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Original Investigation
February 2018

Association Between Hypercoagulable Conditions and Calciphylaxis in Patients With Renal DiseaseA Case-Control Study

Author Affiliations
  • 1Department of Dermatology, Massachusetts General Hospital, and Harvard Medical School, Boston
  • 2Department of Hematology and Oncology, Boston Medical Center, Boston, Massachusetts
  • 3Department of Nephrology, Massachusetts General Hospital, and Harvard Medical School, Boston
JAMA Dermatol. 2018;154(2):182-187. doi:10.1001/jamadermatol.2017.4920
Key Points

Question  Are there hypercoagulable conditions that are risk factors for development of calciphylaxis?

Findings  In this matched case-control analysis of 152 individuals with chronic kidney disease, lupus anticoagulant, protein C deficiency, and combined thrombophilia were all found to be significantly associated with calciphylaxis development.

Meaning  Clinicians should be aware of these associations in patients with impaired kidney function, and may consider increased screening and appropriate anticoagulation treatment to reduce the risk of calciphylaxis development.

Abstract

Importance  Calciphylaxis is a rare skin disease with high morbidity and mortality that frequently affects patients with renal disease. Hypercoagulable conditions are frequently observed in both patients with calciphylaxis and those with chronic kidney disease (CKD), complicating our understanding of which hypercoagulable conditions are specific to calciphylaxis.

Objective  To identify hypercoagulable conditions that are risk factors for developing calciphylaxis while controlling for CKD.

Design, Setting, and Participants  This was a case-control study, comparing the hypercoagulability status of patients with calciphylaxis and with renal disease with that of a matched control population at 2 large urban academic hospitals in Boston, Massachusetts. Retrospective medical record review of laboratory values was performed to identify patients with hypercoagulable conditions. Case and control patients were further stratified based on both severity of CKD and warfarin. Patients with a dermatologic diagnosis of calciphylaxis between 2006 and 2014 and concomitant CKD were included as cases (n = 38). Three controls (n = 114) per case patient with CKD were included, and were matched by age, sex, and race.

Main Outcomes and Measures  The rate of various hypercoagulable states (ie, antithrombin III [ATIII] deficiency, protein C and S deficiency, factor V Leiden mutation, prothrombin gene mutation [G20210A], elevated factor VIII level, lupus anticoagulant, anti-IgG or IgM cardiolipin antibodies, heparin-induced thrombocytopenia antibodies, and elevation of homocysteine) in patients with calciphylaxis compared with their matched controls.

Results  Of the calciphylaxis cohort, 28 (58%) were female and 18 (55%) were non-Hispanic white. Among all patients, lupus anticoagulant (13 [48%] positive in cases vs 1 [5%] in controls; P = .001), protein C deficiency (9 [50%] vs 1 [8%]; P = .02), and combined thrombophilias (18 [62%] vs 10 [31%]; P = .02) were found to be significantly associated with calciphylaxis. In a subanalysis of patients with stage 5 CKD, only lupus anticoagulant (12 [53%] vs 9 [0%]; P = .01) and combined thrombophilia (15 [63%] vs 1 [8%]; P = .004) remained significantly associated with calciphylaxis. In a separate subanalysis of warfarin-unexposed patients, only lupus anticoagulant (7 [50%] vs 1 [6%]; P = .01) and protein C deficiency (5 [46%] vs 10 [0%]; P = .04) remained significantly associated with calciphylaxis.

Conclusions and Relevance  Presence of lupus anticoagulant and combined thrombophilias are risk factors for the development of calciphylaxis in patients with late-stage renal disease. Clinicians should be aware of these associations in patients with impaired kidney function and may consider increased screening and appropriate anticoagulation treatment to reduce the risk of calciphylaxis development.

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