aggregation, aspirin via decreasing thromboxane A2 and clopidogrel via blocking ADP receptors and decreasing GpIIbIIIa expression. References: Savi P, Nurden P, Nurden AT, Levy-toledano S, Herbert JM. Clopidogrel: a review of its mechanism of action. Platelets. 1998;9(3-4):251-5. Vane J, Botting R. The mechanism of action of aspirin. Thrombosis Research. 2003;110(5-6):255-258.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Clopidogrel, WBRKeyword::Aspirin, WBRKeyword::Primary hemostasis, WBRKeyword::GpIIbIIIa, WBRKeyword::Platelets, WBRKeyword::Thromboxane
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