A review.Thrombus lysis is the consequence of a restricted number of reactions localized to the surface of fibrin.A functional defect or an insufficient fibrinolytic response may lead to thrombosis with severe or fatal clin. consequences, e.g. myocardial infarction and ischemic stroke.Despite this clin. exigency and real progress in the knowledge of the different components of this system (plasminogen and its activators, inhibitors and receptors), its functional evaluation still remains a challenge in hemostasis.The absolute requirement of a template for mol. assembly of plasminogen and its activators (tissue- and urokinase-type plasminogen activators: tPA and uPA) restricts the formation of plasmin and protection of its activity to the surface of, resp., fibrin and cells.In contrast, plasmin and tPA released from the clot during its lysis are immediately neutralized by their resp. inhibitors α2-antiplasmin and plasminogen activator inhibitor 1 (PAI-1).It seems therefore almost impossible to detect fibrinolytic activity in plasma with methods currently in use.Because of its unavailability, it is also impossible to measure the degree of fibrinolysis directly on the clot.Notwithstanding, it was recently discovered that circulating membrane microvesicles might be indicators of the fibrinolytic response to an inflammatory or prothrombotic process.These cell-derived fibrinolytic microvesicles bear at their membrane the plasminogen activators expressed by the parent cell: tPA from endothelial cells and uPA from leukocytes.These mols. are localized at the membrane surface and have the capacity to activate plasminogen into plasmin in situ.Moreover, it was recently discovered that these microvesicles might participate in a new mechanism of plasmin formation requiring cross-talk between two different surfaces.In this fibrinolytic cross-talk, one of the surfaces bears plasminogen (fibrin, extracellular matrix or platelets) whereas the other surface carries the plasminogen activator, typically leukocyte-derived microvesicles bearing uPA.These new actors and concepts in plasminogen activation represent hitherto unknown pathways in our comprehension of fibrinolysis and potential novel biomarkers in clin. practice.