Abstract
Coagulopathy from warfarin administration and abnormal protein C or S function have been implicated in the development of CUA. Warfarin can lead to a reduction of plasma protein C levels. The use of warfarin prior to the onset of calciphylaxis
was a significant risk factor in some studies (7,38), while not in others (9). Calciphylaxis has reported to occur in patients with functional protein C or S deficiency or
antiphospholipid antibodies (12,62,63). The hypercoagulable or prothrombotic state
from warfarin therapy, protein C or S deficiency, or antiphospholipid may contribute
to skin necrosis via small vessel thrombosis in CUA (62). However, most patients on
dialysis are successfully anticoagulated with heparin or warfarin without developing
CUA (64), and normal functional protein C activity has been recorded in the majority
of cases (25,26). Local trauma, such as subcutaneous injections of insulin (24), and
iron dextran (65) are other possible precipitants of calciphylaxis (66). Additional triggering factors, listed in Table 3, such as protein malnutrition (12,24), albumin infusion (15), corticosteroids (67), chemotherapy, and immunosuppressants (16,18,36),
have also been suggested. Despite their inconsistent and unclear association with
CUA, all the above factors may act as the challenging agents used by Selye in his
animal models; they cause cellular injury in an environment that has already been
‘‘sensitized’’ to calcification.