Review Question - QID 109682

This patient who developed necrotic skin lesions after being bridged to warfarin following a provoked deep venous thrombosis most likely has protein C/S deficiency. These proteins cooperate to inhibit factors V and VIII.

Warfarin is a commonly used oral anticoagulant that is used to provide prophylaxis against deep venous thrombosis and pulmonary embolism in patients. One known complication of warfarin is warfarin skin necrosis, which is caused by microvascular thrombi in the early stages of taking warfarin. This thrombotic event results because the levels of proteins C and S decrease first before the clotting factors decrease, meaning that the patient is transiently hypercoagulable. Patients with an existing genetic defect in factors C or S are more predisposed to having this complication.

Incorrect Answers:
Answer 1: Factor II only would be inhibited by direct thrombin inhibitors such as dabigatran; however, these drugs do not cause skin necrosis.

Answer 2: Factor II and X would be affected by a mutation to thrombomodulin; however, this mutation is not known to be directly associated with warfarin skin necrosis.

Answer 3: Factors II, VII, IX, and X are inhibited by warfarin, which was likely administered to this patient; however, it is not the underlying reason that the patient was predisposed to warfarin skin necrosis.

Answer 4: Factor V only would be affected by the factor V Leiden mutation; however, this mutation is not known to be directly associated with warfarin skin necrosis.

Bullet Summary:
Warfarin skin necrosis is caused by a transient hypercoagulable state where the levels of proteins C and S decrease faster than clotting factors.