WBR0784

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::Cardiology, SubCategory::Hematology
Prompt	[[Prompt::A 54-year-old woman presents to the emergency department 1 week after being discharged for the management of decompensated heart failure secondary to atrial fibrillation. The patient was discharged on warfarin and metoprolol and was doing well at home. This time the patient presents for painful and enlarging reddish-black lesions on either side of her abdomen (shown below). She describes that the lesions were initially painful but was only slightly eryhtematous. As they enlarged, they became darker, harder and unbearably painful. She denies any fever, chills, shortness of breath, or focal neurologic symptoms. Which of the following conditions is most likely associated with this patient’s presentation? ]]
Answer A	AnswerA::Factor V Leiden
Answer A Explanation	[[AnswerAExp::Factor V Leiden is a mutant that cannot be inactivated by protein C. It usually leads to a hypercoagulable state but is not associated with warfarin skin necrosis.]]
Answer B	AnswerB::Prothrombin gene mutation
Answer B Explanation	AnswerBExp::Prothrombin gene mutations usually predispose to increase in plasma levels of prothrombin and increase in the risk of venous clots. Is not associated with increased risk for warfarin skin necrosis.
Answer C	AnswerC::Antithrombin deficiency
Answer C Explanation	AnswerCExp::Antithrombin deficiency decreases the effectiveness of heparin usually minimizing the increase in PTT. Is not associated with increased risk for warfarin skin necrosis.
Answer D	AnswerD::Protein C deficiency
Answer D Explanation	[[AnswerDExp::Protein C deficiency predisposes to warfarin skin necrosis since protein C and S decrease much more rapidly than clotting factors after warfarin administration.]]
Answer E	AnswerE::Factor IX deficiency
Answer E Explanation	AnswerEExp::Factor IX deficiency is seen in patients with Hemophilia A. Patients are at risk for hemarthrosis and heavy bleeding after trauma.
Right Answer	RightAnswer::D
Explanation	[[Explanation::Warfarin is an oral anticoagulant used in several hypercoagulable states as well as in patients with atrial fibrillation to decrease the risk of clot formation. Protein C and S are important anticoagulant molecules that inactivate factors V and VIII. Their production is inhibited by warfarin. Protein C deficiency predisposes to warfarin skin necrosis since protein C and S decrease much more rapidly than clotting factors after warfarin administration leading to an imbalance in pro-to-anticoagulant molecules. Usually heparin is given a few days into warfarin therapy to avoid this initial hypercoagulable state. However in patients with protein C or S deficiency, warfarin skin necrosis can occur up to 10 days after the start of therapy due to very low levels of these anticoagulant proteins. Skin findings on physical exam include petechiae or intial tender red area that progresses to ecchymoses and eventual hemorrhagic bullae. Warfarin should be discontinued as soon as signs of skin necrosis are detected. Educational Objective: Warfarin skin necrosis occurs due to the rapid initial decrease in protein C and S. Protein C deficiency predisposes to severe warfarin skin necrosis. References: Karuppiah SV, Johnstone AJ. Skin necrosis associated with thromboprophylaxis after total knee replacement. Case Rep Orthop. 2014;2014:139218.(Image) Nazarian RM, Van cott EM, Zembowicz A, Duncan LM. Warfarin-induced skin necrosis. J Am Acad Dermatol. 2009;61(2):325-32.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Protein C, WBRKeyword::Warfarin, WBRKeyword::Skin necrosis
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::