Distribution of intermediate polymers in the fibrinogen-fibrin conversion

The effect of pH and hexamethylene glycol (HMG) on the initial course of the thrombin-fibrinogen reaction has been studied by means of flow birefringence, supplemented by sedimentation velocity measurements. As the polymerization proceeds the distribution of intermediate polymers depends on the pH, there being a significant number of relatively long particles before the gel point between pH 6 and 10 and shorter ones outside of this range. These polymers persist for long periods of time beyond the gel point but are probably ultimately bound into the gel network. Hexamethylene glycol appears to have a dissociating effect on the intermediate polymers. There appear to be many rapidly reversible equilibria between thrombin-activated fibrinogen and intermediate polymers of this activated material. However, not all these equilibria lead to the formation of stable intermediates, the range of stable intermediates depending on the pH. This phenomenon is thought to arise from the same electrostatic effects suggested by Shulman and Ferry (18) to explain the dependence of clotting time on pH in similar systems.