A 56-year-old man is evaluated for recent onset painful skin lesion which involves his abdominal wall. The lesion started 3 days ago as a small erythematous macule which has gradually increased in size to a large purpuric lesion with bulla formation. He is afebrile and does not recall any trauma. His medical history is significant for atrial fibrillation; he was recently switched from rivaroxaban to warfarin due to the high cost of rivaroxaban.What is the most probable cause of the condition?
Malignancy is a recognized risk factor for venous thromboembolism (VTE), and VTE is the second leading cause of death in cancer patients. Procoagulant molecules expressed both by cancer cells and host tissue contribute to this condition. Low-molecular-weight heparin (LMWH) is the preferred anticoagulant for long-term treatment in patients with cancer. When compared with warfarin, LMWH reduces the rate of recurrent VTE without significant risk of bleeding. Newer anticoagulants such as rivaroxaban have not been adequately tested for cancer-induced VTE yet.Young patients with unprovoked VTE, a history of unexplained VTE, or family history of VTE raise the suspicion of an inherited hypercoagulable disorder. The common inherited hypercoagulable disorders are Factor V Leiden mutation, prothrombin gene mutation, protein S deficiency, protein C deficiency, antithrombin III deficiency, dysfibrinogenemia, and antiphospholipid antibody syndrome. When inherited hypercoagulable disorders are strongly suspected, tests for above mentioned disorders can be ordered. In the event of an acute thrombosis, however, it is not recommended to test for protein C, protein S, and anti-thrombin III since active coagulation can reduce the plasma concentration of these proteins resulting in false-positive result. To avoid confusion, it is recommended to order only Factor V Leiden mutation, prothrombin gene mutation, and antiphospholipid antibody with acute VTE or when patients are on warfarin.Warfarin-induced skin necrosis results from a transient hypercoagulable state. Warfarin initially affects all the vitamin K-dependent clotting proteins (Factors II, VII, IX, X, and proteins C and S). Since Protein C has a short half-life (8-12 hours), the serum protein C concentration drops quickly to 50% of normal in first 24 hours. Since circulating levels of other vitamin K-dependent proteins are still high, this gives rise to a hypercoagulable state which may cause microthrombi in the dermal and subcutaneous vessels, resulting in skin necrosis. The risk is particularly high in case of congenital protein C deficiency; nearly one-third cases of warfarin-induced skin necrosis are associated with congenital protein C deficiency.
Rivaroxaban
Low-molecular-weight heparin
Warfarin
Low dose aspirin (81 mg/d)
Oncology