Blood cells participate in the fibrinolytic response to tissue-type plasminogen activator

Exercise and venous occlusion stimulate fibrinolysis. In addition to increased concentrations of tissue-type plasminogen activator (tPA) and increased plasmin-mediated fibrinolysis in plasma, these stimuli produce additional cellular-phase activity in blood that is of the same magnitude as the plasma response. To determine whether tPA alone, rather than other consequences of these stimuli, is responsible for the cellular response, the in vitro effects of tPA on whole blood, plasma, and calculated cellular-phase (whole blood minus plasma) activities were determined by solid-phase radiofibrin assay on venous blood from ten normal subjects (seven men, three women). At tPA concentrations encompassing physiological and therapeutic levels (5 to 100 ng/mL; 0.7 to 14 IU/mL), increments in whole blood were consistently in excess of those in companion plasma and represented increased cellular-phase activity equivalent in magnitude to the well-known increase in plasma activity. Fibrinolytic activity produced by 10 to 20 ng tPA/mL (1.4 to 2.8 IU/mL) was consistently detected in whole blood and plasma by 60 minutes, with higher concentrations (100 ng or 14 IU tPA/mL) detectable after a five-minute assay in all subjects. Thus, tPA alone, without invoking fibrinolytic factors extraneous to blood or other effects of exercise or venous occlusion, accounts for both cellular and plasma responses to these stimuli. The considerable cellular response, the mechanism of which remains to be elucidated, may constitute a determinant of individual therapeutic responsiveness to tPA.