Fibrin assembly in human plasma and fibrinogen/albumin mixtures

Magnetic birefringence is used to monitor the kinetics of thrombin-catalyzed fibrin polymerization in model systems of increasing complexity (i.e., fibrinogen solutions, fibrinogen/albumin mixtures, and plasma anticoagulated with citrate) and in plasma containing free calcium which is the physiological condition. The introduction of albumin into fibrinogen solutions shortens the lag period and enhances fiber thickness. The polymerization progress curves are sigmoidal at zero or low albumin concentrations, but at physiological and higher concentrations, they become hyperbola-like from the end of the lag period. High albumin concentration has thus induced a change in the assembly kinetics. The progress curves from plasma in which the cascade is dormant are also hyperbola-like although they round off more quickly because of antithrombin activity. In plasma containing free calcium, thrombin is endogenously produced, and the progress curves are nearly linear; hence, the assembly kinetics are very different from those of the model systems. The curves are not influenced by calcium-dependent cross-linking involving factor XIIIa. The progress curves are also linear when polymerization is induced with Russell's viper venom, which by directly activating factor X circumvents earlier steps in the cascade. This implies that linear polymerization is caused by events posterior to factor X activation and are thus likely to be largely dependent on the functioning of the prothrombinase complex. Addition of thrombin to plasma containing free calcium reduces the lag period. At low exogenous thrombin levels, the polymerization rate is increased, and the progress curves remain linear. However, at higher levels, the curves become more complicated and, paradoxically, full polymerization takes longer.(ABSTRACT TRUNCATED AT 250 WORDS)