SKIN NECROSIS ASSOCIATED WITH ACQUIRED PROTEIN-C DEFICIENCY IN PATIENTS WITH RENAL-FAILURE AND CALCIPHYLAXIS

purpose: To determine if the natural anticoagulant protein C plays a role in the pathogenesis of systemic calciphylaxis, a syndrome characterized by extensive vascular and soft tissue calcification and skin necrosis, which is similar to that seen in warfarin-induced skin necrosis. patients and methods: The study population included five patients with end-stage renal disease and systemic calciphylaxis undergoing hemodialysis, 12 patients without evidence of calciphylaxis undergoing dialysis, eight patients with nephrotic syndrome, and eight normal healthy volunteers. Protein C antigen levels were measured by rocket immunoelectrophoresis, and functional activity was quantitated by a chromogenic assay and an anticoagulant assay utilizing the venom of Agkistrodon contortrix. results: Skin biopsy specimens of involved areas in three patients showed thrombotic occlusion of venules identical to that seen in warfarin-induced skin necrosis. Protein C antigen levels were normal in all groups. However, protein C activity was significantly reduced as measured by chromogenic (p<0.01) or anticoagulant assays (p<0.01) in patients with calciphylaxis compared with the other three groups. conclusion: These findings suggest that hypercoagulability due to functional protein C deficiency may contribute to thrombosis, resulting in skin necrosis and digital gangrene in systemic calciphylaxis. © 1990.