[Mechanism of inhibition of fibrin polymerization by fibrinogen and its active fragments].

The specific inhibition of fibrin monomer polymerization by fibrinogen and some of its degradation products shows an unusual concentration dependence. Namely, in a certain region of the inhibitor concentration scale the slope of the activity curve increases considerably with an increase in concentration to reach a high constant steepness. This peculiar relationship indicates that the mechanism of inhibition is rather complicated. It has been assumed that this mechanism includes two steps: the first, preliminary step can presumably consist in an inhibitor induced transformation of fibrin (monomer or rather intermediate polymers), while the second one--a competitively inhibiting complex formation. At low inhibitor concentrations the rate of fibrin transformation is slow and limits the delay in clotting. At higher concentrations the modification is progressively accelerated and its rate gradually ceases, influencing the extent of the inhibition. The second stage, with its linear concentration dependence, becomes therefore exclusively rate-limiting. A kinetic analysis revealed that three molecules of the inhibitor are involved in the fibrin modification act. The theoretical curve obtained on the basis of the two-step model was found to be in good agreement with the experimental data.