Identification of the mechanism responsible for the decreased fibrin specificity of reteplase relative to tissue-type plasminogen activator

Reteplase (r-PA), a truncated variant of tissue-type plasminogen activator (t-PA) consisting of the second kringle and protease domains, is now used for treatment of acute myocardial infarction (AMI). At equally effective doses, r-PA causes more fibrinogen (Fg) consumption than t-PA. Recently, we demonstrated that Fg stimulates t-PA-mediated plasminogen (Pg) activation, albeit weakly, because t-PA binds Fg via its second kringle domain. In this …