Induction of marked thrombin activity by pharmacologic concentrations of plasminogen activators in nonanticoagulated whole blood.
Thrombin activity reflected by increased plasma concentrations in vivo of fibrinopeptide A (FPA) increases when streptokinase (SK) is administered to patients with acute myocardial infarction. Although procoagulant effects have been found in vitro, the use of anticoagulated plasma limits the extent to which the phenomena observed can be viewed to implicate procoagulant effects in vivo. Accordingly, we characterized the procoagulant effects of SK and tissue plasminogen activator (t-PA) in nonanticoagulated whole blood. Blood was collected from normal volunteers by venipuncture (No. 19 gauge steel needle) directly into polypropylene tubes containing either t-PA, SK, SK and heparin, t-PA and heparin, or saline. The concentration of FPA after 10 min of incubation with saline was 150 +/- 46 nM (n = 14)(SE). In contrast, in blood incubated with SK FPA was consistently and markedly increased after 10 min: 2318 +/- 416 nM (100 IU/ml SK) and 10,889 +/- 1156 nM (1000 IU/ml SK) (p less than 0.001 compared with control). Less marked elevations of FPA occurred after 10 min in blood incubated with t-PA (3171 +/- 604 nM with 2500 ng/ml t-PA, p less than 0.01 compared with 1000 IU/ml SK). Increases in FPA were less than 100 nM in blood incubated with activators and heparin. The extent to which plasminogen was activated, as measured by the release of the B beta 1-42 fibrinopeptide, was related to the magnitude of elevation of FPA. Procoagulant activity induced by extensive plasminogen activation may contribute to undesirable effects in vivo, such as a propensity to recurrent thrombosis or delayed fibrinolysis.
Eisenberg
P R
PR
Cardiovascular and Laboratory Medicine Division, Washington University School of Medicine, St. Louis, MO 63110.
Miletich
J P
JP
D001777:Blood Coagulation / Q000187:drug effects; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D005338:Fibrin Fibrinogen Degradation Products; D005342:Fibrinolysis / Q000187:drug effects; D005344:Fibrinopeptide A / Q000032:analysis; D005345:Fibrinopeptide B / Q000032:analysis; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D010446:Peptide Fragments / Q000032:analysis; D013300:Streptokinase / Q000494:pharmacology*; D013917:Thrombin / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; C033786:fibrinogen Bbeta (15-42); D005344:Fibrinopeptide A; D005345:Fibrinopeptide B; D006493:Heparin; D013300:Streptokinase; D013917:Thrombin; D010959:Tissue Plasminogen Activator