A 50-year-old woman comes to the emergency department due to a large, painful skin lesion. She does not remember sustaining any trauma. She was recently diagnosed with atrial fibrillation and started on treatment with warfarin. The patient noticed the lesion about a day and a half after starting the medication. Temperature is 36.7 C (98 F), blood pressure is 130/82 mm Hg, and pulse is 88/min and irregularly irregular. Physical examination findings are shown in the image below. The remainder of the skin examination is normal. Which of the following is the most likely cause of this patient's skin lesion?

Question

A 50-year-old woman comes to the emergency department due to a large, painful skin lesion.  She does not remember sustaining any trauma.  She was recently diagnosed with atrial fibrillation and started on treatment with warfarin.  The patient noticed the lesion about a day and a half after starting the medication.  Temperature is 36.7 C (98 F), blood pressure is 130/82 mm Hg, and pulse is 88/min and irregularly irregular.  Physical examination findings are shown in the image below.  The remainder of the skin examination is normal.  Which of the following is the most likely cause of this patient's skin lesion?

Quizplus · Accepted Answer

This patient was started on warfarin to prevent thromboembolism secondary to atrial fibrillation. The sharply demarcated purpuric lesion likely represents warfarin-induced skin necrosis, a rare complication that results from an excessive decrease in protein C activity; patients with underlying protein C deficiency are at increased risk. Protein C and S are innate anticoagulants that are vitamin K dependent, as are procoagulant factors II, VII, IX, and X. Warfarin inhibits epoxide reductase (responsible for regenerating vitamin K), which leads to decreased levels of these proteins. Factor VII and protein C are depleted first due to their shorter half-life. The early loss of protein C activity relative to procoagulant factor activity leads to a transient hypercoagulable state that persists until the other procoagulant factors are sufficiently inhibited. In patients with protein C deficiency, this procoagulant state is exaggerated, promoting microvasculature occlusion and hemorrhagic skin necrosis. Underlying protein S deficiency also increases the risk of warfarin-induced skin necrosis, though not to the same extent. Treatment of warfarin-induced skin necrosis includes discontinuing warfarin and administering fresh frozen plasma or protein C concentrate. The condition may be prevented by the coadministration of heparin during the first several days of warfarin therapy. (Choice A) Allergic drug reactions are immune-mediated hypersensitivity reactions that can have variable cutaneous findings ranging from diffuse erythematous eruptions to extensive blistering and exfoliation (eg, Stevens-Johnson syndrome/toxic epidermal necrolysis); this patient's recent warfarin use and localized skin findings are more suggestive of warfarin-induced skin necrosis. (Choice B) Antithrombin deficiency can be inherited (autosomal dominant) or acquired (eg, cirrhosis, nephrotic syndrome) and presents with venous thromboembolism (eg, deep vein thrombosis, pulmonary embolism) and resistance to heparin. Warfarin does not affect antithrombin activity. (Choice C) Heparin-induced thrombocytopenia is an autoimmune phenomenon that causes arterial and venous thrombosis. It can produce skin findings similar to this patient's but would generally be associated with thrombocytopenia and recent heparin use. (Choice E) Vitamin K deficiency most often occurs in patients with fat malabsorption or those taking broad-spectrum antibiotics. The deficiency increases the inhibitory effect of warfarin on all vitamin K-dependent proteins (both anticoagulant and procoagulant), so it does not alter the relative coagulability balance to encourage warfarin-induced skin necrosis. Education objective: Patients started on warfarin develop a transient hypercoagulable state due to the short half-life of protein C. This hypercoagulability is further exaggerated by preexisting protein C deficiency and can result in thrombotic occlusion of the microvasculature with skin necrosis. __________ References: Warfarin-induced skin necrosis. (http://www.ncbi.nlm.nih.gov/pubmed/25673894)

A 50-Year-Old Woman Comes to the Emergency Department Due to a Large