Retrospective Analysis of Tissue Plasminogen Activator as an Adjuvant Treatment for Calciphylaxis

OBJECTIVE: To report our experience with low-dose tissue plasminogen activator in the treatment of calciphylaxis, a rare, usually fatal thrombotic condition that results in ischemia, necrosis, and infarction of adipose and cutaneous tissue. DESIGN: Retrospective chart review. SETTING: Tertiary care academic medical center. PATIENTS: Fifteen patients (4 men and 11 women) with calciphylaxis, treated from January 1, 2002, through December 31, 2010. INTERVENTION: Treatment with tissue plasminogen activator, concomitant wound care, and management of calcium-phosphate status. MAIN OUTCOME MEASURES: Short-term ulcer healing, long-term survival. RESULTS: Patients received daily low-dose infusions of tissue plasminogen activator (mean treatment duration, 11 days). Six patients had no adverse reactions, 3 had minor bleeding, 6 required blood transfusions, and 3 had life-threatening bleeding. No patients died of treatment-related complications. Ten patients died (median time to death, 3.6 months; range, 23 days to 4.2 years). Of the remaining 5 patients, the median duration of follow-up was 36.8 months (range, 70 days to 4.3 years). Patients treated with tissue plasminogen activator had approximately 30% greater survival than controls, but the difference was not significant (P= .14). Our results were limited by the use of concomitant therapies, referral bias for advanced disease, and retrospective case-series design. CONCLUSIONS: Thrombolytic tissue plasminogen activator may be a useful adjunctive treatment in the management of patients with calciphylaxis. However, a multidisciplinary approach that includes aggressive wound care, débridement, thrombolytic therapy, restoration of tissue oxygenation, avoidance of infection, and control of calcium-phosphate homeostasis also is essential.