Decreased von Willebrand factor protease activity associated with thrombocytopenic disorders

Recent studies investigating thrombotic thrombocytopenic purpura (TTP) have implicated abnormal plasma von Willebrand factor (vWF)-cleaving metallopro tease activity in this disorder. It has been proposed that a metalloproteas e cleaves unusually large (UL) multimers of vWF, which enter the circulatio n from the endothelium. Abnormal metalloprotease activity could result in U LvWF, which could participate in TTR However, the diagnostic specificity of abnormalities in the plasma metalloprotease activity has not been establis hed. A prospective study of vWF protease activity was performed using sampl es from 20 healthy controls, 20 patients with acute TTP, 20 patients with i mmune idiopathic thrombocytopenic purpura (ITP), 10 patients with dissemina ted intravascular thrombocytopenia (DIC), 10 patients with systemic lupus e rythematosus (SLE,) and 5 thrombocytopenic patients with leukemia. Studies were performed blinded to the diagnosis. Samples from hospitalized patients with normal platelet counts were also tested. The vWF digests and multimer analysis were done using previously described methods. Six laboratory pers onnel independently scored each of the multimer gels. Reduced protease acti vity was observed in 9 of 20 patients with TTR Reduced activity was also ob served in 6 of 20 patients with ITP, 6 of 10 patients with DIC, 5 of 10 pat ients with SLE, I of 5 patients with leukemia, 2 of 20 healthy controls, an d 3 of 25 hospitalized patients. This study indicates that abnormalities of vWF protease activity are not restricted to patients with the diagnosis of TTP.