Plasma von Willebrand factor proteolysis in patients with chronic myeloproliferative disorders: no possibility of ex vivo degradation by calcium-dependent proteases.

Patients with chronic myeloproliferative disorders (CMPD) frequently have abnormalities of plasma von Willebrand factor (vWf) multimers. The pathogenesis of this phenomenon is still unknown. In order to evaluate the possibility of ex vivo degradation of vWf during blood processing, we compared vWf antigen, ristocetin cofactor and the multimeric composition of vWf in plasmas obtained in the presence of trisodium citrate with or without calcium-dependent protease inhibitors (leupeptin, N-ethylmaleimide and Na2EDTA). The subjects included 20 patients with CMPD, 11 with other diseases and 8 normal subjects. In patients with CMPD and normal subjects, the values of vWf antigen, ristocetin cofactor, ristocetin cofactor/vWf antigen ratio and the relative amount of large multimers of vWf did not significantly differ from each other in plasma samples with and without protease inhibitors. In other diseases, especially in a patient with disseminated intravascular coagulation, a somewhat higher amount of large multimers were found in plasma with protease inhibitors than without inhibitors. These findings indicate that the ex vivo proteolysis during blood processing is negligible in patients with CMPD, and that the observed abnormalities in vWf is an in vivo phenomenon.