Direct oral anticoagulant medications in calciphylaxis.

BACKGROUND: Recent studies suggest that calciphylaxis is a thrombotic condition in which arteriolar thrombosis leads to painful skin infarcts and consequent morbidity and mortality. Paradoxically, warfarin is implicated as a risk factor for calciphylaxis. Our objective is to report the use of oral direct thrombin and factor Xa inhibitors (termed direct oral anticoagulants [DOACs]) in patients with calciphylaxis. METHODS: We retrospectively reviewed records of 16 patients with calciphylaxis who received concomitant administration of novel anticoagulants. Patient data, including demographics, comorbidities, other treatments, and adverse events, were abstracted from the health records. RESULTS: Eleven patients (69%) had chronic kidney disease (stage ≥3A), and eight (50%) received dialysis. Apixaban was the most frequently used agent (n = 11 [69%]). Dabigatran (n = 4 [25%]) and rivaroxaban (n = 2 [13%]) were reserved for patients with mild renal impairment (stage ≤2). One clinically relevant but nonmajor bleeding event occurred. There were no major bleeding events. Nine patients (56%) were alive at last follow-up, and five (31%) had complete resolution of their calciphylaxis (mean follow-up, 523 days; range, 26-1884 days). CONCLUSION: DOACs were safe and well tolerated in patients with calciphylaxis, in this initial experience. Several patients had improvement or resolution of calciphylaxis in response to therapy that included DOACs. The degree of renal impairment should guide DOAC choice. Randomized trials are required to determine treatment efficacy.

Survival, Risk Factors, and Effect of Treatment in 101 Patients With Calciphylaxis.

OBJECTIVE: To report on the survival and the associations of treatments upon survival of patients with calciphylaxis seen at a single center. PATIENTS AND METHODS: Using the International Classification of Diseases, Ninth Revision diagnosis code of 275.49 and the keyword "calciphylaxis" in the dismissal narrative, we retrospectively identified 101 patients with calciphylaxis seen at our institution between January 1, 1999, through September 20, 2014, using a predefined, consensus-developed classification scheme. RESULTS: The average age of patients was 60 years: 81 (80.2%) were women; 68 (68.0%) were obese; 19 (18.8%) had stage 0 to 2 chronic kidney disease (CKD), 19 (18.9%) had stage 3 or 4 CKD; 63 (62.4%) had stage 5 or 5D (dialysis) CKD. Seventy-five patients died during follow-up. Six-month survival was 57%. Lack of surgical debridement was associated with insignificantly lower 6-month survival (hazard ratio [HR]=1.99; 95% CI, 0.96-4.15; P=.07) and significantly poorer survival for the entire duration of follow-up (HR=1.98; 95% CI, 1.15-3.41; P=.01), which was most pronounced in stage 5 or 5D CKD (HR=1.91; 95% CI, 1.03-3.56; P=.04). Among patients with stage 5/5D CKD, subtotal parathyroidectomy (performed only in patients with hyperparathyroidism) was associated with better 6-month (HR=0.12; 95% CI, 0.02-0.90; P=.04) and overall survival (HR= 0.37; 95% CI, 0.15-0.87; P=.02). CONCLUSION: Calciphylaxis is associated with a high mortality rate. Significantly effective treatments included surgical debridement and subtotal parathyroidectomy in patients with stage 5/5D CKD with hyperparathyroidism. Treatments with tissue-plasminogen activator, sodium thiosulfate, and hyperbaric oxygen therapy were not associated with higher mortality.

Magnitude and impact of abnormal mineral metabolism in hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Mineral metabolism has emerged as an important predictor of morbidity and mortality in dialysis patients, independent of bone and muscle concerns. Several expert panels have issued management guidelines for mineral metabolism. METHODS: The state of mineral metabolism (serum parathyroid hormone [PTH], phosphorus, calcium, and calcium-phosphorus product) was described for representative samples of patients and facilities from 7 countries (France, Germany, Italy, Japan, Spain, United Kingdom, and United States) participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS I, 1996-2001; DOPPS II, 2002-2004). RESULTS: A relatively modest percentage of patients fell within the guideline range for PTH (21.4% in DOPPS I, 26.2% in DOPPS II), serum phosphorus (40.8%, 44.4%), albumin-corrected serum calcium (40.5%, 42.5%), and calcium-phosphorus product (56.6%, 61.4%). Results were not dramatically different across countries. The majority of patients not within guideline ranges had high serum levels of phosphorus (51.6% in DOPPS I, 46.7% in DOPPS II), calcium (50.1%, 48.6%), and calcium-phosphorus product (43.4%, 38.6%) and low (<150 pg/mL) concentrations of PTH (52.9%, 47.5%). It was rare for patients to fall within recommended ranges for all indicators of mineral metabolism; 23% to 28% fell within guideline for at least 3 measures and only 4.6% to 5.5% of patients were within range for all 4. The risks of all-cause and cardiovascular mortality were directly and independently associated with each of the 4 indicators. CONCLUSION: The DOPPS provides a useful comparison benchmark for the state of mineral metabolism management of patients with kidney disease; it also affirms the association between mineral metabolism and important patient outcomes.