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

Rokea A. el-Azhary, MD, PhD; Allison K. Arthur, MD; Mark D. P. Davis, MD; Marian T. McEvoy, MD; Lawrence E. Gibson, MD; Amy L. Weaver, MS; Michael J. Camilleri, MD; David A. Wetter, MD; Roger H. Weenig, MD
JAMA Dermatol. 2013;149(1):63-67. doi:10.1001/2013.jamadermatol.5.
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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.

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Grahic Jump Location

Figure 1. Response to tissue plasminogen activator treatment (patient 11). A, At admission (before treatment). B, One month after treatment. C, Ten months after treatment.

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Grahic Jump Location

Figure 2. Response to tissue plasminogen activator treatment (patient 4). A, At admission (before treatment). B, Ten months after treatment.

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Grahic Jump Location

Figure 3. Survival of patients with calciphylaxis after treatment with tissue plasminogen activator (tPA) (n = 15) or without tPA treatment (n = 62). Differences between the 2 groups were not statistically significant (P = .14).

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