Utility of fibrinolysis enhanced viscoelastic assays to evaluate fibrinolysis disorders in critically ill adults with severe infection: a scoping review.

Background: Acutely infected critically ill patients develop coagulopathies and perturbations to the fibrinolysis system that manifest as immunothrombosis. Whole blood viscoelastic testing, using an exogenous fibrinolytic agent to enhance fibrinolysis (FE-VET) can assess both processes of coagulation and fibrinolysis at the bedside. This scoping review aimed to illustrate clinical applicability, knowledge gaps and unmet needs for this emerging technology.

Methods: A systematic search of bibliographic databases and the grey literature was performed between the 10th October 2024 and the 14th January 2025 using a pre-published protocol and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline for scoping reviews (PRISMA-ScR). Studies reporting FE-VET to investigate fibrinolysis in acutely infected patients admitted to the intensive care unit were assessed, including associations with disease severity and clinical outcomes.

Results: The search identified 297 studies with 24 included in this review. Fifteen studies were observational (12 prospective, 3 retrospective), 4 case reports and series, 2 validation studies, 2 letters, and 1 poster abstract. No randomised controlled trials were identified. Most studies used varying concentrations of tissue plasminogen activator (tPA) to enhance fibrinolysis, with FE-VET performed at a single time point and the lysis time to achieve 50% reduction of maximum clot firmness being the most frequently reported variable. Fibrinolysis resistance was the prevailing state reported in acute sepsis or COVID-19 infections and associated with increased disease severity and worse clinical outcomes.

Conclusion: Viscoelastic testing using a fibrinolysis enhancing agent demonstrated a spectrum of fibrinolysis resistance in acutely infected critically ill patients, associated with increased disease severity and mortality. Standardisation of the concentrations of fibrinolysis enhancing agents and the reporting of clot lysis parameters across testing devices are needed to establish reference values. This would improve future clinical studies of fibrinolysis, including trials of fibrinolytic therapies using a personalised medicine approach.