Mathematical modeling of material-induced blood plasma coagulation

Contact activation of the intrinsic pathway of the blood coagulation cascade is initiated when a procoagulant material interacts with coagulation factor XII, (FXII) yielding a proteolytic enzyme FXIIa. Procoagulant surface properties are thought to play an important role in activation. To study the mechanism of interaction between procoagulant materials and blood plasma, a mathematical model that is similar in form and in derivation to Michaelis-Menten enzyme kinetics was developed in order to yield tractable relationships between dose (surface area and energy) and response (coagulation time (CT)). The application of this model to experimental data suggests that CT is dependent on the FXIIa concentration and that the amount of FXIIa generated can be analyzed using a model that is linearly dependent on contact time. It is concluded from these experiments and modeling analysis that the primary mechanism for activation of coagulation involves autoactivation of FXII by the procoagulant surface or kallikrein-mediated reciprocal activation of FXII. FXIIa-induced self-amplification of FXII is insignificant. (c) 2005 Elsevier Ltd. All rights reserved.