Affiliations: Department of Bioengineering, Rice University, Houston, TX, USA | Thrombosis Research Section, Department of Medicine, Baylor College of Medicine, Houston, TX, USA | Coulter Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, Atlanta, GA, USA
Note: [] Present address: Department of Chemical Engineering, University of California, Berkeley, CA, USA.
Note: [] Address for correspondence: Larry V. McIntire, PhD, Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0535, USA. Tel.: +1 404 894 5057 or +1 404 727 9827; Fax: +1 404 894 4243; E-mail: larry.mcintire@bme.gatech.edu.
Abstract: Endothelial cells synthesize and secrete von Willebrand factor (VWF) multimers, including unusually large forms (ULVWF), which are usually cleaved into smaller multimers found in normal plasma (P-VWF). Thrombotic thrombocytopenic purpura (TTP) is a microangiopathic disorder characterized by systemic attachment of platelets to inadequately cleaved ULVWF multimers. We have compared ULVWF and P-VWF in their capacity to become immobilized onto surfaces in vitro and their ability to mediate platelet adhesion. We have also used functional assays to directly compare ULVWF forms with purified P-VWF in mediating platelet aggregation in solution. At comparable concentrations, ULVWF is more effectively adsorbed onto glass surfaces than P-VWF and supports increased platelet adhesion. ULVWF is also significantly more potent than P-VWF in mediating both shear-induced platelet aggregation and ristocetin-mediated platelet agglutination.
