Sequential Formation Of Des-A Fibrin And Des-Ab Fibrin And Binding Of Fibrinogen To Des-Ab Fibrin

Thrombin cleaves the fibrinopeptides A and B from fibrinogen in a consecutive manner, producing first des-A fibrin and consequently, des-AB fibrin. Physico-chemical and in-vivo properties of both types of fibrin were comparatively studied by gel filtration, affinity chromatography and in-vivo behavior. At 37°C and in the presence of fibrinogen and Ca++, des-A fibrin formed soluble fibrin-fibrin dimers. Des-AB fibrin, however, formed oligomers at 37°C. Fibrin-fibrinogen interactions were studied by affinity chromatography. At 37°C, des-A fibrin did not interact with immobilized fibrinogen, whereas des-AB fibrin stuck to it. Small amounts of des-A fibrin iv injected were cleared from the circulation much faster than des-AB fibrin. Large amounts of des-A fibrin injected into animals aggregated to microclots. These results suggest that des-A fibrin in a low concentration (0.01 mg/ml) does not form circulating oligomers and can very fast be cleared from the circulation possibly because of its weak interaction with fibrinogen. Aggregated des-A fibrin, however, is cleaved to form des-AB fibrin. Des-AB fibrin binds fibrinogen making it accessible to further thrombin cleavage. Thus, the threshold of clot formation would be the concentration of des-A fibrin in plasma. The preferential sequence of reactions is: fibrinogen → des-A fibrin → des-A fibrin aggregates → des-AB fibrin aggregates. Des-AB fibrin + fibrinogen → des-AB fibrin-fibrinogen → des-AB fibrin-des-A fibrin etc.