A MATHEMATICAL-MODEL FOR THE SPATIOTEMPORAL DYNAMICS OF INTRINSIC PATHWAY OF BLOOD-COAGULATION .2. RESULTS

This paper continues our study (see Part I) where we modeled the spati otemporal dynamics of the intrinsic pathway of blood coagulation. Here , we analyzed this model and showed that it describes the threshold be havior of coagulation. When activation is subthreshold (which produces not more than 0.07 nM factor XIa at saturating free calcium concentra tions of 2 mM or higher), the concentration of generated thrombin rema ins below 0.01 nM. At the above threshold activation corresponding to factor XIa exceeding 0.07 nM, the concentration of thrombin explosivel y increases and then abruptly decreases. The peak concentration of thr ombin reaches hundreds nM. With respect to free calcium concentration, the system also behaves in a threshold manner. For activation corresp onding to 0.3 nM factor XIa, the threshold concentration of free calci um where the outburst of explosive thrombin generation occur is equal to 0.21 mM. The model simulations are in a good agreement with the exp erimentally recorded kinetics of thrombin generation at different conc entrations of free calcium (1). Analysis of the spatial dynamics of co agulation showed that if activation exceeded the threshold level at a certain point, the concentration wave of thrombin arises and propagate s at a high speed from the activation zone. The parameters of this wav e depends mainly on the efficiency of the feedback loops. The feedback loops through the backbone factors of the intrinsic pathway (autoacti vation of factor X or activation of factor XI by thrombin) has a poten tial for the unlimited propagation of the thrombin wave. With increasi ng activity of activated protein C (the effect equivalent to that of t hrombomodulin), oscillating regimes arise in the model. The first thro mbin wave is followed by several secondary running waves. The amplitud es of secondary waves increases to the periphery of the clot consolida ting its surface layer. Copyright (C) 1996 Elsevier Science Ltd.