Exploration of tissue injury mechanisms in Sepsis in patients with Febrile Neutropenia

• Grant number: 21/12945-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): May 01, 2022
• Effective date (End): April 30, 2024
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Erich Vinicius de Paula
• Grantee: Letícia Queiroz da Silva Justo
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 16/14172-6 - Investigation of the pathophysiological aspects and novel therapeutic approaches for thromboembolic disorders, AP.TEM

Abstract

Febrile Neutropenia (NF) is a serious complication of antineoplastic chemotherapy, particularly in hematologic patients. Among the most feared complications of NF are Sepsis and septic shock. Despite advances in supportive therapy, the understanding of Sepsis pathophysiology remains incomplete, limiting the development of target-specific therapies. Studies in animal models and biomarkers suggest that neutrophils and platelets act as intermediaries of tissue damage in Sepsis, particularly in the formation of NETs, which raises the question of what are the mechanisms of tissue damage in patients with severe Neutropenia and thrombocytopenia, in some cases close to zero. Thus, this project aims to explore the cellular and molecular mechanisms of tissue damage in Sepsis and septic shock in patients with NF. For this purpose, we propose a comparative analysis of the profile of tissue injury and immunothrombosis biomarkers in patients with Sepsis with severe Neutropenia and thrombocytopenia, or without changes in these counts. In addition, due to the complexity of this process, we also propose an exploratory step based on proteomics, which in other complex contexts such as Sepsis itself, has already shown the capacity of identifying new pathways of biological relevance. (AU)