Models of blood coagulation

We have used three models to study the process of tissue factor-initiated blood coagulation. These are: synthetic 'plasma' mixtures prepared with the proteins and membranes involved in the reaction and its regulation; mathematical models based on the reaction kinetics, binding constants and stoichiometries of individual procoagulant and inhibitor reactions, and contact pathway-inhibited coagulation of minimally altered whole blood in vitro. In all of these models, the procoagulant process may be divided into two phases: an initiation phase and a propagation phase. The initiation phase is characterized by the appearance of thrombin and other coagulation enzymes, and the activation of pro-cofactors V and VIII. The propagation phase is characterized by explosive and extensive prothrombin activation. During normal blood coagulation, the bulk of thrombin generation occurs after clot formation, while most release of fibrinopeptide A is observed just at the conclusion of the initiation phase. In the case of haemophilia A and B, the initiation phase is slightly extended, while thrombin generation during the propagation phase is significantly suppressed. The clot time, as well as fibrinopeptide release, is delayed in these patients. Data obtained in our laboratory, employing the above models, indicate that they are efficient tools for blood coagulation studies