Staphylokinase: A Comprehensive Review of its Thrombolytic Potential, Clinical Development, and Future Prospects

Introduction: The Evolving Landscape of Thrombolytic Therapy

Thrombotic diseases, including acute myocardial infarction (AMI), ischemic stroke, deep vein thrombosis (DVT), and pulmonary embolism (PE), represent a leading cause of mortality and morbidity worldwide, imposing a substantial burden on global health systems.[1] The cornerstone of treatment for these acute conditions is the rapid dissolution of the occlusive thrombus to restore blood flow, a strategy known as thrombolytic therapy. The development of plasminogen activators—agents that convert the zymogen plasminogen into the active fibrin-degrading enzyme plasmin—has revolutionized the management of these life-threatening events.[1]

The field has seen successive generations of thrombolytic agents, from the non-fibrin-specific first-generation drugs like streptokinase and urokinase to the more fibrin-specific second-generation agent, recombinant tissue-type plasminogen activator (t-PA, alteplase).[1] Despite these advances, the ideal thrombolytic agent remains elusive, with existing therapies facing limitations related to bleeding risk, incomplete efficacy, reocclusion, and cost.[3]

In this context, staphylokinase (SAK) emerged as a highly promising third-generation thrombolytic agent.[3] Staphylokinase is a 136-amino acid, non-glycosylated protein secreted by certain lysogenic strains of

Staphylococcus aureus.[6] Unlike direct-acting proteases, SAK is a profibrinolytic agent that exhibits a unique mechanism of plasminogen activation, conferring a high degree of fibrin-specificity that distinguishes it from its predecessors.[11]