Future Perspectives on the Fibrinolytic Therapy of Intracerebral Hemorrhages

Ruth      Thiex

Abstract

Intracerebral hemorrhage (ICH) is associated with a high mortality and severe disability. Whereas a classical open craniotomy for hematoma removal may further traumatize brain tissue, minimally invasive surgery combines benefits of surgical clot removal with limited tissue damage and shorter surgery duration. Evacuation is often hampered by clot retraction, thus, advocating clot liquefaction to facilitate complete evacuation. The use of urokinase or recombinant tissue plasminogen activator (rtPA) alone and in combination with neuroprotective drugs in experimental studies and clinical trials is reviewed with respect to efficacy in hematoma reduction and effects on secondary brain injury. Whereas rtPA promotes delayed edema formation and inflammation after local fibrinolysis, desmoteplase (DSPA), a highly fibrin-selective plasminogen activator derived from vampire bat saliva, combines high fibrinolytic potential with lack of excitotoxicity, thus representing a novel, promising candidate for fibrinolytic therapy of ICH.

Keywords: Edema formation, excitotoxicity, fibrinolysis, inflammation, intracerebral hemorrhage, plasminogen activator, Brain Edema, Tissue Plasminogen Activator, Desmoteplase, Minimally Invasive Surgery, Hematoma Expansion, Factor VII, Thrombin, Coagulation Cascade, Clot Aspiration, Craniotomy, Endoscopic Hematoma Evacuation, Stereotactic Hematoma Puncture, Microglia, NMDA-receptor Antagonist, MK801, Neuroprotection, Fibrinogen, Pathophysiology, Secondary Brain Injury, Deep-seated Hemorrhage, DSPA