grouP O wholE blooD (LTO-WB): storagE leSion impacT And infLammation – PEDESTAL

Haemorrhage is one of the leading causes of preventable death in the military in combat. Currently, most patients receive blood components (red blood cells, platelets, plasma) rather than whole blood. Whole blood has the advantage of simplifying resuscitation logistics, providing physiological ratios of components, reducing storage volumes and allowing transfusion of younger platelets and red cells. However, this product has not been used in civilian medicine in France yet, although it is already in the United States.
This leads doctors deployed on external operations (OPEX) to use plasma, red blood cells and platelets. However, platelet concentrates may not be available on mission, as their storage conditions and shelf life are not always compatible with OPEX logistics. Thus, only the use of group O leukocyte-depleted whole blood without haemolysin (or Low Titer O Whole Blood, LTOWB), which gathers the three elements into physiological proportions, enables to address this problem. However, although studies have shown the efficacy of this product to stop bleeding, their inflammatory potential linked to the presence of platelets, has not been investigated yet. In addition to their haemostatic role, platelets are also involved in inflammation, particularly by releasing numerous immunomodulatory molecules.
The main objective of our research project is to use in vitro and in vivo tools to characterise innovative labile blood products (LBP), including LTOWB, transfused in civilian and military medicine, focusing on the inflammatory characteristics of these LBP.
The development of in vitro and in vivo tools to define biomarkers is essential to optimise the use of these LBP, relatively to the therapeutic indication. Relating these biomarkers to the efficacy of transfusions will help in the decision-making process regarding the benefit/risk ratio of transfusions that may occur in rural and austere environments, such as OPEX.
Therefore, we aim to characterise different platelet products, including LTOWB, using two approaches, in vitro and in vivo:
(i) In the in vitro approach, we will quantify the soluble inflammatory factors and microvesicles released by LTOWB platelets, and assess platelet activation, apoptosis, autophagy and respiratory metabolism. We will also analyse the ability of platelets to promote inflammation through their interactions with endothelial cells and neutrophils. These different platelet parameters will be analysed relatively to the preparation process and storage time of each platelet product.
ii) In the in vivo approach, we will evaluate the transfusion performance of human platelet products characterised in vitro and transfused into an immunodeficient mouse model (NSG) with induced thrombocytopenia or massive haemorrhage. Possible thrombotic complications will also be evaluated.
This study will have a major impact on the health care practices related to LBP in the very specific context of military medicine, particularly in OPEX.
This project reflects our will to structure an INSERM-EFS-CTSA consortium, capable of gathering skills and technologies adapted to the development and evaluation of LBP intented for civilian and/or military medicine applications. It will also enable us to position the EFS and the CTSA, in reinforced collaboration, at the international level, in a very competitive field regarding the dynamism of the research activities of the military transfusion services (including American services).