Assay of thrombolytic ('fibrinolytic') mixtures intended for therapeutic use.
Anthony P. Fletcher, Norma Alkjærsig, Sol Sherry
Abstract
Anthony P. Fletcher, Norma Alkjærsig, Sol Sherry
Abstract
Abstract Commercially available streptokinase-plasmin mixtures, intended for therapeutic use as thrombolytic agents, are currently standardized in terms of arbitrary units. These assay methods, individual to each manufacturer, do not permit separate quantitation of streptokinase and plasmin contained in the mixture. An immunologic method for the assay of streptokivinase, which is uninfluenced by the presence of plasmin, has been devised. By the use of this method and a caseinolytic assay for plasmin, analysis of commercial streptokinase-plasmin preparations in terms of their separate moieties has been accomplished. Striking differences in mixture composition between preparations having identical fibrinolytic potency have been shown. Furthermore, the activities of these mixtures may be specifically inhibited by plasma containing streptokinase antibody. The experimental findings suggest that current procedures used for the standardization of streptokinase-plasmin mixtures, intended for therapeutic use, are inadequate. Methods for their improvement are suggested.
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Abstract Commercially available streptokinase-plasmin mixtures, intended for therapeutic use as thrombolytic agents, are currently standardized in terms of arbitrary units. These assay methods, individual to each manufacturer, do not permit separate quantitation of streptokinase and plasmin contained in the mixture. An immunologic method for the assay of streptokivinase, which is uninfluenced by the presence of plasmin, has been devised. By the use of this method and a caseinolytic assay for plasmin, analysis of commercial streptokinase-plasmin preparations in terms of their separate moieties has been accomplished. Striking differences in mixture composition between preparations having identical fibrinolytic potency have been shown. Furthermore, the activities of these mixtures may be specifically inhibited by plasma containing streptokinase antibody. The experimental findings suggest that current procedures used for the standardization of streptokinase-plasmin mixtures, intended for therapeutic use, are inadequate. Methods for their improvement are suggested.
Key concepts: Streptokinase, Plasmin, Chemistry, Fibrinolysin, Chromatography, Pharmacology, Fibrinolytic agent, Biochemistry