Point Of Care Evaluation of Fibrinolysis In Sepsis: The POCEFIS study

Abstract Purpose: Sepsis-induced coagulopathy (SIC) involves a complex imbalance between coagulation activation and fibrinolysis inhibition, contributing to microvascular thrombosis and organ dysfunction. Conventional coagulation tests inadequately capture functional fibrinolytic alterations. The POCEFIS study used the ClotPro® tissue plasminogen activator (TPA) test to characterize fibrinolysis in septic patients and evaluate its clinical relevance and temporal evolution during the early phase of sepsis. Methods: In a cohort of septic intensive care unit (ICU) patients, fibrinolysis was assessed using the ClotPro® TPA-test at enrollment and on day 1, 2, 3 and 7 after enrollment. Specific plasma biomarkers (PAI-1, plasminogen, protein C, and protein S) were analyzed at enrollment and on day 2 and 7. Septic patients were classified according to temporal evolution of fibrinolytic status during the first three days of observation (normal versus impaired fibrinolysis). Results: At enrollment, impaired fibrinolysis was present in 38% of septic patients. However, considering the first three ICU days, 66% of patients exhibited fibrinolysis impairment. Impaired fibrinolysis was associated with higher lactate (4.2 mmol/L vs 2.9 mmol/L, p=0.0482), INR (1.5 vs 1.2, p=0.0156), and SOFA score (10.9 vs. 9.4, p=0.0282) at enrollment. Patients with impaired fibrinolysis showed persistently higher C-reactive protein and D-dimer values during the first week of observation (linear mixed-effects model, group effect p=0.0047 and p=0.0201). Conclusions: Fibrinolysis impairment is frequent, dynamic, and clinically relevant in sepsis. The ClotPro® TPA-test provides a global point-of-care evaluation of fibrinolysis. Serial viscoelastic assessment may improve risk stratification and support the development of individualized therapeutic strategies targeting SIC.