The Procoagulant and Fibrinolytic Balance of Microvesicles Predicts Mortality in Septic Shock Patients

R. Lacroix^1,2, C. Judicone³, K. Harti Souab², A. Loundou⁴, T. Bouriche³, S. Cointe^1,2, L. Vallier¹, A. Bonifay¹, E. Abdili², L. Arnaud², S. Robert¹, P. Poncelet³, C. Grosdidier², P. Morange^1,2, J.-C. Gris⁵, J.-Y. Lefrant⁵, E. Cochery-Nouvellon⁵, M. Leone², J. Albanese², F. Dignat-George^1,2

¹C2VN, INSERM, Aix-Marseille University, Marseille, France, ²Assistance Publique Hôpitaux de Marseille (AP-HM), Marseille, France, ³BioCytex, Marseille, France, ⁴CEReSS, Aix-Marseille University, Marseille, France, ⁵CHU Nîmes, Univ Montpellier, Nîmes, France

Abstract Number: OC 71.3

Meeting: ISTH 2021 Congress

Theme: Coagulation and Natural Anticoagulants » Microparticles

Background: Septic shock (SS) is characterized by an abnormal coagulation activation with defective fibrinolysis, leading to a high mortality rate. The cellular activation associated with the production of microvesicles (MV) by blood and vascular cells. Initially described as procoagulant and proinflammatory. MV have been more recently ascribed a fibrinolytic activity suggesting the existence of compensating mechanisms which may counteract their deleterious activity in SS patients.

Aims: Therefore, we investigated whether the balance between the procoagulant and fibrinolytic activities of MV defined as the MV-coagulo-fibrinolytic balance (MV-CLB) predicts mortality in SS patients.

Methods: SS patients (n=225) were included in a multi-center prospective study. Informed consent was obtained and the study was approved by an ethics committee. MV-CLB was quantified as a ratio (arbitrary units; a.u.) between the procoagulant activity of MV measured by a highly sensitive TF-dependent factor Xa generation assay and their fibrinolytic activity measured by an immuno-magnetic separation-based plasmin generation assay. Links between MV-CLB and clinical and biological severity markers were investigated.

Results: The mortality rate at day 90 was 25.2%. Patients who died showed a significantly higher MV-CLB compared to patients who survived (2.19 [0.61-13.8] a.u. vs 0.78 [0.25-1.73] a.u., p<0.001) at inclusion. This result was confirmed on repeated samples at 24h and 48h. Interestingly, MV-CLB was a better predictor than the procoagulant and profibrinolytic activities taken individually. Cox regression analysis showed that MV-CLB was an independent predictor of mortality (Hazard Ratio = 1.02 CI [1.01-1.04], p=0.002) and allowed to stratify SS patients in low (<10%), medium (22%) and high risk (>40%) of mortality. The MV-CLB correlates with the severity simplified acute physiology score (SAPS-II) (r²=0.27) and hypoxia marker (lactates, r²=0.22).

Conclusions: This study demonstrates that MV-CLB is an independent prognosis factor in SS. This new functional signature of MV opens promising avenues for the guidance of individualized therapy targeting coagulopathy in SS.

To cite this abstract in AMA style:

Lacroix R, Judicone C, Harti Souab K, Loundou A, Bouriche T, Cointe S, Vallier L, Bonifay A, Abdili E, Arnaud L, Robert S, Poncelet P, Grosdidier C, Morange P, Gris J-, Lefrant J-, Cochery-Nouvellon E, Leone M, Albanese J, Dignat-George F. The Procoagulant and Fibrinolytic Balance of Microvesicles Predicts Mortality in Septic Shock Patients [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/the-procoagulant-and-fibrinolytic-balance-of-microvesicles-predicts-mortality-in-septic-shock-patients/. Accessed November 29, 2023.

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