TY - JOUR
T1 - Platelet number and function alterations in preclinical models of sterile inflammation and sepsis patients
T2 - implications in the pathophysiology and treatment of inflammation
AU - Villa-Fajardo, María
AU - Palma, María Cecilia Y. ñez
AU - Acebes-Huerta, Andrea
AU - Martínez-Botía, Patricia
AU - Meinders, Marjolein
AU - Nolte, Martijn A.
AU - Cuesta, Celina Benavente
AU - Eble, Johannes A.
AU - del Castillo, Juan González
AU - Martín-Sánchez, Francisco Javier
AU - Gutiérrez, Laura
N1 - Funding Information: This study was partially supported by an RYC fellowship ( RYC-2013-12587 , Ministerio de Economía y Competitividad, Spain) and I+D Excelencia 2017 and 2020 project grants ( SAF2017-85489-P and PID2020-117265GB-I00 , Ministerio de Ciencia e Innovación -Spain- and Fondos Feder) to L.G and a Severo Ochoa Grant ( PA-20-PF-BP19-014 , Consejería de Ciencia, Innovación y Universidades del Principado de Asturias) to PMB. We thank Paloma Cerezo, Almudena Payero, María de la Poveda Colomo, Nuria Urquijo, María del Carmen Ovejero, Ángela Hernández, María Isabel Granados and Ana María Fernández for technical support. We are especially thankful to Dr. Jerard Seghatchian, who over the years has collaborated with us, feeding us with crucial questions in the field and, hence, inspiring research projects. Publisher Copyright: © 2022 Elsevier Ltd
PY - 2022/4
Y1 - 2022/4
N2 - Platelets are the blood cells in charge of maintaining the body hemostasis, recognising the damaged vessel wall, and providing the appropriate cellular surface for the coagulation cascade to act locally. Additionally, platelets are active immunomodulators. At the crossroads of hemostasis and inflammation, platelets may exert either beneficial actions or participate in pathological manifestations, and have been associated with the prothrombotic nature of multi-organ failure in systemic inflammation. Platelet number alterations have been reported in septis, and platelet transfusions are given to thrombocytopenic patients. However, the risk to develop transfusion related acute lung injury (TRALI) is higher in sepsis patients. In this manuscript we show that platelets produced during inflammation in preclinical mouse models of sterile inflammation display lower aggregation capacity when stimulating certain receptors, while responses through other receptors remain intact, and we name them “inflammation-conditioned” platelets. In a cohort of sepsis patients, we observed, as previously reported, alterations in the number of platelets and platelet hyperreactivity. Furthermore, we identified a receptor-wise platelet aggregation response disbalance in these patients, although not similar to platelets from preclinical models of sterile inflammation. Interestingly, we generated evidence supporting the notion that platelet aggregation capacity disbalance was partially triggered by plasma components from sepsis patients. Our findings have implications in the indication of platelet transfusions in sepsis patients: Are fully functional platelets suitable for transfusion in sepsis patients? Current Clinical Trials (RESCUE) will answer whether platelet production stimulation with thrombopoietin receptor agonists (TPO-RAs) could be a substitute of platelet transfusions.
AB - Platelets are the blood cells in charge of maintaining the body hemostasis, recognising the damaged vessel wall, and providing the appropriate cellular surface for the coagulation cascade to act locally. Additionally, platelets are active immunomodulators. At the crossroads of hemostasis and inflammation, platelets may exert either beneficial actions or participate in pathological manifestations, and have been associated with the prothrombotic nature of multi-organ failure in systemic inflammation. Platelet number alterations have been reported in septis, and platelet transfusions are given to thrombocytopenic patients. However, the risk to develop transfusion related acute lung injury (TRALI) is higher in sepsis patients. In this manuscript we show that platelets produced during inflammation in preclinical mouse models of sterile inflammation display lower aggregation capacity when stimulating certain receptors, while responses through other receptors remain intact, and we name them “inflammation-conditioned” platelets. In a cohort of sepsis patients, we observed, as previously reported, alterations in the number of platelets and platelet hyperreactivity. Furthermore, we identified a receptor-wise platelet aggregation response disbalance in these patients, although not similar to platelets from preclinical models of sterile inflammation. Interestingly, we generated evidence supporting the notion that platelet aggregation capacity disbalance was partially triggered by plasma components from sepsis patients. Our findings have implications in the indication of platelet transfusions in sepsis patients: Are fully functional platelets suitable for transfusion in sepsis patients? Current Clinical Trials (RESCUE) will answer whether platelet production stimulation with thrombopoietin receptor agonists (TPO-RAs) could be a substitute of platelet transfusions.
KW - Flow cytometry
KW - Platelet aggregation
KW - Platelet transfusion
KW - Sepsis patient
KW - TRALI
UR - http://www.scopus.com/inward/record.url?scp=85126313255&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.transci.2022.103413
DO - https://doi.org/10.1016/j.transci.2022.103413
M3 - Article
C2 - 35288057
SN - 1473-0502
VL - 61
JO - Transfusion and apheresis science : official journal of the World Apheresis Association
JF - Transfusion and apheresis science : official journal of the World Apheresis Association
IS - 2
M1 - 103413
ER -