Document Type




Format of Original

7 p.

Publication Date



American Society of Hematology

Source Publication


Source ISSN


Original Item ID

doi: 10.1182/blood-2005-01-0240


Human fibrinogen 1 is homodimeric with respect to its γ chains (`γAA'), whereas fibrinogen 2 molecules each contain one γAA1-411V) and one γ' chain, which differ by containing a unique C-terminal sequence from γ'408 to 427L that binds thrombin and factor XIII. We investigated the structural and functional features of these fibrins and made several observations. First, thrombin-treated fibrinogen 2 produced finer, more branched clot networks than did fibrin 1. These known differences in network structure were attributable to delayed release of fibrinopeptide (FP) A from fibrinogen 2 by thrombin, which in turn was likely caused by allosteric changes at the thrombin catalytic site induced by thrombin exosite 2 binding to the γ' chains. Second, cross-linking of fibrin γ chains was virtually the same for both types of fibrin. Third, the acceleratory effect of fibrin on thrombin-mediated XIII activation was more prominent with fibrin 1 than with fibrin 2, and this was also attributable to allosteric changes at the catalytic site induced by thrombin binding to γ' chains. Fourth, fibrinolysis of fibrin 2 was delayed compared with fibrin 1. Altogether, differences between the structure and function of fibrins 1 and 2 are attributable to the effects of thrombin binding to γ' chains.


Accepted version. Blood, Vol. 106, No. 8 (October 15, 2005): 2730-2736. DOI. © 2005 American Society of Hematology (ASH). Used with permission.

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