Tridegin, a novel peptidic inhibitor of factor XIIIa from the leech, Haementeria ghilianii, enhances fibrinolysis in vitro.
Tridegin is a potent inhibitor of factor XIIIa from the leech, Haementeria ghilianii, which inhibits protein cross-linking. It modifies plasmin-mediated fibrin degradation as shown by the absence of D-dimer and approximately halves the time for fibrinolysis. Plasma clots formed in the presence of Tridegin lyse more rapidly when either streptokinase, tissue plasminogen activator or hementin is added 2 h after clot formation. The effect of Tridegin is markedly increased if clots are formed from platelet-rich plasma. Platelet-rich plasma clots are lysed much more slowly by the fibrinolytic enzymes used and if Tridegin is present, the rate of lysis returns almost to that of platelet-free clots. These studies indicate the important role of platelets in conferring resistance to commonly used fibrinolytic enzymes and suggest that protein cross-linking is an important step in this effect. Moreover they indicate that Tridegin, a small polypeptide, may have potential as an adjunct to thrombolytic therapy.
Seale
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L
Biopharm (UK) Limited, Hendy, Dyfed, UK.
Finney
S
S
Sawyer
R T
RT
Wallis
R B
RB
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D002417:Cattle; D015956:Factor XIIa / Q000037:antagonists & inhibitors*; D005337:Fibrin / Q000502:physiology; D005340:Fibrinogen / Q000187:drug effects / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D007865:Leeches; D008666:Metalloendopeptidases / Q000494:pharmacology; D013300:Streptokinase / Q000494:pharmacology; D013552:Swine; D010959:Tissue Plasminogen Activator / Q000494:pharmacology
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D005337:Fibrin; D005340:Fibrinogen; D013300:Streptokinase; D015956:Factor XIIa; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D008666:Metalloendopeptidases; C040192:hementin