Simulation of the extrinsic pathway of the plasmatic clotting system

Activation of the extrinsic plasmatic clotting system was simulated in a computerized analysis. The results were compared with previously described experimental investigations in plasma with isolated clotting factor deficiency, which led to the conclusion that the sequence of patterns for constants of a function describing the extinction curves is related to the sequence of steps of clotting factor activation. The kinetics of activation resulting in extinction curves that correspond to the curves obtained from experimental measurements are described by sets of stiff coupled linear differential equations. The set of functions can be numerically solved without further approximations. As for experimental extinction curves the simulated extinction curves are characterized by an empirical function with three constants. The distribution patterns for the constants are qualitatively similar to experimental patterns, if the following assumptions are made: (1) feedback reaction occurs from factor IIa via factor V, and (2) the conversion of factor II by factor Xa occurs at a rate considerably slower than the conversion of factor II by the prothrombinase complex. A feedback reaction by factor Xa via factor VII accelerates the formation of factor X, although the distribution pattern remains similar to the distribution pattern for a mechanism without the feedback reaction, provided that the initial activation of factor X occurs at a fast rate. A feedback reaction by factor Xa via factor V in addition to the feedback reaction by factor IIa via factor V accelerates the activation, while the pattern distribution remains unchanged. The simultaneous inhibition of factor Xa and factor IIa by antithrombin III does not change the pattern distribution, while the formation of activated factor II is decelerated.