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.