Desmoteplase-mediated plasminogen activation and clot lysis are inhibited by the lysine analogue tranexamic acid

Abstract

Tranexamic acid (trans-4-aminoethylcyclohexane-1carboxylic acid; t-AMCA) (TA) is a synthetic lysine analogue with potent antifibrinolytic properties. TA saturates lysine binding sites on kringle domains of plasminogen and prevents them from interacting with the fibrin surface, thereby disrupting plasminogen activation and fibrinolysis [1,2]. TA is used clinically to minimize blood loss in a range of haemorrhagic conditions, mainly during cardiac surgeries or in the treatment of chronic bleeding disorders (e.g. menorrhagia) [2]. TA is also considered in bleeding associated with thrombolytic therapy [3]. Control of systemic fibrinolysis in humans requires a therapeutic plasma TA concentration of 10–15mg/ml (63–95mmol/l) [4,5].