Pro-inflammatory Role of Blood Platelets in Critically Ill Patients With Septic Shock.

Pro-inflammatory Role of Blood Platelets in Critically Ill Patients With Septic Shock: an Observational Study.

Blood platelets play a major role in the inflammatory response. A dysregulation of platelets activation may be one of the contributors to tissue damage in critically ill patients with septic shock. The main objective of this study is to compare platelet activation markers levels (including plasma concentration in CD154, beta thromboglobulin, platelet factor 4, platelet microparticles, soluble CD62, RANTES, GRO-alpha and HMGB-1) at the early phase of a septic shock and a systemic inflammatory response syndrome (SIRS).

Sepsis is defined as life-threatening organ dysfunction due to dysregulated host response to infection which can lead to many failures of vital organs (kidneys, lungs, liver) in critically ill patients. It is accompanied at an early phase by both a proinflammatory and procoagulant state generating many platelet activators. Given their essential role in the inflammatory response, a dysregulation of platelets activation may be one of the contributors to tissue damage. To determine if platelet activation contribute to deregulation of the inflammatory response of the host in sepsis, the main objective of this study is to compare platelet activation markers levels of patients with septic shock and after major surgery. Plasma concentration in CD154, beta thromboglobulin, platelet factor 4, platelet microparticles, soluble CD62, RANTES, GRO-alpha, HMGB-1, monocyte Dnases signal, circulating free DNA and DNase1 and DNase1L3 activities will be studied and compared at inclusion (Day 0), Day 1 and Day 5.

Inclusion Criteria:

• Patients aged over 18 years admitted to an intensive care unit for:

  • a septic shock evolving for less than 24h (defined by an increase in the SOFA (Sequential Organ Failure Assessment) score of at least 2 points related to an infection, a persisting hypotension requiring vasopressors to maintain MAP ≥65 mmHg and a serum lactate level >2 mmol/L (18 mg/dL) despite adequate volume resuscitation)
  • Or a systemic inflammatory response syndrome (SIRS) evolving for less than 24h (defined as 2 or more of the following variables: fever of more than 38°C or less than 36°C, heart rate of more than 90 beats per minute, respiratory rate of more than 20 breaths per minute or arterial carbon dioxide tension (PaCO2) of less than 32 mm Hg, abnormal white blood cell count (>12,000/µL or <4,000/µL or >10% immature forms).

Exclusion Criteria:

• Age < 18 years
• Known history of constitutional thrombopathy (Bernard Soulier's disease, Glanzmann thrombasthenia, Gray's syndrome or dense granule disease)
• Myeloproliferative or myelodysplastic syndrome
• Autoimmune thrombocytopenic purpura
• Acute leukemia
• Haemorrhagic shock
• Platelet transfusion within 7 days prior to inclusion
• Antiplatelet medication (clopidogrel or ticagrelor taken within 5 days of inclusion, prasugrel or dipyridamole within 7 days of inclusion)
• Active HIV infection or known active hepatitis B or C
• Pregnant or breastfeeding woman
• Patients protected by the law, under guardianship or trusteeship, or deprived of liberty
• Patients without health insurance