THROMBOLYTIC THERAPY AND PROTEOLYSIS OF FACTOR-V

Objectives. We sought to determine the extent of Factor V proteolysis during thrombolytic therapy. Background. Thrombin- or Factor Xa-activa ted Factor V is an essential cofactor in the prothrombinase complex, I n purified systems, plasmin, the major product of thrombolytic therapy , is known to first activate then inactivate Factor V. Methods. We use d quantitative gel electrophoresis and Western blotting to analyze the cleavages in plasma Factor V after thrombolytic therapy. Results. The addition of streptokin ase to plasma resulted in the activation then inactivation of Factor V, confirming previous results using purified r eagents, We also identified the Factor V fragments resulting from the action of thrombin and plasmin, After thrombolytic therapy, there was considerable Factor V cleavage, The cleavage patterns were consistent with the action of plasmin, with little evidence for the action of thr ombin, In the Global Utilization of Streptokinase and Tissue Plasminog en Activator for Occluded Coronary Arteries trial (n = 17) we observed an average 58% loss of intact Factor V at 6 h (range 1% to 91%). Samp les from the Thrombolysis in Myocardial Infarction trial, Phase II (n = 12), collected on a shorter time scale, showed a loss of up to 99% a t 50 min, with the loss of intact Factor V associated with the plasma concentration of plasminogen activator, Samples from patients with ble eding (n = 12) showed extensive Factor V cleavage. Conclusions. Factor V cleavage in thrombolytic therapy is primarily plasmin mediated, rap id and often extensive. It is likely that transient increases, as well as longer term losses, of Factor V cofactor activity play a role in b oth ischemic and hemorrhagic events subsequent to thrombolytic therapy , The extensive loss of Factor V in some patients may affect the estim ation of heparinization. (C) 1997 by the American College of Cardiolog y.