Sustained fibrinolysis after administration of t-PA despite its short half-life in the circulation

P. R. Eisenberg, L. A. Sherman, A. J. Tiefenbrunn, P. A. Ludbrook, B. E. Sobel, Allan S Jaffe

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Abstract

To characterize the duration of the fibrinolytic response to tisue-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 Bβ15-42 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 (t( 1/2 ) = 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 Bβ15-42 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 (t( 1/2 ) = 6 minutes) in the circulation.

Original languageEnglish (US)
Pages (from-to)35-40
Number of pages6
JournalThrombosis and Haemostasis
Volume57
Issue number1
StatePublished - 1987
Externally publishedYes

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Plasminogen Activators
Fibrinolysis
Half-Life
Streptokinase
Fibrin Fibrinogen Degradation Products
formycin diphosphate
Fibrinolysin
Fibrin
Thrombosis
Myocardial Infarction

ASJC Scopus subject areas

  • Hematology

Cite this

Eisenberg, P. R., Sherman, L. A., Tiefenbrunn, A. J., Ludbrook, P. A., Sobel, B. E., & Jaffe, A. S. (1987). Sustained fibrinolysis after administration of t-PA despite its short half-life in the circulation. Thrombosis and Haemostasis, 57(1), 35-40.

Sustained fibrinolysis after administration of t-PA despite its short half-life in the circulation. / Eisenberg, P. R.; Sherman, L. A.; Tiefenbrunn, A. J.; Ludbrook, P. A.; Sobel, B. E.; Jaffe, Allan S.

In: Thrombosis and Haemostasis, Vol. 57, No. 1, 1987, p. 35-40.

Research output: Contribution to journalArticle

Eisenberg, PR, Sherman, LA, Tiefenbrunn, AJ, Ludbrook, PA, Sobel, BE & Jaffe, AS 1987, 'Sustained fibrinolysis after administration of t-PA despite its short half-life in the circulation', Thrombosis and Haemostasis, vol. 57, no. 1, pp. 35-40.
Eisenberg, P. R. ; Sherman, L. A. ; Tiefenbrunn, A. J. ; Ludbrook, P. A. ; Sobel, B. E. ; Jaffe, Allan S. / Sustained fibrinolysis after administration of t-PA despite its short half-life in the circulation. In: Thrombosis and Haemostasis. 1987 ; Vol. 57, No. 1. pp. 35-40.
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