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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/17888

Title: Fibrinogen and von Willebrand factor-independent platelet aggregation in vitro and in vivo
Authors: Yang, H
Reheman, A
Chen, P
Zhu, G
Hynes, RO
Freedman, J
Wagner, DD
Ni, H
Department: Laboratory Medicine and Pathobiology
Physiology
St. Michael's Hospital
Keywords: fibrinogen
integrin
intravital microscopy
platelet aggregation
thrombin
thrombosis
Issue Date: Oct-2006
Publisher: Blackwell Publishing
Citation: Yang H et al. Fibrinogen and von Willebrand factor-independent platelet aggregation in vitro and in vivo. J Thromb Haemost. 2006;4(10):2230-7.
Abstract: BACKGROUND: Fibrinogen (Fg) has been considered essential for platelet aggregation. However, we recently demonstrated formation of occlusive thrombi in Fg-deficient mice and in mice doubly deficient for Fg and von Willebrand factor (Fg/VWF(-/-)). METHODS AND RESULTS: Here we studied Fg/VWF-independent platelet aggregation in vitro and found no aggregation in citrated platelet-rich plasma of Fg/VWF(-/-) mice. Surprisingly, in Fg/VWF(-/-) plasma without anticoagulant, adenosine diphosphate induced robust aggregation of Fg/VWF(-/-) platelets but not of beta(3)-integrin-deficient (beta(3) (-/-)) platelets. In addition, beta(3) (-/-) platelets did not significantly incorporate into thrombi in Fg/VWF(-/-) mice. This Fg/VWF-independent aggregation was blocked by thrombin inhibitors (heparin, hirudin, PPACK), and thrombin or thrombin receptor activation peptide (AYPGKF-NH(2)) induced aggregation of gel-filtered Fg/VWF(-/-) platelets in 1 mm Ca(2+) PIPES buffer. Notably, aggregation in PIPES buffer was only 50-60% of that observed in Fg/VWF(-/-) plasma. Consistent with the requirement for thrombin in vitro, hirudin completely inhibited thrombus formation in Fg/VWF(-/-) mice. These data define a novel pathway of platelet aggregation independent of both Fg and VWF. Although this pathway was not detected in the presence of anticoagulants, it was observed under physiological conditions in vivo and in the presence of Ca(2+)in vitro. CONCLUSIONS: beta(3) integrin, thrombin, and Ca(2+) play critical roles in this Fg/VWF-independent aggregation, and both plasma and platelet granule proteins contribute to this process.
URI: http://hdl.handle.net/1807/17888
ISSN: 1538-7933
Appears in Collections:Faculty Publications

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