Zarnitsina V I, Pokhilko A V, Ataullakhanov F I
National Scientific Center for Hematology, Russian Academy of Medical Sciences, Moscow, Russia.
Thromb Res. 1996 Dec 1;84(5):333-44. doi: 10.1016/s0049-3848(96)00197-1.
This paper continues our study (see Part I) where we modeled the spatio-temporal dynamics of the intrinsic pathway of blood coagulation. Here, we analyzed this model and showed that it describes the threshold behavior of coagulation. When activation is subthreshold (which produces not more than 0.07 nM factor XIa at saturating free calcium concentrations of 2 mM or higher), the concentration of generated thrombin remains below 0.01 nM. At the abovethreshold activation corresponding to factor XIa exceeding 0.07 nM, the concentration of thrombin explosively increases and then abruptly decreases. The peak concentration of thrombin reaches hundreds nM. With respect to free calcium concentration, the system also behaves in a threshold manner. For activation corresponding to 0.3 nM factor XIa, the threshold concentration of free calcium where the outburst of explosive thrombin generation occur is equal to 0.21 mM. The model simulations are in a good agreement with the experimentally recorded kinetics of thrombin generation at different concentrations of free calcium (1). Analysis of the spatial dynamics of coagulation showed that if activation exceeded the threshold level at a certain point, the concentration wave of thrombin arises and propagates at a high speed from the activation zone. The parameters of this wave depends mainly on the efficiency of the feedback loops. The feedback loops through the backbone factors of the intrinsic pathway (autoactivation of factor X or activation of factor XI by thrombin) has a potential for the unlimited propagation of the thrombin wave. With increasing activity of activated protein C (the effect equivalent to that of thrombomodulin), oscillating regimes arise in the model. The first thrombin wave is followed by several secondary running waves. The amplitudes of secondary waves increases to the periphery of the clot consolidating its surface layer.
本文延续了我们的研究（见第一部分），在该研究中我们对血液凝固内源性途径的时空动力学进行了建模。在此，我们分析了该模型，并表明它描述了凝血的阈值行为。当激活处于阈值以下时（在2 mM或更高的饱和游离钙浓度下产生不超过0.07 nM的因子XIa），生成的凝血酶浓度保持在0.01 nM以下。在对应于因子XIa超过0.07 nM的阈值以上激活时，凝血酶浓度呈爆发性增加，然后突然下降。凝血酶的峰值浓度达到数百nM。关于游离钙浓度，该系统也表现出阈值行为。对于对应于0.3 nM因子XIa的激活，发生爆炸性凝血酶生成爆发的游离钙阈值浓度等于0.21 mM。模型模拟与在不同游离钙浓度下实验记录的凝血酶生成动力学结果高度吻合(1)。对凝血空间动力学的分析表明，如果在某一点激活超过阈值水平，凝血酶浓度波就会出现，并从激活区高速传播。该波的参数主要取决于反馈回路的效率。通过内源性途径的主干因子的反馈回路（因子X的自激活或凝血酶对因子XI的激活）具有使凝血酶波无限传播的潜力。随着活化蛋白C活性的增加（其效果等同于血栓调节蛋白），模型中出现振荡状态。第一个凝血酶波之后跟着几个次级行波。次级波的振幅向凝块表面层的周边增加，从而巩固凝块的表面层。
