Predicting response to plasma exchange in patients with thrombotic thrombocytopenic purpura with measurement of vWF-cleaving protease activity. Mori Y, Wada H, Gabazza EC, Minami N, Nobori T, Shiku H, Yagi H, Ishizashi H, Matsumoto M, Fujimura Y. Transfusion 2002;42(5):572-580.

Severe deficiency of von Willebrand factor-cleaving protease (vWF-CPase) activity was recently found in patients with thrombotic thrombocytopenic purpura (TTP). Although the survival of patients with TTP has been dramatically improved with plasma exchange (PE), there are still many patients who are refractory to PE and immunosuppressive therapy. The activities of vWF-CPase and its inhibitor were measured in 27 patients with nonfamilial TTP and hemolytic-uremic syndrome (HUS) to examine the relationship between the clinical variables and vWF-CPase activity. The subjects were categorized in three groups according to the clinical and laboratory criteria. There were 18 patients with TTP, 7 with HUS and 2 with drug-induced HUS (who had colon cancer). All TTP cases were of the nonfamilial form of TTP. The mean age of the TTP patients was 48 years and that of HUS patients was 52 years. Eight of nine patients with HUS had more than 40% of vWF-CPase activity in the acute phase, whereas one had 28% of the normal level at the acute phase. Ten of 12 TTP patients with a good outcome had a severe deficiency of vWF-CPase activity and its inhibitor, whereas four of six patients with a poor outcome had a moderate deficiency of vWF-CPase activity along with a lack of the inhibitor. PE produced normalization of the vWF-CPase activity and neutralization of the inhibitor in TTP patients with a good outcome; however, some TTP patients with vWF-CPase inhibitor relapsed and required immunosuppressive therapy. The response to the combination therapy with PE and immunosuppressive treatment was poor in TTP patients without a severe deficiency of vWF-CPase activity. Three of the six TTP patients with a poor outcome died during the first acute episode before sufficient PE or steroid therapy was provided. The authors conclude that assays of vWF-CPase activity and its inhibitor may be useful for predicting the response to therapy and the outcome of patients with TTP. In some patients, nonfamilial TTP with a poor prognosis may not be caused by a constitutional or acquired deficiency of vWF-CPase with its inhibitor. Although PE and immunosuppressive therapy are effective in patients with nonfamilial TTP and a vWF-CPase inhibitor, other therapeutic modalities may be needed for nonfamilial TTP with unknown etiology.