Ukr.Biochem.J. 2013; Volume 85, Issue 6, Nov-Dec, pp. 94-105

doi: http://dx.doi.org/10.15407/ubj85.06.094

A novel mechanism controlling the growth of hemostatic thrombi

11.11.2015   Uncategorized   No comments

V. K. Lishko, I. S. Yermolenko, N. P. Podolnikova, T. P. Ugarova

School of Life Sciences, Arizona State University, Tempe, AZ USA

Current knowledge of the mechanisms of blood coagulation does not provide an answer to one pivotal question: why is, in contrast to a pathological thrombus, the growth of normal hemostatic clot after blood vessel injury suddenly terminated? In the present paper, we summarize the results of our investigations that give an answer to this question. We show that the surface of fibrin clot in the circulation is coated with a thin metastable layer of fibrinogen which is not able to support adhesion of blood cells. Consequently, platelets and leukocytes, the cells expressing adhesive integrins, are incapable of consolidating­ their grip on the surface and washed away by blood flow, thereby preventing the thrombus propagation. The cells that escaped this fibrinogen shield and reached a solid fibrin matrix use an additional mechanism – the ability to activate plasminogen bound either to the surface of cells or to fibrin. Plasmin formed at the interface between the cells and the clot locally degrades fibrin resulting in the fragmentation of the surface rendering it unstable, non-adhesive and therefore non-thrombogenic. Thus, the growth of hemostatic thrombus is halted by two mechanisms, fibrinogen- and plasminogen-dependent, both of which are based on the same principle – the generation of the mechanically unstable, non-adhesive surface.

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