A study in 25 patients who had been given streptokinase for treatment of acute myocardial infarction, found that 12 weeks later, 24 patients had enough anti-streptokinase antibodies in circulation to neutralise an entire
1.5 million unit dose of streptokinase. After 4 to 8 months,18 out of 20 still had enough antibodies to neutralise half of a 1.5 million unit dose of streptokinase (See reference number 1). Further study has suggested that after streptokinase use,anti-streptokinase antibodies fall within 24 hours, but then increase gradually and are significantly raised by 4 days after treatment. The antibody titres reach a peak (approximately 200 times that of pretreatment levels) after 2 weeks and then subsequently decline,but remain above baseline values for at least one year (See reference number 2). Antibody titres may remain high enough to neutralise effects of streptokinase for several years after a dose,(See reference number 3,4) and high titres persisting for up to 7.5 years have been reported (See reference number 5). However, in contrast, another study found that neutralising antibody titres had returned to control levels by 2 years (See reference number 6). Increased titres of streptokinase antibodies have also been seen in patients receiving topical streptokinase for wound care,(See reference number 7)intrapleural streptokinase for pleural effusions,(See reference number 8) and following streptococcal infections (See reference number 9). Apart from reduced thrombolytic effect, repeated dosing(See reference number 10) or high pre-treatment anti-streptokinase antibody titres(See reference number 11) may increase risk of allergic reactions.
Anistreplase,like its parent drug streptokinase, has been shown to be neutralised by anti-streptokinase antibodies (See reference number 12,13).
Of 6 patients given urokinase 1.5 million units infused over 30 minutes for recurrent myocardial infarction,rigors occurred in 4 patients and 2 of these also had bronchospasm; they had all previously received streptokinase (See reference number 14).
Streptokinase use causes production of anti-streptokinase antibodies. These persist in circulation so that clot-dissolving effects of another dose of streptokinase given many months later may be ineffective, or less effective, because it becomes bound and neutralised by antibodies. Many people already have a very low titre of antibodies resulting from previous streptococcal infections,yet this does not usually appear to influence thrombolysis (See reference number 15).
The interaction that results in neutralisation of thrombolytics is established and clinically important. One author(See reference number 16)says that clinically,therapy is not repeated within a year as it would not work. Given that it has been suggested that effects may be very persistent, it would seem prudent, if a second use is needed, to use a thrombolytic with less antigenic effects such as alteplase. The British National Formulary says that streptokinase should not be used again beyond 4 days of first use of either streptokinase or anistreplase (See reference number 17). In addition, manufacturer recommends avoidance of streptokinase in patients who have had recent streptococcal infections that have produced high anti-streptokinase titres, such as acute rheumatic fever or acute glomerulonephritis (See reference number 9).
Little is known about increased risk of hypersensitivity reactions
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