Effect of prophylactic cyclosporine therapy on ADAMTS13 biomarkers in patients with idiopathic thrombotic thrombocytopenic purpura

Abstract

Several reports have been published regarding the use of cyclosporine (CSA) in the treatment of idiopathic thrombotic thrombocytopenic purpura (TTP). We hypothesized that prophylactic CSA therapy may prevent recurrences in patients with a history of multiple relapses of TTP. Nineteen patients with idiopathic TTP were enrolled on prospective studies at Ohio State University between September 2003 and May 2007. Patients achieving remission remained on CSA therapy for 6 months, allowing us to evaluate the efficacy of CSA as prophylactic therapy. CSA was administered orally at a dose of 2-3 mg/kg in twice a day divided dose in all patients and continued for a total of 6 months. Long-term clinical follow-up with serial analysis of ADAMTS13 biomarkers during and after CSA therapy were performed to evaluate the efficacy of CSA as a prophylactic therapy. 17/19(89%) patients completed 6 months of CSA therapy in a continuous remission. Two patients relapsed during therapy with CSA and seven patients relapsed after discontinuing CSA therapy. Ten patients have maintained a continuous remission a median of 21 months (range, 5-46) after discontinuing CSA. The ADAMTS13 data suggest that CSA resulted in a significant increase in the ADAMTS13 activity during therapy with CSA. 8/9(89%) relapsing patients had severely deficient ADAMTS13 activity (<5%) suggesting this is a significant risk factor for relapse of TTP. These data support the hypothesis that prophylactic CSA improves the ADAMTS13 activity and may be effective at preventing relapses in patients at risk for recurrences of TTP.