Evaluation of a standard dosage schedule with streptokinase.

T HE FEASIBILITY of producing dissolution of thrombi by enzymatic means has been demonstrated in experimental thrombi and pulmonary emboli in animals, in experimental venous thrombi in man6 and in patients with acute venous and arterial thromboembolic disease.7 8 Of the enzymes investigated, only the two plasminogen activators, streptokinase and urokinase, have proved acceptable as thrombolytic agents for clinical use.19 Streptokinase is now available in a highly purified form but has the disadvantage of being antigenic to man. Pyrogenicity, formerly a major difficulty with the earlier preparations,19’2#{176} is no longer a serious problem if prophylactic corticosteroids are used. Streptokinase has the advantage of being considerably less expensive than urokinase and is more readily available ; however, urokinase has the advantage of being nonantigenic. The problems associated with the antigenicity of streptokinase are manifest in two ways. The first is due to the fact that streptococcal antibodies cross-react with streptokinase. These antilx)dies, the result of previous streptococcal infections, are present in most patients and must be neutralized before thrombolysis can be produced.21 The streptococcal antibodies combine with, and inactivate streptokinase, and the streptokinase-antibody complex thus formed is then rapidly cleared from the bloodstream.22 The neutralizing dose of streptokinase cannot be predicted with any certainty because the concentration of streptococcal antibodies varies over a wide range from patient to patient.21 For this reason a streptokinase resistance test is usually performed on every patient before commencing treatment. The second problem arising from the antigenicity of streptokinase is that treatment causes a marked increase in the level of streptokinase antibodies, and this precludes further therapy should this be necessary in the next one to six months.21’23 The principles of thrombolytic therapy with streptokinase, and more recently, urokinase, have been established by the important fundamental and clinical investigations of Fletcher, Sherry and Alkjaersig.2125 Streptokinase produces its