Title: Key role of glycoprotein Ib/V/IX and von Willebrand factor in platelet activation-dependent fibrin formation at low shear flow
Authors: Cosemans, Judith M. E. M ×
Schols, Saskia E. M
Stefanini, Lucia
de Witt, Susanne
Feijge, Marion A. H
Hamulyak, Karly
Deckmyn, Hans
Bergmeier, Wolfgang
Heemskerk, Johan W. M #
Issue Date: Jan-2011
Publisher: W.B. Saunders
Series Title: Blood vol:117 issue:2 pages:651-660
Abstract: A microscopic method was developed to study the role of platelets in fibrin formation. Perfusion of adhered platelets with plasma under coagulating conditions at a low shear rate (250(-1)) resulted in the assembly of a star-like fibrin network at the platelet surface. The focal fibrin formation on platelets was preceded by rises in cytosolic Ca2+, morphologic changes, and phosphatidylserine exposure. Fibrin formation was slightly affected by alpha(IIb)beta(3) blockage, but it was greatly delayed and reduced by the following: inhibition of thrombin or platelet activation; interference in the binding of von Willebrand factor (VWF) to glycoprotein Ib/V/IX (GpIb-V-IX); plasma or blood from patients with type 1 von Willebrand disease; and plasma from mice deficient in VWF or the extracellular domain of GpIb alpha. In this process, the GpIb-binding A1 domain of VWF was similarly effective as full-length VWF. Prestimulation of platelets enhanced the formation of fibrin, which was abrogated by blockage of phosphatidylserine. Together, these results show that, in the presence of thrombin and low shear flow, VWF-induced activation of GpIb-V-IX triggers platelet procoagulant activity and anchorage of a star-like fibrin network. This process can be relevant in hemostasis and the manifestation of von Willebrand disease. (Blood. 2011;117(2):651-660)
ISSN: 0006-4971
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Chemistry, Campus Kulak Kortrijk
× corresponding author
# (joint) last author

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