Inhibitors of von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura.

It is shown that inhibitors of vWF-cleaving protease are of low titers in most cases of acquired TTP, and a higher inhibitor titer is associated with a more advanced stage of the disease and may delay the response to plasma exchange.

Abstract

Thrombotic thrombocytopenic purpura (TTP), characterized by platelet thrombi in the arterioles and capillaries, is associated with antibodies that inhibit the activity of von Willebrand factor (vWF)-cleaving protease. Using a modified Bethesda method, we studied the inhibitor titers in patients who participated in the trial conducted by the Canadian Apheresis Group. Among the 41 patients investigated, the inhibitor titers at presentation were 1.4 +/- 1.7 U/mL (range -0.2-6.2 U/mL). Thirty-one patients (76%) had a titer > or = 0.2 U/mL, 8 patients (20%) had a titer > or = 2.0 U/mL but none had a titer > or = 10 U/mL. Among the 33 patients with an inhibitor titer or = 2 U/mL (high titer group), 20 (61%) and 8 (100%) respectively had a platelet count or = 2 U/mL and none responded at the end of the first treatment cycle, while 8 of the 18 patients (44%) with a titer < 2 U/mL responded. This study shows that inhibitors of vWF-cleaving protease are of low titers in most cases of acquired TTP. A higher inhibitor titer is associated with a more advanced stage of the disease and may delay the response to plasma exchange.