PB0773 - Platelet number and function alterations in preclinical models of sterile inflammation and sepsis patients: implications in the pathophysiology and treatment of inflammation

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Co-Author(s)

MV

María Villa-Fajardo

Research technician
Department of Hematology, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clínico San Carlos
Madrid, Madrid, Spain
MY

María Cecilia Yáñez Palma

Emergency physician
Department of Emergency, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clínico San Carlos (HCSC)
Madrid, Madrid, Spain
Andrea Acebes-Huerta, PhD

Postdoctoral researcher
Instituto de Investigación Sanitaria del principado de Asturias (ISPA)
Oviedo, Asturias, Spain

Presenting Author(s)

Patricia Martínez-Botía, MSc

PhD student
Instituto de Investigación Sanitaria del Principado de Asturias (ISPA)
Oviedo, Asturias, Spain

Co-Author(s)

MM

Marjolein Meinders

Researcher
Dept. of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam
Amsterdam, Noord-Holland, Netherlands
MN

Martijn A. Nolte

Group leader
Dept. of Hematology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam
Amsterdam, Noord-Holland, Netherlands
CB

Celina Ma Benavente Cuesta

Dr.
Department of Hematology, Hospital Clínico San Carlos, Madrid, Spain
Madrid, Madrid, Spain
JE

Johannes A. Eble

Professor
Institute of Physiological Chemistry and Pathobiochemistry, University of Münster
Munich, Bayern, Germany
Jd

Juan González del Castillo

Emergency physician
Department of Emergency, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clínico San Carlos (HCSC)
Madrid, Madrid, Spain
FM

Francisco Javier Martín-Sánchez

Emergency physician
Department of Emergency, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clínico San Carlos (HCSC)
Madrid, Madrid, Spain
LG

Laura Gutiérrez

Principal Investigator - Platelet Research Lab
University of Oviedo - ISPA
Oviedo, Asturias, Spain

Background: Platelet transfusions are given to thrombocytopenic sepsis patients at risk of bleeding, which pose an increased risk of transfusion related adverse events including acute lung injury (TRALI). Emerging evidence points to platelets and neutrophils as major contributors to TRALI, as targeting platelet function ameliorates its risk in preclinical models. However, current anti-platelet agents would also compromise their hemostatic function and therefore, are not suitable as treatment in this context.

Aims: To characterize platelet function in the context of inflammation (sepsis).

Methods: We have characterized the platelet aggregation capacity in a receptor-wise manner in murine preclinical models of acute (LPS-induced) and chronic (CD70Tg) sterile inflammation, and in a cohort of sepsis patients. The study was approved by the respective Ethical Committees. Flow cytometry-based platelet aggregation assays (FCA) were done.

Results: Platelets from day 5 LPS-treated mice (i.e., when a new batch of platelets has been produced under inflammatory conditions) displayed an aggretin A (CLEC2)- and collagen (α2β1/GPVI)-induced aggregation defect, similarly to platelets from CD70Tg mice, which also displayed a PMA (αIIbβ3)-associated impairment (Figure 1). A reduced response was observed in human sepsis platelets, stratified by count, with aggretin A, convulxin (GPVI) and ristocetin (vWF receptor) (Figure 2A). The plasma from sepsis patients displayed a tendency to alter platelet quiescence and to inhibit healthy-donor platelet aggregation (Figure 1B).

Conclusion(s): While the platelet aggregation signature of inflammation differed inter-species, our results suggest a specific “shutdown” of the non-hemostatic or immune receptors (CLEC2, GPVI), which occurs at the platelet production level and is tuned or primed further in the circulation. These results led us to hypothesize that “inflammation-conditioned” platelets are produced with a specific receptor function profile to avoid an exacerbated inflammation response that could represent danger to the body’s well-being. Our results have implications in the treatment and in the indication of platelet transfusions in sepsis patients.