Lupus anticoagulant and combined thrombophilia are risk factors for the development of calciphylaxis among patients with late-stage chronic kidney disease (CKD), according to a new study.

“Prospective screening for these factors may help identify patients with CKD at increased risk for developing calciphylaxis who would benefit from tighter metabolic control and increased screening,” a team led by Daniela Kroshinsky, MD, PhD, of Massachusetts General Hospital in Boston, concluded in a paper published online ahead of print in JAMA Dermatology.

The study compared 38 patients with both calciphylaxis and CKD (case patients) and 114 control patients with CKD matched by age, sex, and race. Among all patients, lupus anticoagulant, protein C deficiency, and combined thrombophilias occurred significantly more frequently in case patients than in controls (48% vs 5%, 50% vs 8%, and 62% vs 31%, respectively). In a subgroup analysis of patients with stage 5 CKD, only lupus anticoagulant and combined thrombophilia were significantly associated with calciphylaxis. These conditions occurred in 53% and 63% of case patients, respectively, compared with 0% and 8% in the control group. In a subgroup analysis of patients not exposed to warfarin, only lupus anticoagulant and protein C deficiency were significantly associated with calciphylaxis. Lupus anticoagulant and protein C deficiency were present in 50% and 46% of case patients, respectively, compared with only 6% and 0% of controls.

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“Overall, these results indicate that [the] presence of lupus anticoagulant is strongly associated with the development of calciphylaxis, even in individuals with severe renal dysfunction who are not using warfarin,” Dr Kroshinsky and her collaborators wrote.

The authors noted that these data “may provide insight for improved prevention and treatment of calciphylaxis, possibly by better managing thombophilic states in appropriate patients.”

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According to the investigators, the current theory about the pathogenesis of calciphylaxis, which also is known as calcific uremic arteriolopathy, is that the disease is caused by caused by cutaneous arteriolar stenosis with subsequent thrombotic occlusion, leading to ischemic necrosis. “Arteriolar calcification is thought to be a result of bone mineral derangements, which are frequently present in patients with severe renal disease.”

In a discussion of study strengths, Dr Kroshinsky’s group said that, to their knowledge, the study is the most comprehensive case-control evaluation of hypercoagulable traits to date with matching by diagnosis with CKD, “a diagnosis within itself that can be associated with alterations in coagulability.”

With regard to study limitations, the investigators pointed out that they matched by diagnosis with CKD rather than by stage 5 CKD or dialysis dependence. “We remedied this by a subgroup analysis of CKD5 case patients and contols.”In addition, controls were not tested for hypercoagulable conditions as frequently as case patients. “Patients with calciphylaxis are more often tested for hypercoagulable states based on current recommendations, whereas case patients were likely tested only if there was clinical suspicion of a prothrombotic state.”


Dobry AS, Ko LN, St. John J, et al. Association between hypercoagulable conditions and calciphylaxis in patients with renal disease: A case-control study. JAMA Dermatol 2017; published online ahead of print. doi: 10.1001/jamadermatol.2017.4920