PATHOGENESIS OF THE COAGULATION DEFECT DEVELOPING DURING PATHOLOGICAL PLASMA PROTEOLYTIC (“FIBRINOLYTIC”) STATES. II. THE SIGNIFICANCE, MECHANISM AND CONSEQUENCES OF DEFECTIVE FIBRIN POLYMERIZATION*

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Abstract
Patients, suffering from pathological plasma proteolytic ("fibrinolytic") states, develop as a consequence of fibrinogen proteolysis, a coagulation defect, dependent on the presence in plasma of fibrinogen proteolysis products. The two major coagulation anomalies observed are increase of the thrombin clotting time and a macroscopically apparent defect in clot appearance and character. The enzymatic actions of thrombin measured on the substrates BAMe (benzoylarginine methyl ester) and fibrinogen were not inhibited by the presence of fibrinogen proteolysis products; consequently it would be inferred that fibrinogen proteolysis products inhibit the polymerization-gelation phase of coagulation. This inference was confirmed by the use of modified light-scattering procedures. Fractionation of fibrinogen digests, by several means, revealed that a single large moelcular weight fibrinogen fragment (5.27 S20w).itself resistant to enzymatic digestion by plasmin or trypsin was predominantly responsible for inhibition of fibrin polymerization. Analysis of clots formed from plasma containing fibrinogen proteolysis products revealed that the large molecular weight fibrinogen fragment (5.27 S20w) was preferentially incorporated into clots and that the extent of such incorporation parallelled the severity of the coagulation defect. Consequently the biochemical lesion responsible for the coagulation anomaly has been termed defective fibrin polymerization.