NEUTRALIZING ANTIBODIES TO STREPTOKINASE 4 YEARS AFTER INTRAVENOUS THROMBOLYTIC THERAPY

Neutralization antibodies to streptokinase increase to high levels within several days of administration. It is not known how long these high levels persist. The time course of antibody levels needs to be further characterized owing to the increasing need to readminister thrombolytic therapy, and to the possibility that these antibodies may compromise the safety and efficacy of a further dose of streptokinase or streptokinase-containing compounds. In this study, paired streptokinase neutralization titers (in vitro functional assay) and specific antistreptokinase immunoglobulin G (IgG) antibody levels were measured in 145 patients who received streptokinase between 10 and 48 months previously. Serologic evidence of recent streptococcal infection was also sought. Neutralization titers sufficient to inactivate a conventional dose of 1,500,000 units of streptokinase were still present in 50% of patients (95% confidence interval 36-64) at 24 months, 48% (34-62) at 36 months, and 51% (37-71) at 48 months after streptokinase administration. Levels of specific antistreptokinase IgG antibodies also remained constant over the 1- to 4-year period. Neutralization titers were weakly correlated with specific IgG levels (r = 0.35). Antistreptolysin titers greater-than-or-equal-to 250 and greater-than-or-equal-to 333 IU/ml were present in 30% (24-38) and 12% (8-18) of these patients, respectively. Neutralization titers were not correlated with antistreptolysin titers. Neutralizing antibodies (assessed by an in vitro functional assay) remained high in 51% of patients 4 years after intravenous streptokinase administration. It is not known whether persisting high in vitro neutralization titers affect the efficacy and safety of repeat administration of streptokinase or streptokinase containing compounds.