Studies on the Molecular Pathology and Pathogenesis of Bleeding in Severe Fibrinolytic States in Dogs

Summary

1. In the course of fibrinogen digestion by plasmin in a plasma medium in vitro “early” and “late” fibrinogen degradation products (FDP) are formed.

2. The formation of the early FDP is correlated with the appearance of the “peak”, e.g. the highest plasma anticlotting activity. This activity after further FDP digestion with plasmin and formation of late FDP attains lower “plateau” values.

3. A similar effect is observed after SKP1 infusion into dogs.

4. The close similarity between the course of in vitro and in vivo digestion of fibrinogen allows to conclude that, as has been shown in purified systems, early FDP act predominantly as inhibitors of thrombin-fibrinogen reaction, whereas late FDP are responsible for the inhibition of fibrin monomer polymerization.

5. Methods for identification and differentation of circulating FDP are described.

6. The appearance of early FDP circulating in blood is correlated with the most pronounced prolongation of the bleeding time and with prof used bleeding.

7. It has been shown that circulating FDP interference with platelet adhesiveness, aggregation and viscous metamorphosis, the effect of early FDP being more pronounced than that of late FDP.

8. A concept is put forward according to which bleeding in plasma proteolytic states is due to the impairment of hemostatic function of platelets by FDP.

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