Activation of the contact pathway of blood coagulation on the circulating microparticles may explain blood plasma coagulation induced by dilution
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Recent studies have shown that the contact activation of blood coagulation can be initiated on the surface of circulating microparticles–particles formed as a result of the activation or apoptosis of blood cells or endothelial cells. In the present work, by means of a mathematical model, we investigated the mechanism of the activation of contact pathway of blood plasma coagulation. The model describes membrane-dependent reactions of the activation of factors XII and XI with account of the presence of blood plasma inhibitors. All reactions were described by ordinary differential equations integrated by an implicit multistep method. The current mathematical model is based on our previous model of factor XII activation on the platelet surface. The initial model is modified by the addition of factor XI, kallikrein, and blood plasma inhibitors. We show that the amidolytic activity of the contact pathway factors associated with the microparticles is proportional to the concentration of microparticles. In previous studies, an increase in the overall solution amidolytic activity after the dilution of plasma was observed. Computational analysis of the contact pathway activation in the diluted plasma shows that the increase in the activation appears from the dilution of blood plasma inhibitors. Thus, a well-known experimental phenomenon of the hypercoagulability of plasma after dilution can be explained by an increased activation of the blood plasma coagulation through the contact pathway on the circulating microparticles. In addition, the computational analysis reveals that a rapid stop of the contact pathway activation on the microparticles observed in the experiments could be explained by the rapid depletion of the free activation surface.
Keywordscirculating microparticles factor XII membrane-dependent reactions
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- 1.Panteleev M.A., Ataullakhanov F.I. 2008. Blood coagulation: Biochemical foundations. Klinicheskaya onkogematologia (Rus.). 1 (1), 50–62.Google Scholar
- 3.Zakharova N.V., Artemenko E.O., Podoplelova N.A., Sveshnikova A.N., Demina I.A., Ataullakhanov F.I., Panteleev M.A. 2015. Platelet surface-associated activation and secretion-mediated inhibition of coagulation Factor XII. PLoS ONE. 10 (2), e0116665. doi 10.1371/journal.pone.0116665CrossRefPubMedPubMedCentralGoogle Scholar
- 4.Lipets E., Vlasova O., Urnova E., Margolin O., Soloveva A., Ostapushchenko O., Andersen J., Ataullakhanov F., Panteleev M. 2014. Circulating contactpathway-activating microparticles together with Factors IXa and XIa Induce spontaneous clotting in plasma of hematology and cardiologic patients. PLoS ONE. 9(1), e87692. doi 10.1371/journal.pone.0087692CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Sinauridze E.I. 2013. Features of hemostasis in hemodilution. Correction of hypercoagulablity after hemodilution by thrombin inhibitors. Doct. Sci. (Biology) Dissertation. Moscow: Hematology Research Center, Ministry of Health, 2013.Google Scholar
- 10.Robert R.M., Decrem D.Y., Rath R.G., Dessy D.C., Feron F.O., Mullier F.M., Devel P.D., Chatelain B.C., Dogné J.M.D., Godfroid E.G. 2011. The tick protein Ir-CPI efficiently delays contact pathway induced thrombin generation and displays in vivo antithrombotic activity. 26th General Meeting of the Belgian Hematological Society, Liège, 2011.Google Scholar
- 21.Jonathan F.T., Fujikawa K. 1987. Primary structure requirements for the binding of human high molecular weight kininogen to plasma prekallikrein and Factor XI. J. Biol. Chem. 262 (24), 11651–11656.Google Scholar