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Von Willebrand disease (VWD) is among the most common inherited bleeding disorders. Interestingly, acquired von Willebrand syndrome (AVWS) is diagnosed much less frequently, but can be identified in association with a substantial number of medical conditions and diseases, including lymphoproliferative (48%), cardiovascular (21%), myeloproliferative (15%), other neoplastic (5%), and autoimmune disorders (2%). Most recently, AVWS has been diagnosed in patients with aortic valve stenosis (AS, 79%) and continuous-flow left ventricular assist devices (LVAD, up to 100%).1) Immune mechanisms mediated reduction of VWF activityAutoantibodies to VWF have been identified in association with monoclonal gammopathies, lymphoid, neoplasms, and autoimmune diseases. Some autoantibodies have higher affinity to high molecular weight-VWF multimers (HMW-VWFMs); clearance of HMW-VWFMs leads to bleeding.2) Non-immune mechanisms induced reduction of VWF activityOne of the mechanisms is VWF adsorption onto malignant cells and paraproteins (i.e., as in multiple myeloma) and thereby removed from the blood circulation. VWF-linked proteolysis can be induced by shear stress. According to high levels of shear stress in AS and LVAD, HM-VWFMs are more susceptible to cleavage by ADAMTS13. We will find a large number of AVWS cases related to cardiovascular diseases.

von Willebrand disease is a genetic hemostatic disorder that is caused by the qualitative or quantitative dysfunction of the von Willebrand factor (VWF), which is involved in hemostasis. A similar dysfunction sometimes develops without mutations, known as acquired von Willebrand syndrome (AVWS) 1) , which has been associated with lymphoproliferative diseases, myeloproliferative diseases, malignant tumors, and hypothyroidism. Recently, it was remarkably noted that cardiovascular diseases with high intravascular shear stress could cause AVWS 2-4) . The incidence of cardiovascular disease-associated AVWS is exceptionally high, and we may encounter such patients in daily clinical settings. Further, special consideration is necessary for the treatment of bleeding since the cause of AVWS is based on the accelerated degradation of VWF.

Thrombotic thrombocytopenic purpura (TTP) is an uncommon disorder. Several hypotheses have been reported up to now but, the pathogenesis is not yet clear. On the other hand, von Willebrand factor (vWf) plays a role in platelet agglutination in initial hemostasis. Moake and other investigators suggested plasma vWf abnormalities. In this paper, we analysed vWf antigen, ristocetin cofactor (RCof) and multimeric composition of vWf in 16 patients with TTP. It was found that vWf antigen and RCof ranged from very low to very high levels, but RCof was lower than vWf antigen except in two cases. Decrease of large multimer of vWf was seen in 11 patients (69%). These abnormalities were corrected at remission by therapy.

A Case of delivery in a 23-year-old woman after a prophylactic infusion of DDAVP is described. She had a life-long history of easy bruising and frequent epistaxis, with the diagnosis of vWD being made when she was 14 years old. A hemostatic examination showed a prolonged bleeding time, a moderate reduction in the factor VIII level (VIII: C) and von Willebrand Factor Antigen (vWF: Ag), decreased platelet aggregation by ristocetin, and depletion of platelet retention. In April, 1988, in the 34th week of pregnancy, she was admitted to our clinic in order to avoid abnormal bleeding during labor. On admission, the level of factor VIII, ristocetin aggregation, and platelet retention were normal, but the bleeding time remained prolonged. The diagnosis of vWD type I was made on the normal multimeric structure. The DDAVP infusion test revealed a shortening of the bleeding time and an increase in the vWF: Ag. In the 41st week of pregnancy, labor was induced, accompanied by infusion of DDAVP, she gave birth to an infant without any abnormal bleeding. Since conventional treatments with human plasma derivatives may cause complicating viral infections, we propose the infusion of DDAVP is one of the treatments to prevent the abnormal bleeding of the patient with vWD during labor.