Mathematical modeling of blood coagulation cascade: kinetics of intrinsic and extrinsic pathways in normal and deficient conditions

A mathematical model has been developed to simulate the generation of thrombin through intrinsic and extrinsic pathways. The time course of clotting factor activation during coagulation was calculated, and the sensitivity of the kinetics due to a decrease or deficiency in the concentrations of coagulation proteins or their activities was studied. The model gives reasonable predictions without the adjustment of any parameter values. The calculated clotting time was approximately 44 s for the intrinsic pathway and approximately 8.6 s for the extrinsic pathway using normal protein concentrations in plasma. Various prolonged clotting times were observed in different factor-deficient disorders using this model.

[1]  D D Monkovic,et al.  Activation of human factor V by factor Xa and thrombin. , 1990, Biochemistry.

[2]  J. Vilpo,et al.  Poor agreement among prothrombin time international normalized ratio methods: comparison of seven commercial reagents. , 2005, Clinical chemistry.

[3]  J. Finlayson,et al.  Kinetics of activation and autoactivation of human factor XII. , 1984, Biochemistry.

[4]  K Fujikawa,et al.  The coagulation cascade: initiation, maintenance, and regulation. , 1991, Biochemistry.

[5]  J Jesty,et al.  Kinetics of the inhibition of factor Xa and the tissue factor-factor VIIa complex by the tissue factor pathway inhibitor in the presence and absence of heparin. , 1994, Biochemistry.

[6]  J. Shafer,et al.  Steady state kinetic parameters for the thrombin-catalyzed conversion of human fibrinogen to fibrin. , 1983, The Journal of biological chemistry.

[7]  K. Mann,et al.  Human prothrombinase complex assembly and function on isolated peripheral blood cell populations. , 1985, The Journal of biological chemistry.

[8]  K. Mann,et al.  Radioimmunoassay of factor V in human plasma and platelets. , 1982, Blood.

[9]  K. Mann,et al.  Biochemistry and Physiology of Blood Coagulation , 1999, Thrombosis and Haemostasis.

[10]  H. Saito,et al.  Impaired human tissue factor-mediated activity in blood clotting factor VIINagoya (Arg304-->Trp). Evidence that a region in the catalytic domain of factor VII is important for the association with tissue factor. , 1994, The Journal of biological chemistry.

[11]  S. Bajaj,et al.  Intrinsic versus extrinsic coagulation. Kinetic considerations. , 1986, The Biochemical journal.

[12]  J. Griffin,et al.  Interaction of type 1 plasminogen activator inhibitor with the enzymes of the contact activation system. , 1989, The Journal of biological chemistry.

[13]  G. Krishnan Radioimmunoassay for human prothrombin. , 1983, Clinical chemistry.

[14]  A. Kolstø,et al.  Cell biology of tissue factor, the principal initiator of blood coagulation. , 1996, Thrombosis research.

[15]  M. Hultin Role of human factor VIII in factor X activation. , 1982, The Journal of clinical investigation.

[16]  Kenneth G. Mann,et al.  An Integrated Study of Fibrinogen during Blood Coagulation* , 1999, The Journal of Biological Chemistry.

[17]  K Fujikawa,et al.  Activation of human blood coagulation factor XI independent of factor XII. Factor XI is activated by thrombin and factor XIa in the presence of negatively charged surfaces. , 1991, The Journal of biological chemistry.

[18]  J. Miletich,et al.  Purification and characterization of the lipoprotein-associated coagulation inhibitor from human plasma. , 1989, The Journal of biological chemistry.

[19]  O. Ratnoff,et al.  A new method for the determination of fibrinogen in small samples of plasma. , 1951, The Journal of laboratory and clinical medicine.

[20]  F I Ataullakhanov,et al.  A mathematical model for the spatio-temporal dynamics of intrinsic pathway of blood coagulation. I. The model description. , 1996, Thrombosis research.

[21]  A. Rezaie,et al.  Activation of protein C by the thrombin-thrombomodulin complex: cooperative roles of Arg-35 of thrombin and Arg-67 of protein C. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[22]  R. Colman,et al.  The regulation of human factor XIIa by plasma proteinase inhibitors. , 1985, The Journal of biological chemistry.

[23]  H. Suomela Human coagulation factor IX. Isolation and characterization. , 1976, European journal of biochemistry.

[24]  I. F. Obraztsov,et al.  A Mathematical Model of the Background State of the Blood Coagulation System , 2004, Doklady Biochemistry and Biophysics.

[25]  M. Shuman,et al.  Cleavage of blood coagulation factor XIII and fibrinogen by thrombin during in vitro clotting. , 1985, The Journal of clinical investigation.

[26]  G. Broze,et al.  Factor XI activation in a revised model of blood coagulation , 1991, Science.

[27]  M. Verstraete,et al.  Metabolism of antithrombin III (heparin cofactor) in man: effects of venous thrombosis and of heparin administration , 1977, European journal of clinical investigation.

[28]  E. Komives,et al.  Electrostatic dependence of the thrombin-thrombomodulin interaction. , 2000, Journal of molecular biology.

[29]  E. Kruithof,et al.  Plasminogen Activator Inhibitor 1 and Plasminogen Activator Inhibitor 2 in Various Disease States , 1988, Thrombosis and Haemostasis.

[30]  M. Schenone,et al.  The blood coagulation cascade , 2004, Current opinion in hematology.

[31]  M A Khanin,et al.  Analysis of the activated partial thromboplastin time test using mathematical modeling. , 2001, Thrombosis research.

[32]  S. Rapaport,et al.  Radioimmunoassays for protein C and factor X. Plasma antigen levels in abnormal hemostatic states. , 1984, American journal of clinical pathology.

[33]  F I Ataullakhanov,et al.  A mathematical model for the spatio-temporal dynamics of intrinsic pathway of blood coagulation. II. Results. , 1996, Thrombosis research.

[34]  K. Mann,et al.  Activation of human prothrombin by human prothrombinase. Influence of factor Va on the reaction mechanism. , 1987, The Journal of biological chemistry.

[35]  F Keller,et al.  The quick machine--a mathematical model for the extrinsic activation of coagulation. , 1994, Haemostasis.

[36]  P. Lollar,et al.  von Willebrand factor is a cofactor for thrombin-catalyzed cleavage of the factor VIII light chain. , 1990, The Journal of biological chemistry.

[37]  H C Hemker,et al.  The role of phospholipids and factor Va in the prothrombinase complex. , 1980, The Journal of biological chemistry.

[38]  J. Griffin,et al.  Human blood coagulation factor XI. Purification, properties, and mechanism of activation by activated factor XII. , 1977, The Journal of biological chemistry.

[39]  M. Scully,et al.  Inhibition of prothrombinase complex by plasma proteinase inhibitors. , 1984, Biochemistry.

[40]  K. Mann,et al.  A model for the tissue factor pathway to thrombin. II. A mathematical simulation. , 1994, Journal of Biological Chemistry.

[41]  S. Olson,et al.  High molecular weight kininogen potentiates the heparin-accelerated inhibition of plasma kallikrein by antithrombin: role for antithrombin in the regulation of kallikrein. , 1993, Biochemistry.

[42]  K. Mann,et al.  Complex-dependent inhibition of factor VIIa by antithrombin III and heparin. , 1993, The Journal of biological chemistry.

[43]  M. Poon,et al.  Human plasma prekallikrein (Fletcher factor) clotting activity and antigen in health and disease. , 1978, The Journal of laboratory and clinical medicine.

[44]  N. Vaziri,et al.  Increased levels of protein C activity, protein C concentration, total and free protein S in nephrotic syndrome. , 1988, Nephron.

[45]  Y. Aso,et al.  Relationship between soluble thrombomodulin in plasma and coagulation or fibrinolysis in type 2 diabetes. , 2000, Clinica chimica acta; international journal of clinical chemistry.

[46]  P. Walsh,et al.  Kinetics of coagulation factor X activation by platelet-bound factor IXa. , 1990, Biochemistry.

[47]  J. Travis,et al.  Kinetics of association of serine proteinases with native and oxidized alpha-1-proteinase inhibitor and alpha-1-antichymotrypsin. , 1980, The Journal of biological chemistry.

[48]  B. Lämmle,et al.  A quantitative dot immunobinding assay for coagulation factor XII in plasma. , 1990, Journal of immunological methods.

[49]  R. Colman,et al.  Inactivation of factor XII active fragment in normal plasma. Predominant role of C-1-inhibitor. , 1984, The Journal of clinical investigation.

[50]  M A Khanin,et al.  Mathematical model for the blood coagulation prothrombin time test. , 1998, Thrombosis research.

[51]  A. Schmaier,et al.  Contact system: a vascular biology modulator with anticoagulant, profibrinolytic, antiadhesive, and proinflammatory attributes. , 1997, Blood.

[52]  Mikhail A. Panteleev,et al.  Mathematical Modeling and Computer Simulation in Blood Coagulation , 2006, Pathophysiology of Haemostasis and Thrombosis.

[53]  G M Oosta,et al.  The kinetics of hemostatic enzyme-antithrombin interactions in the presence of low molecular weight heparin. , 1980, The Journal of biological chemistry.