WBR0349

Author	[[PageAuthor::Serge Korjian M.D. (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathophysiology, MainCategory::Pharmacology
Sub Category	SubCategory::Hematology
Prompt	[[Prompt::A 23-year-old woman is brought to the emergency department after consuming rat poison in a suicide attempt. On arrival, EMS inform the staff of several episode of hematemesis on the way to the hospital. The patient is found to be hypotensive and tachycardic with altered mental status. Which of the following mechanisms is responsible for this patient's presentation?]]
Answer A	AnswerA::Inhibition of epoxide reductase
Answer A Explanation	AnswerAExp::Rodenticides are derivatives of coumarin and inhibit epoxide reductase leading to a decrease in clotting factors.
Answer B	AnswerB::Activation of plasminogen
Answer B Explanation	AnswerBExp::Fibrinolytics typically cause activation of plasminogen. Rat poison works by a different mechanism.
Answer C	AnswerC::Activation of antithrombin III
Answer C Explanation	AnswerCExp::Heparin causes activation of antithrombin III. Rat poison works by a different mechanism.
Answer D	AnswerD::Inhibition of GpIIbIIIa expression
Answer D Explanation	AnswerDExp::ADP receptor blockers such as clopidogrel cause inhibition of GpIIbIIIa expression. Rat poison works by a different mechanism.
Answer E	AnswerE::Inhibition of thromboxane A2 production
Answer E Explanation	AnswerEExp::Aspirin inhibits thromboxane A2 production leading to a decrease in platelet aggregation.
Right Answer	RightAnswer::A
Explanation	[[Explanation::Rodenticides, or rat poisons are a variety of agents used to exterminate rodents. The most commonly used rodenticides are anticoagulants typically of the coumarin class notably warfarin, coumatetralyl, difenacoum, and brodifacoum. They are also known as superwarfarins due to their substituted phenyl groups replacing the terminal methyl groups, that make these agents approximately 100 times more potent than regular coumarins. These agents act as they would for therapeutic purposes by inhibiting the gamma-carboxylation of coagulation factors that requires vitamin K. Coumarins inhibit the enzyme epoxide reductase that forms the active vitamin K needed for carboxylation. Blood levels of factors II, VII, IX and X drop to dangerously low levels after ingestion of large doses of rat poison usually leading to massive GI bleeding that may manifest as hematemesis. Treatment for early ingestion includes immediate gastric lavage. For late cases presenting with massive bleeding, treatment is typically with fresh frozen plasma and vitamin K administration. Educational Objective: The most common types of rat poison are anticoagulants from the coumarin family that inhibit epoxide reductase and lead to a decrease in clotting factors. References: Spahr JE, Maul JS, Rodgers GM. Superwarfarin poisoning: a report of two cases and review of the literature. Am J Hematol. 2007;82(7):656-60.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Rat poison, WBRKeyword::Vitamin K, WBRKeyword::Fresh frozen plasma, WBRKeyword::Epoxide reductase, WBRKeyword::Poisoning
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