Degradation of Fibrinogen by Proteolytic Enzymes

Summary

Degradation products of fibrinogen and fibrin resulting from the hydrolytic action of plasmin, trypsin, chymotrypsin and papain were prepared and the two major polypeptide fragments were found to have inhibitory effects on the coagulation mechanism including inhibition of thromboplastin generation and inhibition of the conversion of the fibrinogen to fibrin. The inhibitory actions of each of the isolated components were characterized specifically for their role in each of these coagulation functions.

Both the slow (D) and fast (E) fragments of fibrinogen and fibrin hydrolysis by plasmin degradation showed equally inhibitory effects against fibrinogen to fibrin conversion by thrombin and fibrin monomer polymerization. The slow component of both was more inhibitory. Both fast and slow digestion products of tryptic hydrolysis inhibited thromboplastin generation and fibrinogen to fibrin conversion and fibrin monomer polymerization equally. The fast component of chymotrypsin hydrolysis showed greater inhibition against thromboplastin generation and fibrin monomer polymerization, than did the slow component. Only a slow moving (D) component was obtained with papain digestion. It had no inhibitory function against thromboplastin generation and only minimal effect against fibrin monomer polymerization. The mechanism of inhibition of the thromboplastin generation test by fibrinogen degradation products is a neutralization or inhibition of factor IX.

^* Supported by Grants CA-05588 and HE-05147 from the National Institutes of Health.

¹ Director of Oncology, Maimonides Medical Center and Assistant Professor of Medicine, State University of New York, Downstate Medical Center. Present address: Brooklyn Cumberland Medical Center, 39 Auburn, Place Brooklyn, N. Y. 11201.

² Fellow in Oncology, Maimonides Medical Center, 1963–1964.

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