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- Title
Textilinin-1, an alternative anti-bleeding agent to aprotinin: Importance of plasmin inhibition in controlling blood loss.
- Authors
Flight, Simone M.; Johnson, Lambro A.; Du, Qianyun S.; Warner, Roscoe L.; Trabi, Manuela; Gaffney, Patrick J.; Lavin, Martin F.; de Jersey, John; Masci, Paul P.
- Abstract
Aprotinin has been used widely in surgery as an anti-bleeding agent but is associated with a number of side effects. We report that textilinin-1, a serine protease inhibitor from Pseudonaja textilis venom with sequence relatedness to aprotinin, is a potent but reversible plasmin inhibitor and has a narrower range of protease inhibition compared to aprotinin. Like aprotinin, textilinin-1 at 5 μmol/l gave almost complete inhibition of tissue plasminogen activator-induced fibrinolysis of whole blood clots. The activated partial thromboplastin time for plasma was markedly increased by aprotinin but unaffected by textilinin-1. In a mouse tail-vein bleeding model, intravenous textilinin-1 and aprotinin caused similar decreases in blood loss but time to haemostasis in the textilinin-treated animals was significantly shorter than in aprotinin-treated mice. Based on these data, textilinin-1 merits further investigation as a therapeutic alternative to aprotinin.
- Subjects
ANTICOAGULANTS; HEMOSTASIS; VENOM; TRYPSIN inhibitors; BLOOD plasma
- Publication
British Journal of Haematology, 2009, Vol 145, Issue 2, p207
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/j.1365-2141.2009.07605.x