Toward improved thrombolysis in ischemic stroke: targeting nonfibrin components

A State of the Art lecture titled "Targeting nonfibrin components in ischemic stroke" was presented at the International Society on Thrombosis and Haemostasis Congress in 2025. Fibrinolysis using recombinant tissue plasminogen activators remains the primary pharmacologic approach for reperfusion therapy in ischemic stroke. Its clinical benefit has been well established over the past 3 decades. However, fibrinolytic therapy is not universally effective, and its limitations have become increasingly apparent. Recent research has provided deeper insights into acute ischemic stroke thrombus composition and architecture, revealing complex structures containing not only fibrin but also cellular and extracellular components that contribute to fibrinolysis resistance. These findings have led to the development of novel strategies aimed at targeting nonfibrin components to enhance overall thrombolysis and overcome fibrinolysis resistance. This review highlighted the current evidence from studies on ischemic stroke thrombi that underpin emerging thrombolytic strategies that target nonfibrin components and discusses their potential clinical implications. Finally, relevant new data on this topic presented during the 2025 International Society on Thrombosis and Haemostasis Congress were summarized.