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Prepublished online as a Blood First Edition Paper on July 12, 2002; DOI 10.1182/blood-2002-02-0508.
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Blood, 15 November 2002, Vol. 100, No. 10, pp. 3604-3610
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Distinct and concerted functions of von Willebrand factor and
fibrinogen in mural thrombus growth under high shear
flow
Hideto Matsui,
Mitsuhiko Sugimoto,
Tomohiro Mizuno,
Shizuko Tsuji,
Shigeki Miyata,
Michio Matsuda, and
Akira Yoshioka
From the Department of Pediatrics, Nara Medical
University, Kashihara, Nara, Japan; the Division of
Transfusion Medicine, National Cardiovascular Center, Suita, Osaka,
Japan; and the Center for Molecular Medicine, Jichi
Medical School, Kawachi-gun, Tochigi, Japan.
Using a perfusion chamber and confocal laser scanning microscopy,
we analyzed the interplay of von Willebrand factor (VWF) and fibrinogen
during thrombus growth on a collagen surface under physiologic high
shear rate conditions. During initial thrombogenesis, platelet thrombi
were constructed totally by VWF, not by fibrinogen. Fibrinogen
accumulated predominantly inside the growing thrombi as a function of
time, whereas the thrombus surfaces directly exposed to flow were
occupied constantly by VWF throughout the observation period. In
perfusion of afibrinogenemia (AF) blood lacking both plasma and
platelet fibrinogen, the final height and volume of thrombi were
significantly reduced compared with controls, albeit the area of
surface coverage was normal. The impaired thrombus growth in AF was
only partially corrected by the addition of purified fibrinogen to AF
blood, whereas the addition of purified VWF to blood of severe von
Willebrand disease (VWD) completely normalized the defective thrombus
growth in this disease. Thus, the initial 2-dimensional thrombus
expansion involves only VWF, whereas the time-dependent accumulation of
fibrinogen, released from activated platelets, acts as a core adhesive
ligand, increasing thrombus strength and height and resulting in
3-dimensional thrombus development against rapid blood flow.
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