Circulation, Vol 78, 592-597, Copyright © 1988 by American Heart Association
PR Eisenberg, BE Sobel and AS Jaffe
Development of appropriate clinical dose regimens of individual plasminogen
activators such as tissue-type plasminogen activator (t-PA) has generally
relied primarily on nonpharmacological endpoints such as angiographically
documented clot lysis. The recent availability of monoclonal antibodies
that differentiate products of plasmin lysis of fibrin from those of lysis
of fibrinogen should permit delineation of the relative fibrin specificity
of different plasminogen activators or of different doses of the same
activator in vivo. Thus, their use should accelerate and facilitate
development of implementation of optimal dose regimens for diverse
activators and combinations of activators. The present study was designed
to determine whether assay of such markers effectively differentiates
effects of two doses of t- PA, each of which are comparably effective in
opening infarct-related arteries, in patients studied at the Washington
University Clinical Unit of the National Institutes of Health-sponsored
Thrombolysis in Myocardial Infarction Trial. The extent of lysis of fibrin
and of lysis of fibrinogen by plasmin resulting from administration of t-PA
was evaluated in 19 patients given 150 mg t-PA over 6 hours and 17 given
100 mg over the same interval by assay of serially obtained plasma samples
for crosslinked fibrin degradation products (XL-FDP) and B beta 1-42, a
peptide released when fibrinogen is degraded to fragment X by plasmin.
XL-FDP were markedly elevated after 6-hour infusions of both doses of t-PA.
However, elevations were not more with the higher dose [peak value, 4,321
+/- 986 ng/ml (+/- SEM)] compared with the lower dose (3,397 +/- 1,096
ng/ml) (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Characterization in vivo of the fibrin specificity of activators of the fibrinolytic system
Cardiovascular Division, Washington University School of Medicine, St. Louis, MO 63110.