Comparative immunogenicity and thrombolytic properties toward arterial and venous thrombi of streptokinase and recombinant staphylokinase in baboons

• Published in: Circulation (New York, N.Y.) N.Y.), 1993-03, Vol.87 (3), p.996-1006
• Main Authors: COLLEN, D, DE COCK, F, STASSEN, J.-M
• Format: Article
• Language: English
• Subjects: Animals; Aspirin - pharmacology; Biological and medical sciences; Bleeding Time; Blood. Blood coagulation. Reticuloendothelial system; Femoral Artery; Femoral Vein; Fibrinolytic Agents - pharmacology; Heparin - pharmacology; Humans; Jugular Veins; Medical sciences; Metalloendopeptidases - blood; Metalloendopeptidases - pharmacology; Neutralization Tests; Papio; Pharmacology. Drug treatments; Plasma - physiology; Recombinant Proteins; Streptokinase - antagonists & inhibitors; Streptokinase - immunology; Streptokinase - pharmacology; Thrombosis - blood
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.87.3.996

Streptokinase is a routinely used thrombolytic agent that is immunogenic and relatively inefficient toward platelet-rich thrombus, whereas staphylokinase is a poorly studied fibrinolytic agent. Here, the comparative immunogenicity and thrombolytic properties toward arterial platelet-rich thrombus and venous whole blood clots of streptokinase and recombinant staphylokinase were studied in baboons. The inhibitory capacity of baboon plasma (in a human plasma-based clot lysis assay) was 0.39 +/- 0.25 microgram streptokinase and 0.04 +/- 0.05 microgram recombinant staphylokinase per milliliter of plasma (mean +/- SD, n = 9). Intravenous infusion over 1 hour of 0.300 mg/kg of streptokinase at 0, 1, 2, 3, and 5 weeks in five baboons given heparin and the antiplatelet agent ridogrel increased the streptokinase-neutralizing titer from 0.22 +/- 0.18 microgram/mL plasma at baseline to 3.8 +/- 4.4 micrograms/mL after 2 weeks (p = 0.043 versus baseline by Wilcoxon signed rank test) and to 4.4 +/- 4.6 micrograms/mL after 5 weeks, whereas the thrombolytic potency toward a 125I-fibrin-labeled plasma clot inserted into an extracorporeal arteriovenous loop was reduced from 84 +/- 7% at baseline to 45 +/- 8% after 2 weeks and to 36 +/- 8% after 5 weeks (p < 0.01 versus baseline). Administration over 1 hour of 0.065 mg/kg recombinant staphylokinase at 0, 1, 2, 3, and 5 weeks in four baboons did not induce measurable staphylokinase-neutralizing activity in three of the four animals after 5 weeks. In the fourth baboon, a staphylokinase-neutralizing activity of 0.8 and 1.5 micrograms/mL was found at 3 and 5 weeks, respectively. Repeated staphylokinase administration was not associated with inhibition of clot lysis (43 +/- 4% lysis at baseline, 52 +/- 9% at 3 weeks, and 61 +/- 14% at 5 weeks; p = NS versus baseline). Repeated administration of streptokinase but not of staphylokinase caused a marked (> 50%) decrease in blood pressure, requiring administration of steroids and intravenous fluids, and a marked increase in leukocyte count and hemoglobin concentration. Intravenous infusion of streptokinase or recombinant staphylokinase over 1 hour in doses ranging between 0 and 1.0 mg/kg in three groups of four baboons each induced dose-dependent lysis of a 125I-fibrin-labeled autologous jugular vein blood clot (50% lysis requiring 0.140 mg/kg streptokinase and 0.058 mg/kg recombinant staphylokinase, representing equimolar amounts of 3.25 nmol/kg) without systemic fibrinogen depletion.