Platelet von Willebrand factor.
von Willebrand factor (vWF) circulates in the blood in two distinct compartments. One, plasma vWF, is synthesized and released from endothelial cells; the second, synthesized by megakaryocytes, circulates in platelets primarily stored in the alpha granules. Recent experimental and clinical studies of von Willebrand's disease (vWD) indicate that platelet vWF plays an important role in the bleeding time determination and the degree of clinical bleeding in vWD. Platelet vWF is released from the platelet alpha granules by various agonists and then rebinds to the glycoprotein IIb/IIIa complex. Fibrinogen or monoclonal antibodies against this complex inhibit 60 to 70% of the expression of platelet vWF. Aspirin inhibits 80% of the adenosine diphosphate-induced platelet vWF surface expression, and the platelet vWF surface expression that is not inhibited by aspirin can be almost totally inhibited by disruption of the platelet cytoskeleton. Platelet vWF may, in part, be expressed in the open canalicular system prebound to a receptor. Transfusion studies have shown that correction of the bleeding time in severe vWD requires both plasma and platelet vWF. On the basis of numerous studies, we hypothesize that platelet vWF plays an important role in platelet interaction with the subendothelial surfaces under conditions of high shear stress. After platelet contact, platelet vWF is released, binds to the glycoprotein IIb/IIIa complex, and forms a bridge between the subendothelial surface and the platelet, which initiates and supports platelet spreading. Platelet vWF also acts as an intercellular bridge between platelets and thereby promotes platelet aggregation. This process is important not only in the initial steps of hemostasis but also in the process of thrombosis.
Gralnick
H R
HR
Hematology Service, Clinical Center, National Institutes of Health, Bethesda, Maryland.
Williams
S B
SB
McKeown
L P
LP
Magruder
L
L
Hansmann
K
K
Vail
M
M
Parker
R I
RI
D000818:Animals; D001760:Bleeding Time; D001792:Blood Platelets / Q000378:metabolism* / Q000502:physiology; D001803:Blood Transfusion; D006487:Hemostasis; D006801:Humans; D008954:Models, Biological; D014842:von Willebrand Diseases / Q000097:blood* / Q000503:physiopathology; D014841:von Willebrand Factor / Q000378:metabolism / Q000502:physiology*
D014841:von Willebrand Factor