Fibrin formation: the role of the fibrinogen-fibrin monomer complex

The process of fibrin formation using highly purified fibrinogen and thrombin was studied using laser fluctuation spectroscopy, a method that rapidly determines particle size in a solution. Two periods in fibrin clot formation were noted: an induction period during which no fibrin polymerization occurred and a period of rapid increase in particle size. Direct measurement of fibrin monomer polymerization and fibrinopeptide release showed no evidence of an induction period. These observations were best explained by a kinetic model for fibrin clot formation incorporating a reversible fibrinogen-fibrin monomer complex. In this model, the complex serves as a buffer system during the earliest phase of fibrin formation. This prevents the accumulation of free polymerizable fibrin monomer until an appreciable amount of fibrinogen has reacted with thrombin, at which point the fibrin monomer level rises rapidly and polymerization proceeds. Clinically, the complex may be a homeostatic mechanism preventing pathological clotting during periods of elevated fibrinogen.