Characterization of Hemostatic Disordres in Septic Shock: Searching for Biological Markers

Study Overview
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Brief Summary
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Sepsis induces hemostatic disorders due to the exessive or inappropriate activation of inflammation, which could lead either to hypercoagulability or hypocoagulability. It is currently not possible to determine the hemostatic status of a given patient. This instability of hemostatic system is not revealed by classical tests. Thus, a better characterization of hemostatic status could certainly improve patient care. This study aims at characterizing disorders of coagulation and fibrinolysis using global tests such as thrombin generation test or coagulolytic test. Furthermore, the association with biological markers of interest (such as microparticles, neutrophil elastase or histones) will be evaluated.

Official Title
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Characterization of Hemostatic Disordres in Septic Shock: Searching for Biological Markers

Conditions
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Septic Shock

Intervention / Treatment
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* Biological: blood sampling


Participation Criteria
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Eligibility Criteria
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Eligibility criteria for patients with septic schock Inclusion Criteria: septic shock (Dellinger, 2013) age >18y hospitalized patients signature of an informed consent (emergency consent) affiliation to a social security regimen Exclusion Criteria: pregnancy or breast-feeding women moribund patient oral anticoagulant therapy thrombophilia Minor patients Patients under tutelage Eligibility criteria from subject without septic shock Subject blood samples without septic shock are collected from a historical healthy volunteers cohort.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with septic shock<br> | Biological: blood sampling<br>* additional blood sampling (volume: 18 mL)<br>|
| Other: Blood samples from a historical cohort of healthy volunteers<br> | Biological: blood sampling<br>* additional blood sampling (volume: 18 mL)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in endogenous thrombin potential as assessed by thrombin generation test | thrombin generation will be measured using CAT method (fluorescence) in plasma from patients within 48 hours. Endogenous thrombin potential is defined as the area under the thrombin generation curve and will be compared with values obtained in healthy subjects | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Thrombin peak as assessed by thrombin generation test | thrombin generation will be measured using CAT method (fluorescence) in plasma from patients within 48 hours. Thrombin peak is defined as the highest thrombin concentration derived from the thrombin generation curve and will be compared with values obtained in healthy subjects. | 48 hours | 
| Changes in clot lysis time as assessed by clot lysis assay | Clot lysis assay will, be performed in plasma from patients and will be compared with those obtained in healthy subjects. | 48 hours | 
| Correlation of neutrophil elastase with changes in endogenous thrombin potential | Neutrophil elastase will be measured in plasma from patients. | 48 hours | 
| Correlation of cell-derived microparticles with changes in endogenous thrombin potential | microparticles derived from leukocytes, erythrocytes, platelets and endothelial cells will be measured in plasma from patients by flow cytometry. | 48 hours | 
| Correlation of circulating histones with changes in endogenous thrombin potential | Circulating histones will be measured in plasma from patients | 48 hours |