Abnormal VWF modifies megakaryocytopoiesis: studies of platelets and megakaryocyte cultures from patients with von Willebrand disease type 2B.

摘要: von Willebrand factor (VWF) is an essential mediator of platelet adhesion to the vessel wall, but little known about its role in megakaryocytopoiesis. VWF and receptor, glycoprotein Ibalpha (GPIbalpha), are both expressed during megakaryocyte (MK) maturation. This study was designed evaluate whether enhanced VWF-GPIbalpha interactions typical patients with disease type 2B (VWD2B) modify production. Platelets from 9 VWD2B 7 different gain-of-function mutations were examined by electron microscopy (EM) immunofluorescence labeling. For VWD2B, EM characteristically showed variable numbers structurally abnormal giant platelets, sometimes agglutinates. Cultures MKs controls performed or without purified confirmed a positive influence on production specific inhibition antibody blocking binding GPIbalpha. MK cultures disorganized demarcation membrane system granule distribution. They produced platelets structural abnormalities VWD2B. Confocal examination revealed limited extension pseudopods few large proplatelets. These results confirm that megakaryocytopoiesis modified interactions. data obtained for suggest novel regulatory