title: Warfarin-Associated Nonuremic Calciphylaxis.
abstract: 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.
  
  
  
  To review warfarin-associated calciphylaxis and determine its relationship to classic calciphylaxis.
  
  
  
  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).
  
  
  
  Each patient had been exposed to warfarin before the onset of calciphylaxis.
  
  
  
  Patient data were abstracted from published reports. Original patient medical records were requested and reviewed when possible.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Dermatology, University of California-San Francisco, San Francisco.
authors.forename: Wesley Yung-Hsu
authors.initials: WY
authors.lastname: Yu
authors.affiliation: Department of Dermatology, University of California-San Francisco, San Francisco.
authors.forename: Tina
authors.initials: T
authors.lastname: Bhutani
authors.affiliation: Department of Dermatology, University of California-San Francisco, San Francisco.
authors.forename: Rachel
authors.initials: R
authors.lastname: Kornik
authors.affiliation: Department of Dermatology, University of California-San Francisco, San Francisco2Department of Pathology, University of California-San Francisco, San Francisco.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Pincus
authors.affiliation: Department of Dermatology, University of California-San Francisco, San Francisco.
authors.forename: Theodora
authors.initials: T
authors.lastname: Mauro
authors.affiliation: Department of Dermatology, University of California-San Francisco, San Francisco.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Rosenblum
authors.affiliation: Department of Dermatology, University of California-San Francisco, San Francisco.
authors.forename: Lindy P
authors.initials: LP
authors.lastname: Fox
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects*; D002115:Calciphylaxis / Q000139:chemically induced* / Q000150:complications / Q000175:diagnosis; D005260:Female; D006801:Humans; D007871:Leg Ulcer / Q000209:etiology; D054068:Livedo Reticularis / Q000209:etiology; D011693:Purpura / Q000209:etiology; D014859:Warfarin / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D014859:Warfarin