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tPA displayed potential as adjuvant therapy for calciphylaxis

Thrombolytic tissue plasminogen activator demonstrated the possibility of being a useful adjunctive treatment for patients with calciphylaxis, according to recent study results.

Researchers at Mayo Clinic, Rochester, Minn., conducted a retrospective chart review of 15 patients with calciphylaxis (median age at diagnosis, 59 years; 11 women) who were treated between 2002 and 2010. The usually fatal thrombotic condition, affecting up to 4% of long-term dialysis patients, results in ischemia, necrosis and infarction of adipose and cutaneous tissue.

Eleven patients (10 women) were obese, and areas of induration and ulceration involved the lower extremities. Three patients also experienced upper extremity involvement, and the torso was affected in four patients. Low-dose, daily infusions of tissue plasminogen activator (tPA) were administered to all patients for a mean of 11 days, along with wound care and management of calcium-phosphate levels. Short-term ulcer healing and long-term survival were primary outcome measures.

No adverse reactions were experienced by six patients; three had minor bleeding, three had major bleeding (gastrointestinal tract, retroperitoneal and subdural hematoma) and six required blood transfusions. No treatment-related complications or hemorrhaging resulted in death.

Of 13 hospitalized patients, 12 had wound improvement, four had complete healing, six had partial healing and two were stabilized. The remaining patient’s wounds worsened. Ten patients died (median time to death, 3.6 months), while median follow-up duration was 36.8 months for patients alive at last follow-up.

Compared with 63 calciphylaxis patients who did not receive tPA (52 died; median time to death, 2.6 months), treated patients had 30% greater survival rate (P=.14).

“We present our protocol using tPA as an adjunctive thrombolytic agent in the treatment of calciphylaxis,” the researchers concluded. “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.

“We recommend long-term continued management of these patients after hospital discharge.”