Inhibitors of fibrinolysis: evidence of some instances of mutual potentiation.

Inhibitors of fibrinolysis may be divided into naturally circulating inhibitors and antifibrinolytic agents. Natural inhibitors are present in plasma and are components of blood cells, especially platelets. Several types of antifibrinolytic activity can be distinguished: antiplasmin activity, and anti-activator activity against streptokinase, urokinase, and tissue activator induced plasminogen activation. Antiprotease activities in the blood are mainly attributed to M2 macroglobulin (mw 800 000), an immediate plasmin inhibitor, and to o1 antitrypsin (mw 40-71 000), a progressive plasmin inhibitor. Progressive antiplasmin activity seems also to be localized in the zone of 'inter -o' antitrypsin. Recent investigations have shown that antitrypsin activity in plasma is a very complex system with genetically controlled individual variations (Fagerhol, 1971). Anti-activators againsts treptokinase, urokinase, and tissue activator certainly represent three different inhibiting 'activities' but there is still some question whether they are really three different substances or rather the result of peculiar interactions between antiplasmins. Accordingly antiurokinase and anti-tissue activator activities could be a result of the interaction of O2 macroglobulin and acx antitrypsin, while anti-streptokinase activity could be a function of O2 macroglobulin alone (Spottl, 1970). In contrast, the work of Dr Nilsson's group reported at this meeting suggests the existence of anti-activators as individual substances differing from antiplasmins. Antifibrinolytic activity in platelets is not more than 10% of the whole plasma activity. Both oc, antitrypsin and factor XIII or a similar protein seems to be involved in the antifibrinolytic activity of platelets. The patho-physiological significance of the naturally circulating inhibitors of fibrinolysis is still under discussion. It may be recalled that an increase of antiplasmin activity has been observed