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Brief Report
January 11, 2017

Warfarin-Associated Nonuremic Calciphylaxis

Author Affiliations
  • 1Department of Dermatology, University of California–San Francisco, San Francisco
  • 2Department of Pathology, University of California–San Francisco, San Francisco
JAMA Dermatol. Published online January 11, 2017. doi:10.1001/jamadermatol.2016.4821
Key Points

Question  Is warfarin-associated calciphylaxis a distinct disease when compared with classic calciphylaxis, and, if so, what are its features?

Findings  In this review of reports of 18 patients with warfarin-associated calciphylaxis, 15 had used warfarin for an average of 32 months prior to calciphylaxis onset, and the most common treatments were substitution of heparin or low-molecular weight heparin for warfarin, intravenous sodium thiosulfate, and hyperbaric oxygen. Survival after hospital discharge was high with 15 cases (83%) reporting full recovery and 3 cases ending in death.

Meaning  Warfarin-associated calciphylaxis is distinct from classic calciphylaxis in pathogenesis, course, and outcome.

Abstract

Importance  Classic calciphylaxis associated with renal failure is a life-threatening disease. Warfarin-associated calciphylaxis without renal injury has been described, but whether it is a subset of classic calciphylaxis or a different entity remains unknown. We describe 1 case of warfarin-associated calciphylaxis, present data from 2 others from our institution, and review all cases of warfarin-associated calciphylaxis available in the literature. Our review indicates that warfarin-associated calciphylaxis is clinically and pathophysiologically distinct from classic calciphylaxis.

Objective  To review warfarin-associated calciphylaxis and determine its relationship to classic calciphylaxis.

Design, Setting, and Participants  We searched MEDLINE and Ovid without language or date restrictions for case reports of calciphylaxis from the inpatient setting using the terms “calciphylaxis and warfarin,” “non-uremic calciphylaxis,” and “nonuremic calciphylaxis.” We defined nonuremic calciphylaxis as a histopathologic diagnosis of calciphylaxis without severe kidney disease (serum creatinine level >3 mg/dL; glomerular filtration rate <15 mL/min; acute kidney injury requiring dialysis; and renal transplantation).

Exposures  Each patient had been exposed to warfarin before the onset of calciphylaxis.

Main Outcomes and Measures  Patient data were abstracted from published reports. Original patient medical records were requested and reviewed when possible.

Results  We identified 18 patients with nonuremic calciphylaxis, 15 from the literature, and 3 from our institution. Patients were predominantly female (15 of 18 [83%]) with ages ranging from 19 to 86 years. Duration of warfarin therapy prior to calciphylaxis onset averaged 32 months. Lesions were usually located below the knees (in 12 of 18 [67%]). No cases reported elevated calcium-phosphate products (0 of 17 [0%]). Calcifications were most often noted in the tunica media (n = 8 [44%]) or in the vessel lumen and tunica intima (n = 7 [39%]). The most common treatments included substitution of heparin or low-molecular weight heparin for warfarin (n = 13 [72%]), intravenous sodium thiosulfate (n = 9 [50%]), and hyperbaric oxygen (n = 3 [17%]). The survival rate on hospital discharge was remarkably high, with 15 cases (83%) reporting full recovery and 3 cases ending in death.

Conclusions and Relevance  Warfarin-associated calciphylaxis is distinct from classic calciphylaxis in pathogenesis, course, and, particularly, outcome. This finding should influence clinical management of the disease and informs targeted treatment of the disease.

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