Changes In The Antithrombin III Activity At The Interface Plasma-Phospholipids

The role of antithrombin III (AT III) on kinetics of thrombin activity was studied in an inhibitor free coagulation system in which purified AT III was added at various concentrations. Coagulation was initiated either by kaolin or by Stypven in the presence of phospholipids. Kinetics of the respective activities of factor Xa and thrombin were followed on chromogenic substrates S-2222 and S-2238 and on fibrinogen for the latter.

These experiments gave the following results : (i) kinetics of thrombin formation as well as the peak level of thrombin activity were strongly dependent on AT III concentration ; (ii) Xa formation was unaffected by AT III level ; moreover the decrease of Xa activity was much slower than that of thrombin and was negatively correlated with phospholipid concentration.

These results illustrate the impact on blood coagulation of minor deviations from normal of AT III level. This assumption was confirmed by AT III infusion to normal subjects. On the other hand our findings cast doubt on the physiological importance of the inhibitory activity of AT III on serine-proteases other than thrombin. At the interface piasma/phospholipids, when complexed with phospholipids and protein cofactors (i.e. factors V and VIII) the affinity of the enzymes for the inhibitor becomes negligible compared to their affinity towards their respective zymogen substrates. In a complete coagulation system, inhibition of thrombin formation by AT III seems to result mainly from the inhibition of the cooperative action of thrombin on its own formation.