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

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 micromol/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.

• Authors: Simone M Flight, Lambro A Johnson, Qianyun S Du, Roscoe L Warner, Manuela Trabi, Patrick J Gaffney, Martin F Lavin, John de Jersey, Paul P Masci
• Journal: British journal of haematology (Br J Haematol) Vol. 145 Issue 2 Pg. 207-11 (Apr 2009) ISSN: 1365-2141 [Electronic] England
• PMID: 19236611 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Elapid Venoms
• Serine Proteinase Inhibitors
• textilinin
• Aprotinin
• Fibrinolysin

Topics

• Analysis of Variance
• Animals
• Aprotinin (therapeutic use)
• Blood Loss, Surgical (prevention & control)
• Elapid Venoms (therapeutic use)
• Fibrinolysin (antagonists & inhibitors)
• Fibrinolysis (drug effects)
• Hemostasis
• Mice
• Serine Proteinase Inhibitors (therapeutic use)
• Time Factors