title: Sustained fibrinolysis after administration of t-PA despite its short half-life in the circulation.
abstract: 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 B beta 15-42 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 greater than 1000 ng/ml in 79% of the patients. All patients given t-PA exhibited elevations of XL-FDP greater than 1000 ng/ml, most exhibited values greater than 5000 ng/ml (79% of patients). In contrast 6 of the patients given SK failed to exhibit XL-FDP greater than 1000 ng/ml. XL-FDP greater than 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 less than 0.01). Levels of B beta 15-42 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.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D001822:Body Burden; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy; D013300:Streptokinase / Q000008:administration & dosage / Q000494:pharmacology; D013927:Thrombosis / Q000188:drug therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D013300:Streptokinase; D010959:Tissue Plasminogen Activator