title: The changing paradigm of thrombotic thrombocytopenic purpura.
abstract: New discoveries have changed a 20-year-old concept about the mechanism of microvascular thrombosis in thrombotic thrombocytopenic purpura (TTP). The classic model of TTP pathogenesis in which ultra large von Willebrand factor (ULvWF) is proposed to mediate spontaneous platelet aggregation in high sheer stress has evolved into a model in which vWF-platelet aggregates form on stimulated endothelial cell surfaces. The classic model of TTP pathogenesis was based on the proposed pathogenicity of plasma ULvWF in TTP microvascular thrombosis. The current model suggests that platelet binding to endothelial-bound vWF and cleavage of endothelial-bound vWF-platelet aggregates may be most critical in TTP pathogenesis and treatment. A clearer understanding of the mechanism of microvascular thrombosis in TTP will allow better targeted treatment.
authors.affiliation: Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA. Thomas-raife@uiowa.edu
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Raife
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000071120:ADAMTS13 Protein; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008833:Microcirculation / Q000378:metabolism / Q000473:pathology; D008955:Models, Cardiovascular; D010974:Platelet Aggregation; D011697:Purpura, Thrombotic Thrombocytopenic / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D013314:Stress, Mechanical; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human