Intrinsic coagulation pathway: An activation threshold

The activation threshold for the intrinsic pathway of coagulation was experimentally determined in stirred recalcified plasma from the dependence of plasma clotting time after activation by celite. Concentration of factor XIa was used as a measure of activation. At free calcium concentrations below 0.35 mM, plasma clotting time depended nonlinearly on the factor XIa concentration: with decreasing concentration of factor XIa (or celite), the clotting time dramatically increased until no coagulation was observed at concentrations of factor XIa below the threshold. As the free calcium concentration increased, the threshold concentration of factor XIa sharply decreased, from 30 pM at 0.35 mM free calcium to less than 3 pM at 0.35 mM. In the range of free calcium concentrations from 0.45 mM to physiologic ones, plasma coagulated even in the absence of celite in plastic cuvettes. This fact and extremely low threshold concentrations of factor XI (on the order of 0.5 pM) preclude determining the factor XI threshold at physiologic free calcium. As factor XIa is localized to the activating surfaces, observing the local surface concentrations of factor XIa and the dynamics of fibrin formation in systems without stirring may solve the problem. (C) 2000 Elsevier Science Ltd. All rights reserved.