A Comprehensive Report on the Plasminogen-Plasmin System: From Molecular Biology to Therapeutic Intervention

1.0 Executive Summary

This report provides a comprehensive analysis of the plasminogen-plasmin system, a critical enzymatic cascade responsible for fibrinolysis and broader physiological processes including tissue remodeling and inflammation. A foundational clarification is made between plasminogen, the inactive zymogen identified by DrugBank ID DB16701 and CAS Number 9001-91-6, and its active form, plasmin, a potent serine protease. The system's central function is the degradation of fibrin clots, a process tightly regulated by a balance of physiological activators, such as tissue plasminogen activator (tPA), and inhibitors, like α2-antiplasmin. Dysregulation of this system leads to severe pathological states, including thrombosis from insufficient activity and hemorrhage from excessive activity.

Therapeutic intervention targeting this system is categorized into three distinct strategies. The most established approach involves the administration of plasminogen activators (e.g., Alteplase) for acute thrombolytic therapy in conditions like ischemic stroke and myocardial infarction. A second, more recent strategy is plasminogen replacement therapy (e.g., Ryplazim) for the chronic management of congenital plasminogen deficiency. The third is the investigational use of direct-acting plasmin, which aims to provide localized thrombolysis with a potentially improved safety profile. Across all pro-fibrinolytic therapies, hemorrhage remains the principal and mechanism-based safety concern, dictating stringent patient selection and risk management. Key knowledge gaps persist, most notably the clinical pharmacokinetics of exogenously administered plasmin. Future advancements in the field are trending towards precision medicine, focusing on developing agents with enhanced fibrin-specificity, novel delivery methods for localized effects, and curative app