Evaluation of the Global Fibrinolytic Capacity of Whole Blood

Abstract

Abstract Assessment of the global fibrinolytic capacity of whole blood is of great clinical value for the diagnosis of bleeding and thrombotic disorders, the guidance of therapeutic decision-making, and prognosis monitoring. However, due to the complexity of the fibrinolytic system, existing fibrinolysis assays fail to meet clinical diagnostic requirements, and it remains challenging to design a “gold standard” analytical method that can reflect the global fibrinolysis level of blood. Here, we constructed a fibrin clot exhibiting optical interference effects as a fibrinolysis model, and introduced an ordered porous layer interferometry (OPLI) technique for real-time, in situ monitoring of the global fibrinolytic capacity of whole blood. We equated the global fibrinolytic capacity to plasmin activity while effectively suppressing non-specific adsorption under dynamic blood-flow conditions, thereby enabling accurate quantitative evaluation. The developed method was applied to monitor the dose-dependent downregulating effects of the endogenous fibrinolytic inhibitors PAI-1 and α2-AP on whole blood global fibrinolytic activity. Furthermore, this method successfully differentiated and quantified the ranges of global fibrinolytic capacity among hypofibrinolysis, normal fibrinolysis, and hyperfibrinolysis phenotypes. The analytical results showed a strong correlation with corresponding clinical bleeding and thrombosis risk scores. A parallel comparison with the thromboelastography method further validated the clinical applicability of this method.