Skin necrosis associated with acquired protein C deficiency in patients with renal failure and calciphylaxis.
OBJECTIVE
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.


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 less than 0.01) or anticoagulant assays (p less than 0.01) in patients with calciphylaxis compared with the other three groups.


CONCLUSIONS
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.
Mehta
R L
RL
Department of Medicine, University of Rochester School of Medicine and Dentistry, New York.
Scott
G
G
Sloand
J A
JA
Francis
C W
CW
D000328:Adult; D000368:Aged; D002114:Calcinosis / Q000378:metabolism*; D002115:Calciphylaxis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007122:Immunoelectrophoresis / Q000379:methods; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D009404:Nephrotic Syndrome / Q000378:metabolism; D011486:Protein C / Q000032:analysis; D020151:Protein C Deficiency; D006435:Renal Dialysis; D012867:Skin / Q000473:pathology*
D011486:Protein C