title: 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.affiliation: School of Medicine, University of Queensland, Brisbane, Australia.
authors.forename: Simone M
authors.initials: SM
authors.lastname: Flight
authors.forename: Lambro A
authors.initials: LA
authors.lastname: Johnson
authors.forename: Qianyun S
authors.initials: QS
authors.lastname: Du
authors.forename: Roscoe L
authors.initials: RL
authors.lastname: Warner
authors.forename: Manuela
authors.initials: M
authors.lastname: Trabi
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Gaffney
authors.forename: Martin F
authors.initials: MF
authors.lastname: Lavin
authors.forename: John
authors.initials: J
authors.lastname: de Jersey
authors.forename: Paul P
authors.initials: PP
authors.lastname: Masci
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D007611:Aprotinin / Q000627:therapeutic use*; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D004546:Elapid Venoms / Q000627:therapeutic use*; D005341:Fibrinolysin / Q000037:antagonists & inhibitors*; D005342:Fibrinolysis / Q000187:drug effects; D006487:Hemostasis; D051379:Mice; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D004546:Elapid Venoms; D015842:Serine Proteinase Inhibitors; C413544:textilinin; D007611:Aprotinin; D005341:Fibrinolysin