Warfarin-associated calciphylaxis in a patient with normal renal function

A 61-year-old woman with a history of diabetes and hypothyroidism presented with extensive necrotic skin lesions that had started as tender subcutaneous nodules in her thighs, buttocks, distal legs, and abdominal wall 5 months prior to presentation and 15 months after having been started on warfarin for pulmonary hypertension. The nodules had become confluent and ulcerated, with black eschar formation and intermittent pus drainage (Panel A). Warfarin-induced skin necrosis had initially been suspected and warfarin was discontinued 3 months prior to presentation; however, the ulcers continued to worsen over this period. She later developed necrotic lesions in her fingertips, and hand radiographs revealed extensive arterial calcification (Panel B).

Panel A Panel B

A deep excisional biopsy of a subcutaneous nodule in the abdominal wall showed extensive fat necrosis and marked calcium deposition in the walls of multiple arterioles (Panel C). Vessel lumen were narrowed or occluded by endothelial cell proliferation and fibrin thrombi. No vasculitic changes or extravascular calcium deposition were present. Laboratory investigation revealed normal levels of serum creatinine (estimated glomerular filtration rate ≥60 mL/min), calcium, phosphorus, parathyroid hormone, and vitamin D. An extensive thrombophilia work-up was negative.

Panel C

A diagnosis of calciphylaxis was made. Calciphylaxis is an uncommon condition characterized by calcification of small arterioles that can lead to luminal obstruction and skin ischemia with ulcerations and necrosis. This case is unusual in that calciphylaxis usually occurs in the setting of end-stage renal disease and hyperparathyroidism. It can be triggered or worsened by vitamin K antagonist therapy, possibly due to a decrease in the vitamin K-dependent gamma-carboxylation of matrix Gla-protein, a protein involved in the calcium efflux from the vascular wall, leading to extensive vascular calcification. ¹

The patient was treated with low molecular weight heparin, bisphosphonates, antibiotics, and diligent wound care. Her thigh and buttock wounds healed 12 months later (Panel D).

Panel D

‘Images in vascular medicine’ is a regular feature of Vascular Medicine. Readers may submit original, unpublished images related to clinical vascular medicine. Submissions may be sent to: Heather L Gornik, Editor in Chief, Vascular Medicine, via the web-based submission system at http://mc.manuscriptcentral.com/vascular-medicine.