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Textilinin‐1, an alternative anti‐bleeding agent to aprotinin: Importance of plasmin inhibition in controlling blood loss
Author(s) -
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.
Publication year - 2009
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2009.07605.x
Subject(s) - aprotinin , plasmin , blood loss , medicine , pharmacology , surgery , chemistry , biochemistry , enzyme
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.