REDUCTION OF PLASMA CLOT STABILITY BY A NOVEL FACTOR XIIIA INHIBITOR FROM THE GIANT AMAZON LEECH, HAEMENTERIA-GHILIANII

The blood-sucking leech, Haementeria ghilianii, has evolved a number o f agents that attenuate haemostasis. Recently me have isolated a poten t inhibitor of factor XIIIa, tridegin, in the salivary glands which is almost certainly involved in feeding. Addition of purified natural tr idegin to plasma, prior to clotting with thrombin, results in clots th at deform more readily as adjudged by the greatly reduced development of the storage modulus on application of a shear force. The increase i n the storage modulus in developing plasma clots is a slow process and continues for many hours. The effect of tridegin is particularly grea t when the clots are permitted to ape in this way, demonstrating the r ole of factor XIIIa in the process. The IC50 for this inhibition is 13 8 ng/ml. Clots formed in the presence of tridegin are also lysed more rapidly in vitro by the leech's own fibrinolytic enzyme, hementin (tim e for 50% lysis, 16.0+/-0.8 h versus 22.3+/-2.0 h, P<0.05). The synerg y with which these agents act together may provide lessons for therapy of thrombosis in man.