The Effects of Platelets on Activation Threshold of the Coagulation System

Abstract number: P1803

Khanin MA, Druzhinin AV

Activation threshold of the coagulation system has been established using mathematical modeling technique (Khanin, Semenov, JTB, 1989, Biofiz, 1991) and confirmed biochemically (Ataullakhanov, 1994). The purpose of this study is to examine the effect of activated platelets on activation threshold of the coagulation system using mathematical modeling technique. The model is a set of nonlinear coupled ODEs. A scheme of the biochemical reactions involved includes known enzymatic and second-order reactions as well as inhibition. To determine the activation threshold, the dynamics of thrombin generation is studied by computer simulation. The threshold is defined as a minimal surface tissue factor (TF) concentration at which the baseline state of the coagulation system loses its stability. Two different states of the coagulation system are considered. In one of these states, platelets are not yet activated and hence kinetic constants for biochemical reactions are minimal. In the absence of activated platelets, coagulation biochemical reactions occur mainly in volume, i.e. without the participation of phospholipids and platelet receptors. If platelets are not yet activated, then enzymatic and second-order reactions occur mainly in plasma. The baseline concentrations of other activated clotting factors are also determined. In the other active state, platelets are activated in the injury zone and hence Kcat are markedly increased and Km decreased. In this case the activation threshold is significantly decreased. Thus, the coagulation is triggered only in the present of activated platelets.