Soluble fibrin-fibrinogen complexes as intermediates in fibrin gel formation

Oligomer formation in fibrinogen solutions following addition of thrombin was studied by addition of thrombin inhibitor at various times subsequent to thrombin, followed by size-exclusion chromatography (SEC) on a high-performance SEC column capable of resolving species of molecular weights less than or equal to 10(6). Peaks corresponding to species with 1, 2, 3, and 4 or more times the molecular weight of fibrinogen were detected and quantified via nonlinear least-squares curve-fitting procedures. The evolution of each of these peaks with time is well accounted for by a kinetic model in which the predominant component of each oligomeric molecular weight species is a linear complex of fibrinogen and fibrin. The observed predominance of trimeric over dimeric oligomers even at short times suggests that the thrombin-catalyzed release of the two A fibrinopeptides from a single molecule of fibrinogen is highly cooperative.