Fibrin Network Formation and Lysis in Septic Shock Patients

Septic shock patients are prone to altered fibrinolysis, which contributes to microthrombus formation, organ failure and mortality. However, characterisation of the individual patient's fibrinolytic capacity remains a challenge due to a lack of global fibrinolysis biomarkers. We aimed to assess fibrinolysis in septic shock patients using a plasma-based fibrin clot formation and lysis (clot-lysis) assay and investigate the association between clot-lysis parameters and other haemostatic markers, organ dysfunction and mortality.

This was a prospective cohort study including adult septic shock patients (n = 34). Clot-lysis was assessed using our plasma-based in-house assay. Platelet count, activated partial thromboplastin time (aPTT), international normalised ratio (INR), fibrinogen, fibrin D-dimer, antithrombin, thrombin generation, circulating fibrinolysis markers and organ dysfunction markers were analysed. Disseminated intravascular coagulation score, Sequential Organ Failure Assessment (SOFA) score and 30-day mortality were registered.

Three distinct clot-lysis profiles emerged in the patients: (1) severely decreased fibrin formation (flat clot-lysis curve), (2) normal fibrin formation and lysis and (3) pronounced lysis resistance. Patients with abnormal curves had lower platelet counts (p = 0.05), more prolonged aPTT (p = 0.04), higher lactate (p < 0.01) and a tendency towards higher SOFA scores (p = 0.09) than patients with normal clot-lysis curves. Fibrinogen and fibrin D-dimer were not associated with clot-lysis profile (p ≥ 0.37).

Septic shock patients showed distinct and abnormal clot-lysis profiles that were associated with markers of coagulation and organ dysfunction. Our results provide important new insights into sepsis-related fibrinolysis disturbances and support the importance of assessing fibrinolytic capacity in septic shock.