Thrombin generation in clotting factor deficiency: mathematical model

Abstract number: P1179

Khanin M., Rakov D. V.

Russian Academy of Sciences, Russia

The purpose of this work is to study thrombin and other factors generation in various clotting factor deficiencies (factors II, V, VIII, IX, X, XI) and to establish the salient features of the activation of coagulation in clotting factor deficiency. A mathematical model for the dynamics of activation of blood coagulation (to thrombin) in the confined space that is open to injured vessel (hematoma) is used. Kinetic constants are determined from the results of biochemical studies. The effect of the activated platelets present on the kinetics of clotting factor activation, including factor XI activation by thrombin, factors XII and XIa is taken into account (Baglia F.A., Walsh P.N., 2000, J. Biol. Chem., vs. 275(27), p. 20514–20519). Maximum thrombin concentration and the time to reach the maxi-mum concentration are chosen to assess thrombin generation. These quantities are also used to establish the sensitivity of coagulation to various clotting factor deficiencies. Maximum thrombin concentration and the time to reach the maximum thrombin concentration are determined as a function of clotting factor deficiency. The sensitivity of thrombin generation to clotting factor deficiency is shown to be practically the same for all the factors considered. A 10-fold deficiency results in only about a 20% decrease in maximum thrombin concentration and about 2-fold prolongation in the time to reach maximum thrombin concentration. For a 100-fold deficiency and more, a significant decrease in thrombin generation is observed, which is in agreement with clinical data (Ried et al. 2002, Thromb. Haemost, 28(4), 576–582). The results obtained indicate a low sensitivity of the coagulation to a large (10–20-fold) deficiency of clotting factors. This property of coagulation might be explained as a specific features of evolutionary nature.