Textilinin-1, an alternative anti-bleeding agent to aprotinin: Importance of plasmin inhibition in controlling blood loss.
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.
Flight
Simone M
SM
School of Medicine, University of Queensland, Brisbane, Australia.
Johnson
Lambro A
LA
Du
Qianyun S
QS
Warner
Roscoe L
RL
Trabi
Manuela
M
Gaffney
Patrick J
PJ
Lavin
Martin F
MF
de Jersey
John
J
Masci
Paul P
PP
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
D004546:Elapid Venoms; D015842:Serine Proteinase Inhibitors; C413544:textilinin; D007611:Aprotinin; D005341:Fibrinolysin