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Textilinin-1, an alternative anti-bleeding agent to aprotinin: Importance of plasmin inhibition in controlling blood loss

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Abstract:

Summary

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.

Keywords: anti-bleeding; anti-fibrinolytic; aprotinin; serine protease inhibitor; textilinin-1

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1365-2141.2009.07605.x

Affiliations: 1: School of Medicine, University of Queensland, Brisbane, Australia 2: Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA 3: Academic Department of Surgery, St Thomas’s Hospital, London, UK 4: School of Chemical and Molecular Biosciences Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia

Publication date: April 1, 2009

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