WBR0784

Author	[[PageAuthor::Rim Halaby, M.D. [1]]]
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 a painful and enlarging black lesion on the side of her left arm (shown below). She describes that the lesion was initially painful but was only slightly red. As it progressed it became darker, and harder and unbearably painful. She denies any fever, chills, shortness of breath, abdominal pain, or focal neurologic symptoms. Which of the following conditions can be 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. Learning 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. Reference: Nazarian RM, Van cott EM, Zembowicz A, Duncan LM. Warfarin-induced skin necrosis. J Am Acad Dermatol. 2009;61(2):325-32. Educational Objective: References: ]]
Approved	Approved::No
Keyword	WBRKeyword::Protein C, WBRKeyword::warfarin, WBRKeyword::skin necrosis
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::