Plasmin: A driver of hemovascular dysfunction

Abstract

In this issue of Blood, Marcos-Contreras and colleagues present convincing evidence that mechanistically links hyperfibrinolysis, typically seen as a bleeding risk, with increased brain endothelial permeability through plasmin-mediated cleavage of high-molecular-weight kininogen (HMWK) to bradykinin (BK). This study establishes plasmin as a key effector of what might be termed "hemovascular dysfunction": a pathological state of blood enzymatic activity resulting in vascular structural and functional disruption. Their findings point the way toward improved treatment of patients with pharmacologically (stroke and myocardial infarction) or pathologically activated fibrinolysis (trauma and surgery) through selective blockade of bradykinin activity. Combined blockade of bradykinin and plasmin activation may provide additional therapeutic benefits in hemorrhagic shock by reducing tissue edema in resuscitation while enhancing hemostasis.