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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.
AuthorsSimone 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
JournalBritish journal of haematology (Br J Haematol) Vol. 145 Issue 2 Pg. 207-11 (Apr 2009) ISSN: 1365-2141 [Electronic] England
PMID19236611 (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

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