Summary
To characterize the duration of the fibrinolytic response to tissue-type plasminogen
activator (t-PA) and streptokinase (SK) in patients with acute myocardial infarction
we serially assayed crosslinked fibrin degradation products (XL-FDP) and Bβ15-42 fibrinopeptide.
Use of specific monoclonal antibodies permitted quantification and differentiation
of fibrin from fibrinogen degradation products. Marked elevations of XL-FDP occurred
within 1 hour after administration of t-PA (n = 13) or SK (n = 35) to >1000 ng/ml
in 79% of the patients. All patients given t-PA exhibited elevations of XL-FDP >1000
ng/ml, most exhibited values >5000 ng/ml (79% of patients). In contrast 6 of the patients
given SK failed to exhibit XL-FDP >1000 ng/ml. XL-FDP >5000 ng/ml occurred in only
14%. The difference in the response to t-PA compared to SK was particularly striking
7 hours or more after administration of activator at which time XL-FDP were markedly
elevated in patients given t-PA (5821 ± 1683 ng/ ml) compared with decreasing values
in patients given SK (2924 ± 1186 ng/ml) (p <0.01). Levels of Bβ315-42 were significantly
higher after t-PA compared with SK beginning 3 hours after treatment, consistent with
a greater intensity of fibrinolytic response to t-PA. Marked elevations of this short
lived degradation product of fibrin (t1/2 = 10-20 minutes) in the samples drawn late after administration of t-PA (44.3 ±12.8
nM) but not after SK (11.7 ± 4.5 nM) confirmed prolonged fibrinolytic activity of
plasmin after t-PA. There was no discernible relationship between the extent of fibrinolysis
as assessed by XL-FDP and Bβ 15-42 and the total dose of t-PA administered or the
duration of the infusion. Elevations of XL-FDP invariably occurred after SK, and were
not significantly different in patients with or without recanalization. Thus “clinical
success” of coronary thrombolysis appears to depend on a favorable balance between
thrombosis and fibrinolysis rather than the intensity of fibrinolysis alone. The prolonged
fibrinolytic activity after t-PA appears to reflect the enhanced binding of this activator
to fibrin and is likely to result in more sustained and hence more effective fibrinolysis
with t-PA compared to SK despite the short half-life of t-PA (t1/2 = 6 minutes) in the circulation.
Keywords
Thrombolysis - Fibrin degradation products - Fibrinopep-tides - Myocardial infarction
