The Fibrinolytic System in Bacterial Sepsis: A Comprehensive Review of Current Assessment Methods

Background: Fibrinolytic impairment is one of the key factors involved in the pathogenesis of hemostasis disturbances in sepsis, significantly contributing to microthrombosis, organ dysfunction, and mortality rates. While hemostatic assessment in sepsis typically focuses on coagulation activation, evaluating fibrinolytic activity remains challenging due to methodological limitations and a lack of standardization of the currently available methods. Objectives: This comprehensive review examines current methods for assessing fibrinolytic activity in bacterial sepsis, their clinical applications, strengths and limitations, and future perspectives for improved diagnostic approaches. Methods: We conducted a systematic literature search and identified 52 studies that investigated fibrinolysis assessment in adult patients with bacterial sepsis using biomarkers or global tests. Studies included mainly observational cohorts examining various fibrinolytic assessment methods. Results: Fibrinolytic shutdown, primarily mediated by the overproduction of plasminogen activator inhibitor-1 (PAI-1), occurs early in sepsis and correlates with disease severity and mortality. Current assessment methods include plasma biomarker measurements (PAI-1, plasmin-antiplasmin complexes, D-dimer), global plasma-based tests (clot lysis time, plasmin generation assays), and whole-blood viscoelastic testing (rotational thromboelastometry, ROTEM; thromboelastography, TEG). Modified viscoelastic tests incorporating tissue plasminogen activators demonstrate enhanced sensitivity for detecting fibrinolytic resistance. Despite efforts, standardization is still limited, and routine clinical implementation has not been achieved yet. Conclusions: Fibrinolytic assessment provides important prognostic information in sepsis, despite methodological challenges. The integration of point-of-care viscoelastic testing with modified protocols shows promise for real-time evaluation. Future research should focus on developing standardized, automated assays suitable for routine clinical practice, enabling personalized therapeutic interventions that target fibrinolytic dysfunction in sepsis.