PB1361 - Evaluation of the immunothrombotic response mediated by extracellular vesicles during sepsis in patients with extremely low neutrophil and platelet counts

Tuesday, June 25, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Co-Author(s)

Letícia Queiroz da Silva, Doctor of Medical Science

Postdoctoral researcher
Centro de Hematologia e Hemoterapia - Universidade de Campinas (UNICAMP), Campinas, SP, Brasil
Campinas, Sao Paulo, Brazil

Co-Author(s)

SH

Stephany Cares Huber

Biologist
Centro de Hematologia e Hemoterapia - Universidade de Campinas (UNICAMP), Campinas, SP, Brasil
Campinas, Sao Paulo, Brazil
Silmara A. De Lima-Montalvão

Biologist
Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
Campinas, Sao Paulo, Brazil
Ivanio Teixeira Borba-Junior

PhD student
Centro de Hematologia e Hemoterapia - Universidade de Campinas (UNICAMP), Campinas, SP, Brasil
Campinas, Sao Paulo, Brazil
BM

Beatriz Martinelli

Biologist
Centro de Hematologia e Hemoterapia - Universidade de Campinas (UNICAMP), Campinas, SP, Brasil
Campinas, Sao Paulo, Brazil
EA

Edilson Andrade

Nurse
Faculdade de Ciências Médicas - Universidade de Campinas (UNICAMP), Campinas, SP Brasil
Campinas, Sao Paulo, Brazil
BD

Bruno Duarte

Supervisor of the Hematology Ward
Faculdade de Ciências Médicas - Universidade de Campinas (UNICAMP), Campinas, SP Brasil
Campinas, Sao Paulo, Brazil
MC

Marcos Colella

Supervisor of the Blood Marrow Transplantation Ward
Faculdade de Ciências Médicas - Universidade de Campinas (UNICAMP), Campinas, SP Brasil
Campinas, Sao Paulo, Brazil
JA

Joyce Annichino-Bizzachi

Supervisor of the Hemostasis laboratory
Centro de Hematologia e Hemoterapia - Universidade de Campinas (UNICAMP), Campinas, SP, Brasil
Campinas, Sao Paulo, Brazil

Presenting Author(s)

Erich V. De Paula, MD, PhD

Associate Professor
University of Campinas (UNICAMP)
Campinas, Sao Paulo, Brazil

Background: Sepsis arises from a host-dysregulated response to pathogens causing tissue damage at least partially due to activation of hemostasis in a process termed immunothrombosis, in which neutrophils, platelets, and extracellular vesicles (EVs) play critical roles. Interestingly, individuals with hematological malignancies experiencing chemotherapy-induced febrile neutropenia (FN) with neutrophil and platelet counts close to zero, also manifest sepsis and extensive organ damage, whose mechanisms have not been elucidated yet.

Aims: To explore the contribution of EVs to the pathogenesis of immunothrombosis and sepsis in febrile neutropenia patients

Methods: The study enrolled patients with hematologic malignancies chemotherapy-induced neutropenia ( < 500/μl) and fever. Samples were obtained at fever, at sepsis onset, and 72 hours thereafter. Clinical, laboratory, and sepsis outcomes were registered. EVs were characterized and used in functional assays of hemostasis.

Results: Thirty patients with FN, 15 patients with FN+sepsis, as well as a control group of 30 patients with chemotherapy-induced uncomplicated neutropenia (i.e. without fever) were enrolled, with extremely low neutrophil and platelet counts (table 1). Sepsis onset in patients with FN was associated with significantly higher EV counts (figure 1a-f), with EVs from monocytes, granulocytes, neutrophils, and platelets carrying more tissue factor than those from patients with uncomplicated neutropenia (all P< 0.05). Despite these findings, EV-induced thrombin generation presented lower levels in patients with FN and sepsis, compared to uncomplicated neutropenia (figure 1g-h), along with a trend towards higher plasmin generation (figure 1i-j). Of note, cell-free DNA markedly increased after 72h of sepsis onset.

Conclusion(s): Our data demonstrated that while EVs seem to be involved in FN sepsis, a key element of immunothrombotic response is down-regulated during sepsis in the context of severe neutropenia and thrombocytopenia. Since the local generation of thrombin and hypofibrinolysis contribute to pathogen eradication, one could speculate that these findings could contribute to the increased severity of sepsis observed after FN.