title: Procoagulant properties of intravenous staphylokinase versus tissue-type plasminogen activator.
abstract: The fibrin-specificity and procoagulant effects of recombinant staphylokinase (Sak42D) were compared with those of recombinant tissue-type plasminogen activator (rt-PA) in patients with acute myocardial infarction. Plasma samples were obtained at baseline and at 25 and 90 min, from 24 patients who were randomly assigned to a double bolus (15 mg each, 30 min apart) administration of Sak42D or to accelerated weight-adjusted rt-PA (maximum of 100 mg over 90 min). Baseline levels of fibrinopeptide A (FPA), prothrombin fragment 1 + 2 and thrombin-antithrombin III complex (TAT) were comparable in the Sak42D and rt-PA groups (p > or = 0.6). In patients treated with Sak42D, plasma levels of FPA, prothrombin fragment 1 + 2 and TAT did not markedly increase during treatment (p = 0.06, p = 0.4 and p = 0.03, respectively). In contrast, during administration of rt-PA the levels of FPA, prothrombin fragment 1 + 2 and TAT increased significantly over baseline (p = 0.003, p < 0.0001 and p = 0.001, respectively). As a result, the levels of all three procoagulant parameters were significantly lower during treatment with Sak42D as compared to rt-PA. Thus, FPA levels in the Sak42D group (median values) were 40 ng/ml at 25 min and 11 ng/ml at 90 min, as compared to 88 ng/ml and 50 ng/ml in the rt-PA group (p = 0.0007 and p = 0.009, respectively). Prothrombin fragment 1 + 2 levels in the Sak42D group were 1.3 nM at 25 min and 1.2 nM at 20 min, as compared to 11 nM and 5.3 nM in the rt-PA group (both p < 0.0001). TAT levels were 4.7 ng/ml at 25 min and 6.2 ng/ml at 90 min in the Sak42D group, with corresponding values of 16 ng/ml and 9.6 ng/ml in the rt-PA group (p = 0.02 and p = 0.03, respectively). In the patients treated with Sak42D, no significant systemic fibrinolytic activation was observed, as revealed by unaltered levels of clottable fibrinogen, plasminogen and alpha 2-antiplasmin up to 90 min after the start of therapy. In contrast, the corresponding residual levels at 90 min in patients treated with rt-PA decreased to (mean +/- SEM; n = 12) 62 +/- 6%, 45 +/- 5% and 52 +/- 10%, respectively (all p < or = 0.01 versus the Sak42D group). These data confirm the high degree of fibrin-specificity of Sak42D and demonstrate that this is associated with significantly less generation of procoagulant activity in plasma after intravenous administration in patients with acute myocardial infarction.
authors.affiliation: Center for Molecular and Vascular Biology, University of Leuven, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Okada
authors.forename: H R
authors.initials: HR
authors.lastname: Lijnen
authors.forename: H
authors.initials: H
authors.lastname: Moreau
authors.forename: S
authors.initials: S
authors.lastname: Vanderschueren
authors.forename: D
authors.initials: D
authors.lastname: Collen
mesh_terms: D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D008666:Metalloendopeptidases / Q000008:administration & dosage*; D009203:Myocardial Infarction / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus