In vitro factor XI activation mechanism according to an optimized model of activated partial thromboplastin time test.
Whether the in vitro activation of factor XI in plasma is mediated by thrombin or by auto-activation remains a controversial question. In this context, we have simulated theoretical activated partial thromboplastin time (aPTT) by means of a program based on a body of 22 essential elementary reactions implemented with rate constants quoted in current literature. To meet self-consistency in input data issued from varying sources, the results were optimized using the simplex treatment. The performance of the model was systematically evaluated considering the extent of the deviations observed between predicted aPTT and laboratory measurements conducted on normal and factor VIII, IX, XI and XII single-factor deficient plasma. The influence of the auto-activation or thrombin-mediated activation of factor XI on these aPTTs was tested separately after insertion of these reactions in the model. According to the best fits, a mechanism accounting for an auto-activation reaction of activated factor XI rather than a positive feedback reaction mediated by thrombin seemed more likely. Based on this conclusion, a chart of self-consistent rate constant values accounting for the intrinsic pathway of coagulation under static conditions is proposed.
Kramoroff
A
A
Université de Cergy-Pontoise, France.
Nigretto
J M
JM
D001777:Blood Coagulation; D005172:Factor XI / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D010314:Partial Thromboplastin Time
D005172:Factor XI