Rationale Fibrinolysis resistance in sepsis associates with thrombotic burden, multi-organ failure and death. The degrees and dynamics of resistance that associate with mortality in acute sepsis are unknown, and a simple tool to aid clinician interpretation of fibrinolysis measurements is lacking.

Objectives To establish a point of care grading tool of fibrinolysis resistance that aligns with scoring systems for disease acuity, is substantiated by plasma fibrinolysis markers and enables rapid investigation of the fibrinolysis state at the point of care.

Methods Prospective observational study of 116 adult sepsis/septic shock patients with sequential measurements of fibrinolysis resistance during Intensive Care Unit (ICU) admission using tissue plasminogen activator (tPA) enhanced viscoelastic testing (VET). The clot lysis time (TPA-LT) adjusted for fibrin clot amplitude (TPA-LT/FIBA10, sec/mm) underwent cluster analysis and was evaluated against disease severity scores, standard pathology, clinical outcomes and fibrinolysis markers.

Measurements and Main Results Three clusters of progressively increasing fibrinolysis resistance were identified (Grades 1-3). At admission, Grade 3 associated with the highest disease severity, organ failure, haematological and biochemical perturbations, fibrinolysis marker inhibitory profile and mortality (42% versus 24% and 15% in Grade 2 and Grade 1, respectively) with a 3.9-fold [95% CI 1.4-11] increased hazard ratio for death at 28 days compared to Grade 1. Transitions between grades were frequent over 7 days with a reduced Grade associated with decreased risk of death.

Conclusions Grading of fibrinolysis resistance in sepsis enables rapid identification of patients at greatest mortality risk with any dynamic improvement corresponding to favourable clinical outcomes.

The authors have declared no competing interest.

This study received departmental funding only

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

South Western Sydney Local Health District Human Research Ethics Committee (2022/ETH02122). Consent was waived as permitted under the National Statement on Ethical Conduct in Human Research 2023 for low risk research in critically ill patients.

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Support: This study was funded by the Liverpool Hospital Intensive Care Research Fund and by a National Health and Medical Research Council of Australia Ideas grant (RG231458, CIA Coupland).

Data Sharing Statement: Data interaction app links provided in manuscript

For original data, please contact corresponding authors.