Acquired von Willebrand Disease in Patients with Chronic Myeloproliferative Disorders

In chronic myeloproliferative disorders(CMPD), thrombohaemorrhagic complications are relatively common, in association with thromocytosis. We studied the multimeric composition of plasma von Willebrand factor(vWf) in CMPD and investigated the possibilities of in vivo or in vitro proteolysis. The relative amount of large multimers in patients with CMPD was significantly decreased in relation to the increment of platelet count compared with normal subjects. This correlated negatively with platelet count(r = -0.625, p < 0.001) but positively for the ristocetin cofactor/von Willebrand factor antigen ratio (r =: 0.392, p < 0.005). All of the patients with primary myelofibrosis who had normal or subnormal platelet counts showed an almost normal multimeric pattern. The vWf abnormalities normalized with decreasing platelet counts after starting chemotherapy or when blast crisis occurred with decreased platelet counts. These vWf abnormalities may have been caused by in vivo proteolysis, because they were not corrected even when blood was obtained in the presence of protease inhibitors. The relative amount of large multimers of vWf did not correlate with plasma concentration of plasmin or elastase which were measured as cc2 plasmin inhibitor-plasmin complex and a, proteinase inhibitor-elastase complex, respectively. So neither plasmin nor elastase appear to be the enzymes responsible for in vivo proteolysis.