High titers of inhibitors of von Willebrand factor-cleaving metalloproteinase in a fatal case of acute thrombotic thrombocytopenic purpura.

Acute thrombotic thrombocytopenic purpura is a disease with diffuse platelet thrombi in the microcirculation. Despite plasma exchange therapy, approximately 20 percent of the patients succumb to the disease. A significant number of the survivors suffer one or more relapses. This study investigated the activity of von Willebrand factor-cleaving metalloproteinase and the titers of IgG inhibitors to the proteinase in serial plasma samples from a patient who died during a relapse of the disease despite continued plasma exchanges. A deficiency in the von Willebrand factor-cleaving metalloproteinase activity, due to inhibitory IgG, was detected at presentation. After initiation of plasma exchange, a transient increase in proteinase activity coincided with clinical remission. When thrombocytopenia relapsed, the activity of the proteinase also declined to undetectable levels. Toward the end of her course, proteinase levels raised by plasma exchange were not sustained because the proteinase activity was quickly neutralized by rising titers of inhibitors. High titers of inhibitors of von Willebrand factor-cleaving metalloproteinase cause refractoriness to standard plasma therapy. These findings suggest that intensive plasma exchanges and measures that suppress antibody titers may prevent death and promote remission in refractory cases.