A comprehensive model for the humoral coagulation network in humans.
Coagulation is an important process in hemostasis and comprises a complicated interaction of multiple enzymes and proteins. We have developed a mechanistic quantitative model of the coagulation network. The model accurately describes the time courses of coagulation factors following in vivo activation as well as in vitro blood coagulation tests of prothrombin time (PT, often reported as international normalized ratio (INR)) and activated partial thromboplastin time (aPTT). The model predicts the concentration-time and time-effect profiles of warfarin, heparins, and vitamin K in humans. The model can be applied to predict the time courses of coagulation kinetics in clinical situations (e.g., hemophilia) and for biomarker identification during drug development. The model developed in this study is the first quantitative description of the comprehensive coagulation network.
Wajima
T
T
School of Pharmacy, University of Otago, Dunedin, New Zealand.
Isbister
G K
GK
Duffull
S B
SB
D000465:Algorithms; D000925:Anticoagulants / Q000493:pharmacokinetics / Q000494:pharmacology*; D001777:Blood Coagulation / Q000502:physiology*; D001780:Blood Coagulation Tests; D003198:Computer Simulation; D006467:Hemophilia A / Q000097:blood; D006490:Hemostatics / Q000493:pharmacokinetics / Q000494:pharmacology; D006493:Heparin / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D019934:International Normalized Ratio; D007700:Kinetics; D008954:Models, Biological; D015233:Models, Statistical; D010314:Partial Thromboplastin Time; D011237:Predictive Value of Tests; D011517:Prothrombin Time; D012909:Snake Bites / Q000097:blood; D014812:Vitamin K / Q000493:pharmacokinetics / Q000494:pharmacology; D014859:Warfarin / Q000493:pharmacokinetics / Q000494:pharmacology
D000925:Anticoagulants; D006490:Hemostatics; D014812:Vitamin K; D014859:Warfarin; D006493:Heparin