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Prepublished online as a Blood First Edition Paper on July 12, 2002; DOI 10.1182/blood-2002-02-0508.
Submitted February 15, 2002
Accepted July 2, 2002
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
Division of Transfusion Medicine, National Cardiovascular Center, Suita, Osaka, Japan
* Corresponding author; email: sugi-ped{at}naramed-u.ac.jp.
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 totally constructed by vWF, not by fibrinogen. Fibrinogen accumulated predominantly inside the growing thrombi as a function of time, while the thrombus surfaces directly exposed to flow were constantly occupied 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 as compared to 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 two-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 three-dimensional thrombus development against rapid blood flow.
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