Late response to cyclosporine in refractory thrombotic thrombocytopenic purpura

Plasma exchange (PEX) with fresh frozen plasma, usually in association with steroid therapy, has been shown to be the first-line treatment of thrombotic thrombocytopenic purpura. It works by removing ultralarge von Willebrand factor (vWF) multimers and inhibitory antibody and by supplying normal protease. For patients with disease refractory to PEX, there is no standardized treatment. Limited and sporadic success with different therapies (vincristine sulfate, prostacyclin, intravenous immunoglobulins, splenectomy) has been described. We report the case of a woman who developed refractory disease after an initial response to PEX and despite a very high number of PEX procedures performed. Low activity (< 5%) of serum vWF-cleaving protease and a low level of protease inhibitor were documented. The patient had a slow but sustained response when oral cyclosporine was administered concomitantly with PEX, which was slowly tapered. The activity of serum vWF-cleaving protease normalized. At relapse, treatment with cyclosporine, added after the failure of steroids and PEX, led to a lasting response. It is possible that in some cases cyclosporine therapy must be of particularly long duration before being considered ineffective.