Background: Omics technologies represent a new analytical approach that allows a full cellular readout through the simultaneous analysis of thousands of molecules. The application of such technologies represents a flourishing field of research in human medicine, especially in transfusion medicine, while their application in veterinary medicine still needs to be developed. Summary: Omics technologies, especially proteomics, metabolomics, and lipidomics, are currently applied in several fields of human medicine. In transfusion medicine, the creation and integration of multiomics datasets have uncovered intricate molecular pathways occurring within blood bags during storage. In particular, the research has been directed toward the study of storage lesions (SLs), i.e., those biochemical and structural changes that red blood cells (RBCs) undergo during hypothermic storage, their causes, and the development of new strategies to prevent them. However, due to their challenges to perform and high costs, these technologies are hardly accessible to veterinary research, where their application dates back only to the last few years and thus a great deal of progress still needs to be made. As regards veterinary medicine, there are only a few studies that have focused mainly on fields such as oncology, nutrition, cardiology, and nephrology. Other studies have suggested omics datasets that provide important insights for future comparative investigations between human and nonhuman species. Regarding the study of storage lesions and, more generally, the veterinary transfusion field, there is a marked lack of available omics data and results with relevance for clinical practice. Key Messages: The use of omics technologies in human medicine is well established and has led to promising results in blood transfusion and related practices knowledge. Transfusion practice is a burgeoning field in veterinary medicine, but, to date, there are no species-specific procedures and techniques for the collection and storage of blood units and those validated in the human species are univocally pursued. Multiomics analysis of the species-specific RBCs’ biological characteristics could provide promising results both from a comparative perspective, by increasing our understanding of species suitable to be used as animal models, and in a strictly veterinary view, by contributing to the development of animal-targeted procedures.

The term “OMICS” embodies a new analytical approach that allows the simultaneous analysis of multiple molecules to investigate, and then attempt to understand, a biological system as a whole. The milestones of omics technologies have been metabolomics and genomics, developed at the end of the 20th century, and from which all other omics fields such as proteomics and lipidomics rapidly followed thanks to overwhelming technological progress. As knowledge increased, it became clear that this new approach was useful not only in the study of the physiological processes but also in the pathological ones, from etiopathogenetic, screening, diagnostic as well as therapeutic perspectives. In fact, integrating datasets from different biological domains by using a multiomics approach leads to a deeper knowledge of biological pathways and how environmental factors, diseases, or other variables might perturb them [1, 4].

Among many applications of omics technologies in medical fields, recent focus on omics applications to transfusion medicine has generated valuable novel insights, which will be summarized in this review. In fact, an ever-growing number of scientists perceive omics analysis as the future of the study of ex vivo preserved blood cells and their storage lesions (SLs), and thus for the development of new storage strategies [5]. The aim of this review was to summarize the multiomics approach applicability’s areas in human medicine, with particular regard to transfusion medicine and, consequently, to focus attention on the advances made by veterinary medicine on this topic, trying to provide interesting insights into this field to date little investigated in veterinary transfusion medicine.

In the last decades, a new concept of molecular, knowledge-based medicine has gained ground in the scientific community [1, 2]. The foundations of this revolutionary progress date back to the advent of the “big four omics” (i.e., genomics, transcriptomics, proteomics, and metabolomics) [6]. These, as well as other omics disciplines that originate from them (i.e., epigenomics [7], exposomics [8], transcriptomics [9], lipidomics [10], microbiomics [11], etc.), study biological systems at one specific molecular level, from the hereditary information stored within the genome to the RNA transcripts that are generated from it [12] and then the proteins [13] or metabolites that constitute the end-products of cellular activities, in both physiological and pathological cellular phases [2, 4]. While research was initially focused only on the identification and study of genetic and phenotypic variants, as knowledge improved and thanks to the development of high-throughput technologies [14, 16], it became clear that, actually, only pieces of a much more intricate puzzle were being studied. Thus, the so-called “multi-omics” approach aims precisely to study molecular pathways by integrating and comparing large amounts of data simultaneously, in order to uncover the intricate mechanisms underlying multifactorial diseases, as well as novel strategies for the prevention, accurate diagnosis, and effective therapy [17] in a global-unbiased and systematic manner at a high accuracy [1, 4, 12].

As already mentioned, the development of increasingly sophisticated and accurate biological systems has gone hand in hand with the development of equally cutting-edge and increasingly precise technology. In particular, mass spectrometry (MS) technology, nuclear magnetic resonance spectroscopy, and MS-based techniques are the most widely used in omics studies [1, 2]. In recent decades, omics technologies have been increasingly applied to human transfusion medicine, particularly focusing on the study of red blood cell (RBC) SLs [18, 19] and on new strategies to prevent them [5, 20, 21], which will be discussed in more detail in the next paragraphs.

Omics disciplines are furthermore used in the study of many other human diseases, such as cancer [12, 22], Alzheimer’s disease [23], cardiometabolic diseases [24], inflammatory bowel disease [25], immune-mediated disorders [26], and so many others [10, 17, 27, 28]. As regards veterinary medicine, this approach has been scarcely investigated to date [29, 31].

Because of their structural and functional perceived “simplicity,” RBCs were not long ago considered to be mere oxygen carriers and inert bystanders of the metabolic processes [32]. Since the beginning of this century, however, these old theories were completely subverted through the introduction of the multiomics approach and the concept of systems biology in transfusion medicine; in fact, metabolomics and proteomics have uncovered molecular pathways and an ultrastructural complexity previously unexpected for these cells with seemingly simple function [19, 33].

In 2011, the National Heart, Lung and Blood Institute (NHLBI), by launching the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) [34], paved the way for the concept of the RBC-Omics study. Omics studies were therefore undertaken as a key to defining SLs causes (genetic, epigenetic, and molecular) and their progression during RBCs conservation, as well as their potential consequences and novel strategies to prevent them [19].

Storage Lesions from an “Omics Point of View”

The term “SLs,” widely established and explored in the human literature [18, 35], refers to all those RBCs’ structural, morphological, and functional alterations occurring when, removed from the blood flow, they are processed and then placed under hypothermic storage conditions (1–6°C) up to a maximum of 7 weeks. Omics fields most explored in the study of RBCs are proteomics, metabolomics, and lipidomics. These are used to investigate, both qualitative and quantitative, the molecular changes that cells undergo during storage speculating on their causes and then allowing the design of strategies to prevent those expressions of cell damage [19].

In fact, SLs arise as a result of several mechanisms involving different molecular layers. These mechanisms include impaired metabolism of RBCs [5], the accumulation of oxidative stress, especially to the protein and lipid fractions [36], and an increased vesiculation rate [37], together leading to irreversible molecular and morphological alterations that result in increased osmotic fragility of the cells and thus improved susceptibility to hemolysis [19]. Omics studies have highlighted that during hypothermic storage, biochemical reactions proceed at decreased rates [38] but still occur in the absence of those protective mechanisms that are present “in vivo” [39]. First of all, a progressive depletion of essential substrates such as glucose and urate [40] and an important decrease in high-energy compounds such as adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) occur [5, 19]. Depleted ATP consequently impairs the functionality of critical ATP-dependent ion pumps in maintaining the sodium/potassium/calcium and osmotic homeostasis of RBCs and impairs protein phosphorylation as protein kinases require ATP to work [19, 41]. Oxidative stress and accumulation of reactive oxygen species (ROS) then play a key role in the development of SLs as they result in a cascade of events that leads to impaired metabolic and redox homeostasis, especially from the second week of storage [16]. In fact, even if RBCs are strongly equipped to fend of oxidative stress, since they are constantly exposed to oxygen due to their carrier activity, during storage an imbalance occurs between the production and accumulation of ROS and the ability of antioxidant defenses, such as methemoglobin reductase, to combat these reactive products [42]. A key role in RBCs’ ability to cope with oxidative stress is also played by the Band 3 heteroprotein complex and the related molecules affecting its activity. Indeed, through this complex, glucose utilization is broken down by the cell through two main glycolytic pathways: glycolysis, which promotes increased ATP and 2,3-DPG concentrations, and the pentose phosphate pathway pathway, which generates reducing equivalents in the form of NADPH essential for preserving glutathione homeostasis and therefore for preventing oxidative stress. This mechanism undergoes an oxygen-dependent modulation involving glycolytic enzymes and deoxygenated hemoglobin that compete for binding to the N-terminal cytosolic domain of Band 3 [15, 43, 44]. This modulation, crucial for gas transport homeostasis in vivo, is progressively lost under normal storage conditions, as illustrated by Rogers et al. [43] in a recent metabolomics study. Finally, harmful and waste products (such as oxidized proteins [45]) thus generated during ex vivo storage due to the aforementioned mechanisms, as well as during aging process in vivo, are discarded by RBCs through the vesiculation process [46]. Microparticle, also known as microvesicles or extracellular vesicles (EVs), release generates a progressive loss of membrane resulting in reduced cell deformability due to irreversible morphological changes (rheological properties). RBCs, therefore, change from the physiological discocyte form to an echinocytic and then sphero-echinocytic one, exacerbating in-bag hemolysis and potentially impairing the transfusion result [47, 48].

Storage Strategies

The appreciation and study of these SLs have driven omics technologies toward the research of storage quality markers (e.g., 2,3-DPG and ATP levels, absolute concentrations of supernatant hemoglobin [21], hypoxanthine and xanthine [49]) and the design of new strategies to improve quality and safety of blood products and transfusion medicine practices [50]. For this purpose, several RBC processing and storage strategies have been investigated.

Some of the most studied new strategies include the use of different additive solutions other than the commonly used [19]. For example, stored units can be added, with rejuvenating solutions containing pyruvate, inosine, phosphate, and adenine [51] or alkaline additives [41], which, in metabolomics studies conducted by Gehrke et al. [52] and D’Alessandro et al. [53], respectively, were found to be effective in restoring the energy and redox metabolism of RBCs. Another possible strategy is to supplement blood units with solutions containing antioxidant molecules such as vitamin E, which has been shown to reduce ROS formation [54], or vitamin C and N-acetylcysteine, which support antioxidant mechanisms through the ascorbate oxidation and the synthesis of new glutathione, thus preventing oxidative injury and reducing hemolysis levels during storage [55]. Moreover, there are procedures that can be directly applied to blood units and prior to storage, such as leukofiltration. This technique, also known as leukodepletion, is used to remove white blood cells and platelets, sources of ROS, and damage-associated molecular patterns that in the recipient patient may trigger proinflammatory, prothrombotic, and cytotoxic actions and may promote complement system activation [56]. Although literature data on the improved storability and safety of leukodepleted blood products are sometimes controversial [57, 58], a recently published proteomic study [59] highlighted a wide variation in the proteomic phenotype between leukoreduced and nonleukoreduced units obtained from the same donors and stored under the same conditions. Notably, in nonleukoreduced units, the proteome complexity observed was greater and the abundance of EV was higher, suggesting that there is an array of leukocyte- and platelet-derived proteins whose removal may result, for the reasons mentioned above, in better posttransfusion prognoses. Moreover, metabolomic and proteomic studies have explored the anaerobic storage of RBCs. This technique has been proposed to promote energy metabolism by removing a critical pro-oxidant factor [60].

Donor and Recipient Variables

Great attention has also been paid to potential donor characteristics that may positively or negatively influence metabolic and rheological properties of RBCs during storage and thus the goodness of transfusion practice, such as genetic variables (e.g., glucose-6-phosphate dehydrogenase deficiency [39]), donor gender, ethnicity and age, frequency of donation, and others [20, 61, 62]. Although collection, processing, and storage technologies applied to blood units lead to an unavoidable hemolysis’ rate (“spontaneous hemolysis”), it is also true that donor-related variables increase the susceptibility of RBCs to osmotic and oxidative hemolysis [63] due to differences in erythrocyte membrane composition, functionality and resilience [61, 64], EV production [65], hemoglobin levels and its stability [65], and antioxidant capacities [42]. For example, there is evidence of a lower susceptibility of female RBCs to lipid peroxidation, microvesicle formation, and hemolysis, possibly due to an estradiol and progesterone “protective” modulation [62, 65].

Biochemical and omics studies to identify reliable biomarkers for determining the metabolic status of stored RBCs [66], quality markers (e.g., uric acid [67] and hypoxanthine [49] levels have been proposed), and donor eligibility are essential to potentially minimize the risk of adverse effects of transfusion practice on recipients [41]. In fact, although discordant opinions exist, SLs accumulating during blood unit storage can result in proinflammatory and procoagulant stimuli and lead to significant clinical consequences [19, 68], especially in high-risk recipients such as trauma, pediatric, sepsis, or cardiac surgery patients [50, 68, 69].

Historically, man has always used animal-based research for medical purposes, by selecting animal species (such as rodents, pigs, primates, and others) that both share genetic or phenotypic features with humans and are easy to manipulate in preclinical experimental designs [70, 71]. Alongside the study of animal models for human diseases, as omics knowledge increased in human medicine, the multiomics approach began to be applied in the veterinary field with the aim of improving both animal and human health as well as animal husbandry productivity. As regards the “method” applicable in the study of omics profiles, the high-throughput technologies used in human medicine are the same as that suitable in veterinary medicine, as well as the different types of substrates that can be used, including plasma, serum, urine, feces, and saliva [31, 72, 73].

Over the past decades, pet owners have increasingly shown attention to their animals’ health and welfare, sharing environment and lifestyle with them, and therefore demanding quality standards comparable to those of human counterparts. So, given the ethical concerns surrounding the use of animal models [74], the omics approach in veterinary medicine can pursue animal physiopathology studies as part of a comparative medicine that can also provide benefits for human disease insights. In addition, omics sciences have been explored in livestock breeding where the study of omics biomarkers is applied to the clinical diagnosis of animal diseases [75] and to the quality and safety control of animal products [76] to safeguard consumers and public health.

However, although several metabolomic, proteomic, and lipidomic studies have been conducted on various animal species in recent years, some critical issues concerning the omics approach in veterinary medicine still exist: in particular (1) the existence of a wide heterogeneity among different animal species and breeds from an anatomical, physiological, and pathological point of view [31, 77]; and consequently (2) the challenges of establishing suitable reference intervals (RIs) for the studied parameters. To attempt and counteract some of this critical issue, Ottka et al. [30] conducted a large-sample multiomics study proposing canine RIs for 123 measurands belonging to different molecular classes (i.e., lipoproteins, fatty acids, triglycerides, amino acids, glycolysis-related metabolites, cholesterol, albumin, and creatinine) on serum and plasma specimens. The results were then reported for different animal age categories (i.e., puppies, adults and senior dogs). Even if these results need to be validated through additional studies, they provide an important basis for the development of further intra- and interspecific comparative omics studies. This is because understanding physiology and the availability of reliable RIs [78] are critical tools for health assessment and for the study of both diseases and new therapeutic approaches. Especially in the omics field in fact, where the majority of the studies are of comparative nature, having access to large and reliable databases as developed in human medicine, is mandatory to achieve solid results and not merely speculative ones [3].

Based on explored omics’ applicability in human medicine, wide possibilities also exist for veterinary species. Actually, veterinary clinical studies have been conducted on different topics and species. Major attention has been paid to veterinary oncology, not least because of the comparative insights with humans it provides. In particular, neoplastic diseases investigated through omics technologies are hematopoietic neoplasms [79, 82], mammary tumors [83, 85], oral neoplasms [86], neuroendocrine tumors [87], and melanocytic tumors [73, 88]. Further disorders addressed by omics approaches include cardiopathies [89, 91], endocrinopathies such as hyperadrenocorticism [92] and diabetes mellitus [93, 94], hepatopathies [95, 97], chronic kidney disease [98, 99], and inflammatory/infectious diseases(i.e., sepsis [100], pyometra [101], and vector-borne diseases [102, 103]). Interestingly, using omics approaches, great attention has also been paid to the gut microbiota [104, 105] and dietary regimens [106, 107]. Furthermore, as in human medicine, an increasing interest is being directed toward the applicability of omics technologies for transfusion purposes, which will be discussed below.

Omics Technologies in Veterinary Transfusion Medicine

Transfusion medicine is a specialized branch of medicine now widely applied in veterinary clinical practice too, in which animals (especially dogs, cats, and horses) can receive life-saving blood transfusions that may be necessary, following major blood loss due to traumas, surgery, anemias, and coagulopathies of various origins [29, 108, 113]. Compared to humans, a few articles are present regarding SLs in blood units from veterinary species. The majority of these studies have been conducted on dogs [114, 116], cats [117], and horses [118, 119], to identify and describe RBCs lesions that occur under different storage conditions, considering the impact of collecting and processing techniques such as leukofiltration [120, 121]. These studies have been conducted with nonomics technologies and they allowed the identification of some RBC SLs and the biochemical mechanisms involved in their development, undercovering variations among different species including humans. For example, during storage, the increase in potassium levels is lower in canine [115, 120] and feline [122] blood units when compared to human ones. This seems to be due to the lower intracellular potassium concentration coupled with the reduced activity and membrane concentration of Na/K-ATPase pumps in canine and feline erythrocytes [120]. This probably safeguards pets from potential posttransfusion complications related to hyperkalemia. Moreover, as in human, in nonhuman species 2,3-DPG levels progressively decrease during storage, but this phenomenon occurs more significantly in cats [122], whereas in horses the drop is far less marked than in the other species [118]. Even ATP concentrations see interspecific differences in the decrease of concentrations during storage. The feline species records, despite individual variability, a greater decline particularly during the first 7 days of storage [122], whereas the equine species displays the highest ATP concentration [118]. Interestingly, Dorneles et al. [119] examined the biochemical and hematological changes in whole blood units from Brazilian horses during a 28-day storage, finding that glucose levels diminished by more than 50%, which they described as a significantly greater decrease than that reported in humans and dogs, suggesting that it may be related to a greater metabolic activity of equine erythrocytes.

However, we are only at the dawn of the use of omics technologies in RBCs analysis in veterinary medicine and the very few studies available are recent even if most of them have no transfusion purposes. Nevertheless, they provide fundamental data regarding RBCs, especially canine ones, and use them as bases for future research directed toward this specific field of study.

In a case report published in 2018, Black and colleagues [123] used, for the first time, proteomics technologies to investigate the proteome of the RBCs in a dog suffering from hemolytic anemia neither immuno-mediated nor caused by toxins or infectious agents. They identified 408 proteins and, comparing them with the proteomic profile of a healthy dog, they found out that 252 of these showed increased or decreased levels in the affected dog. Most notably, decreased levels of alpha- and beta-adducin and a decrease in Band 3 were detected, which is a pattern that, in association with maintained levels of gamma-adducin, has also been reported in human hereditary spherocytosis [124]. In 2020, Prasinou et al. [125] were the first to study the lipid composition of the lipid bilayer of canine RBCs membrane using a lipidomic approach. On the basis of similar studies previously conducted on human RBCs’ lipidomic profile [126], they proposed a panel of 10 fatty acids, identified by profiling 68 healthy dogs, which could serve as a benchmark in future clinical studies on targeted diseases and responses to therapies. The suitability of studying the membrane lipid composition of RBCs lies in the fact that these cells are both large in number and unable to synthesize lipids themselves, so the fatty acids that build up their membrane are the result of interchanges with circulating lipoproteins and other cells and tissues. Then, the composition of the lipid bilayer strongly affects the metabolic homeostasis of the cell, the permeability and rheological properties of the membrane, and the functionality of proteins included in it [125, 126]. In 2021, Crisi et al. [127] compared the previously described results on healthy subjects [125] with the lipidomic profile of RBCs from dogs with chronic enteropathies, finding significant differences. In particular, they reported decreased levels of linoleic and palmitic acid in contrast to increased levels of dihomo-γ-linolenic acid methyl ester and stearic acids, reflecting abnormal metabolic pathways as observed in human enteropathies such as Crohn’s disease [128] and coeliac disease [129]. In addition, they observed an increase of membrane homeostasis indexes (i.e., unsaturation and peroxidation indexes) of diseased animals, suggesting higher susceptibility to oxidative damage.

Unfortunately, despite the ever-growing academics’ interest in veterinary transfusion medicine, we are only at the early days of the use of omics technologies in the analysis of both fresh and stored in veterinary blood bank RBCs, but with promising results. Particularly, the multiomic approach allows the evaluation of changes in multiple metabolites, enzymes, and lipids involved in the same metabolic pathway simultaneously in order to study it more thoroughly and better investigate species particularities, species-specific differences, and changes that occur during blood storage. Probably the first of these studies dates back to 2015, when Purcell and colleagues [130] conducted a genomic and proteomic analysis of both leukoreduced and nonleukoreduced canine-packed RBCs to investigate the variation, during storage, in cytokine concentrations. Interestingly, they observed that tumor necrosis factor-α and interleukin-1β concentrations do not increase significantly in packed RBCs during storage, in contrast to what happens in humans. Since interleukin-1β is one of the cytokines principally involved in febrile nonhemolytic transfusion reactions in people, they suggest that this finding may explain why this adverse reaction is very rarely observed in dogs.

According to the authors, the most relevant studies including different animal species and nonhuman primates are three articles belonging to the “Zoomics” project [29, 71, 131], an ambitious initiative recently set up with the purpose of studying species-specific characteristics of fresh and stored RBCs in order to extract useful results in both veterinary and comparative medicine. To date, by using an ultra-high-pressure liquid chromatography-MS-based approach, this research group has studied the metabolomic profile of RBCs from different species during a 42-day storage period under blood bank conditions, namely: olive baboon and rhesus macaque [70, 71], guinea pigs [131], dog, cow, horse, and donkey [29]. These study results revealed multiple species-specific similarities and differences. In particular, findings showed that RBCs from nonhuman primates had higher concentrations of all purine oxidation products, apart from urate, and higher concentrations of arginine and asymmetrical dimethylarginine than those from humans [70, 71]. However, the purine oxidation products reached the highest concentrations in the bovine species. The cow also showed the most distinct erythrocyte metabolic profile, characterized by the lowest levels of ATP, glycolytic metabolites, and glutathione and the highest levels in prostaglandins during storage, those making stored RBCs from this species the most susceptible to oxidative damage [29]. In contrast, equine (horse and donkey) erythrocytes were endowed with the most efficient energy metabolism and were the less prone to cold storage damage; both indeed showed the highest basal levels of antioxidant systems such as pentose phosphate pathway metabolites and glutathione levels as well as the highest concentrations of ATP, 2,3-DPG, and glycolytic metabolites [29]. As far as the horses are concerned, these latter results confirm what has been previously observed by Niinistö et al. [118]. Regarding dogs, which are currently the animal species with the most clinical applicability in veterinary transfusion medicine, they are characterized by the highest basal levels of ATP and S-adenosylmethionine. During storage, the canine metabolomic profile shows steady levels of S-adenosylmethionine and the highest amounts of free linoleic acid together with a high accumulation of hypoxanthine at the end of 42 days [29]. Notably, in man, hypoxanthine has been identified as metabolic markers of RBCs storage quality, as they are ROS sources via xanthine oxidase/xanthine dehydrogenase and thus correlated with the occurrence of SLs [49].

Multiomics is a burgeoning field in human medicine and is yielding promising insights into transfusion research. Omics studies can produce a large amount of data that also require analytical and integrative bioinformatics supports that allow the results to be correlated to the dynamics of many biomolecular processes of both physiological and pathological orders. In transfusion medicine, this approach made it possible to elucidate previously unexpected molecular pathways of RBCs, to appreciate the occurrence of SLs while speculating on potential consequences in recipient patients, and to propose new strategies for blood unit storage. However, the more detailed the omic study on cellular biomolecular pathways and the perturbative actions that the various exogenous and endogenous actions can determine (e.g., diseases, therapies, industrial processes such as blood conservation, etc.), the better scientific progress will also be to understand the details of systems biology.

Given these premises for human medicine, and given that omics technologies are currently expensive and hardly accessible to researchers, it is consequently unavoidable that a great deal of progress is still needed, especially in veterinary medicine. In the veterinary literature, the omics approach has been investigated by a few studies focusing on fields such as oncology [87], nutrition [132], endocrinology [94], cardiology [90], and nephrology [98]. Then other pioneering studies [30, 125] have proposed omics datasets that, although in need of validation, pave the way for future comparative research among human and nonhuman species. Concerning veterinary transfusion medicine, rare biochemical studies have investigated SLs and the mechanisms involved in their development, but there is a marked lack of omics investigations on the topic. The only published studies are the ZOOMICS © group’s metabolomic studies [29, 71, 131] and the multiomics ones by Stefanoni et al. [70] and Purcell et al. [130]. However, these studies represent only the basis for future research, which instead provides more detailed and specific biological results with relevant clinical implications.

Through this paper, we introduce our new research group working in the field of veterinary transfusion medicine, to the broad field of omics. By collaborating with the ZOOMICS © project research group and gaining access to highly sophisticated tools not usually accessible to veterinary clinicians, we aim to comparatively study the species-specific omics features of fresh and stored RBCs looking for features with clinical implications in veterinary transfusion medicine. In particular, we will focus on the identification of possible markers usable to select ideal donors, the development of species-specific additive solutions and processing techniques for blood units, the comparative study of SLs in different species and of new strategies to prevent them, and, not least, the study of potential posttransfusion adverse events in veterinary recipients.

The authors have no conflicts of interest to declare.

There is no funding to declare.

A.M. and V.C. have drafted the article and approved the final version. L.L, E.M., P.C., O.B., C.D., and M.T.A. have reviewed critically and agreed to the published version of the manuscript.

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Additional information

Arianna Miglio and Valentina Cremonini contributed equally to this work.