Discreplasminin, a plasmin inhibitor isolated from Tityus discrepans scorpion venom

Tityus discrepans venom (TdV) produces digestive hemorrhages, disseminated intravascular coagulation, alveoli fibrin deposition and/or prothrombin and partial thromboplastin time alterations in humans. T. discrepans venom presents an in vitro tissue plasminogen activator-like (tPA-like), fibrino(geno)lytic and plasmin inhibitory activities. The plasmin inhibitor, called discreplasminin, was isolated from TdV. Discreplasminin has a pI of 8.0 and a relative molecular weight of < 6,000 Da. Discreplasminin and aprotinin strongly inhibited plasmin activity and moderately tPA activity, while epsilon amino caproic acid (EACA) moderately inhibited both enzymes. In presence and absence of fibrin, the plasmin generation by tPA was completely inhibited by aprotinin and discreplasminin. EACA in the absence of fibrin partially inhibited plasmin generation (37%); however, it produced a total inhibition of plasmin generation on a fibrin surface. The tPA-clot lysis assay showed that discreplasminin acts like aprotinin inducing a slight delay in lysis time and lysis rate; in contrast, EACA presented a total inhibitory effect on fibrin lysis. These results suggest that discreplasminin presents an anti-fibrinolytic mechanism similar to aprotinin. Discreplasminin probably interacts with the active sites of plasmin and tPA. The presence of discreplasminin and other similar components in scorpion venom could partially explain the generalized fibrin deposition which was found previously in rams.