Fibrin Network Formation and Lysis in Septic Shock Patients.

Julie Brogaard Larsen,Anne-Mette Hvas,Christine Lodberg Hvas,Kim Michael Larsen,Mathies Appel Aggerbeck

doi:10.3390/ijms22179540

Julie Brogaard Larsen, Anne-Mette Hvas + Show 3 more

Open Access

https://doi.org/10.3390/ijms22179540

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Abstract

Background: 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. Methods: 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. Results: 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). Conclusion: 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.

Highlights

Septic shock patients are at high risk of developing coagulation disturbances, which, in their most severe form, may manifest as disseminated intravascular coagulation (DIC), a life-threatening condition [1,2]
Altered fibrinolysis is recognised as a contributor to sepsis-related coagulopathy and may aggravate microthrombus formation, organ failure and mortality [3,4,5]
The present study was a post-hoc study to a prospective cohort study including adult septic shock patients admitted to the intensive care unit (ICU) [13]

Summary

Introduction

Septic shock patients are at high risk of developing coagulation disturbances, which, in their most severe form, may manifest as disseminated intravascular coagulation (DIC), a life-threatening condition [1,2]. Sepsis patients are generally considered to have impaired fibrinolysis [3,4]; recent literature indicates that some patients with sepsis-related DIC have decreased fibrin formation capacity [6] and even enhanced clot susceptibility to lysis [7], and hypocoagulability in sepsis has been associated with poor prognosis [8] This may hold new implications for the treatment of coagulation disturbances in sepsis, as patients with decreased fibrin formation capacity or increased lysis could benefit from antifibrinolytics in the case of active bleeding or the need for invasive procedures. 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.

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