Lack of a rationale for the task force recommendation regarding re-administration of streptokinase.

Dear Sir In the recently published Task force report, under section ‘Fibrinolytic regimens’, the authors recommend not to readminister streptokinase for at least 10 years. The reference supporting this statement is Ref. 51. After evaluating this paper and looking into the literature my comments are as follows: The referenced publication only contains data up to 7.5 years. In so far any comment exceeding this period cannot be drawn from this publication. Squire and his cowriters performed an excellent retrospective analysis. I.e. they analyzed blood samples of patients after discharge from a hospital. Evidently they measured single antibody titers at a given period after thrombolysis, but not reported the course of such titers over time. They definitely found a decrease of titer levels over time, but interestingly in their series, patients from 12 up to 35 month did not present SK-antibodies, the authors suggest for the inhibition of thrombolytic activity. In contrast, single patients after this period presented with high titers, which the authors suggest may negatively impact thrombolytic therapy. Although the presence of Streptokinase antibodies in individual patients is an important observation, the origin of antibody elevation remains unclear and relation to a previous Streptokinase application is questionable. The absence of detectable antibodies against streptokinase in a relatively small control group is not a proof for persistence of antibodies. I refer to the publications of Fears and coworkers, which in the Team-2 trial could not detect an influence of pretreatment antibodies on efficacy of streptokinase or anistreplase. The authors also evaluated safety parameters, but could not detect any additional risks arising from a reapplication of streptokinase, when applied according to the approved package information (i.e. no readministration between 5 days and 1 year). In a second publication Fears and coworkers investigated the course of antibody titers. From their data the authors conclude that a streptokinase resistance is unlikely for 92% of the population after 12 months and 100% after 18 months after first application. Slightly elevated SK antibody titers are not preventive with regard to streptokinase efficacy. In the discussion the authors conclude as follows: ‘Our results suggest that much of a second dose of SK might be neutralized up to six months after the first dose but not at 12 months’. In conclusion, I recommend changing the respective paragraph of the Task Force publication. In my opinion, data for such a recommendation are inappropriate and definitely not supported by the reference. This view is further supported by the streptokinase antibody titer courses reported from the Terima investigators. My concern with the recommendation as mentioned is, that a large number of patients who still have a benefit after the first streptokinase application will be withhold from efficient therapy.