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Thromb Haemost 2014; 112(03): 486-494
DOI: 10.1160/TH14-02-0172
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

The effect of fibrin(ogen) on thrombin generation and decay

Romy M. W. Kremers
1   Synapse bv, CARIM, Maastricht University, the Netherlands
,
Rob J. Wagenvoord
1   Synapse bv, CARIM, Maastricht University, the Netherlands
,
H. Coenraad Hemker
1   Synapse bv, CARIM, Maastricht University, the Netherlands
› Author Affiliations
Further Information

Publication History

Received: 25 February 2014

Accepted after major revision: 09 April 2014

Publication Date:
02 December 2017 (online)

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Summary

Defibrination causes a ~30% decrease of thrombin generation (TG) which can be restored by adding native fibrinogen in its original concentration (3 mg/ml). The fibrinogen variant γA/γ′, which binds thrombin with high affinity, is over four times more efficient in this respect than the more common γA/γA form. By using high tissue factor concentrations we accelerated prothrombin conversion so as to obtain a descending part of the TG curve that was governed by thrombin decay only. From that part we calculated the antithrombin (AT)- and α2-macroglobulin- dependent decay constants at a series of concentrations of native, γA/γA and γA/γ′ fibrinogen. We found that the increase of TG in the presence of fibrinogen is primarily due to a dose-dependent decrease of thrombin inactivation by α2-macroglobulin, where the γA/γ′ form is much more active than the γA/γA form. AT-dependent decay is somewhat decreased by γA/γ′ fibrinogen but hardly by the γA/γA form. We assume that binding of thrombin to fibrin(ogen) interferes with its binding to inhibitors. Attenuation of decay only in part explains the stimulating effect of fibrinogen on TG, as fibrinogen stimulates prothrombin conversion, regardless of the fibrinogen variant.

Note: Part of this work was presented at the ISTH meeting in 2013.

Keywords

Fibrinogen - thrombin generation - gamma chain - thrombin decay - prothrombin conversion

 

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