Ovine red cell concentrates for transfusion research – is the storage lesion comparable to human red cell concentrates?

Abstract

Background and objectives Sheep are increasingly being used as a large in vivo animal model of blood transfusion because they provide several advantages over small animals. Understanding the effects of storage duration on ovine (ov) red cell concentrates (RCCs) and how these changes compare with stored human (hu) RCCs is necessary to facilitate clinical translation of research findings.Materials and methods OvRCCs (n = 5) collected and processed in standard human blood collection packs, and equivalent huRCCs provided by Australian Red Cross Lifeblood (n = 5), were stored at 2-6°C for 42 days, with samples collected weekly. Haemolysis index was determined by measuring supernatant haemoglobin concentration. Biochemical parameters were evaluated using a blood gas analyser. Energy metabolites and biologically active lipids were measured using commercial assays. Osmotic fragility was determined by lysis in various saline concentrations. Extracellular vesicles were characterized by nanoparticle tracking analysis. ResultsOvine red blood cells (RBCs) are double in number, smaller in size and more fragile than human RBCs. Haematological values were unchanged throughout storage. In contrast, biochemical and metabolic values, and haemolysis index in three of the five ovRCCs exceeded huRCCs licensing criteria by day 42. Accumulation of extracellular vesicles and biologically active lipids was comparable between huRCCs and ovRCCs. ConclusionThis study documents similarities and differences in the storage lesion of ovRCCs and huRCCs. This new information will guide the design of ovine transfusion models to enhance translation of findings to human transfusion settings.

Large Animal Models for Simulating Physiology of Transfusion of Red Cell Concentrates—A Scoping Review of The Literature

“…Slower metabolic rates in mature porcine erythrocytes compared to other mammalian red blood cells were also observed in a study by Dixon et al [74]. As pointed out in a recent publication by Simonova and colleagues, major differences in erythrocyte metabolism were also detected between ovine and human-packed red blood cells [63]. Especially maximum activity of glucose-6-phosphate dehydrogenase (G-6-PD), which serves an important role in protection against oxidative damage and glycolysis, was noticeably lower than in human erythrocytes [63,75,76].…”

“…Ovine and canine transfusion models included in this scoping review reported no data in this regard but generally described lower 2,3-diphosphoglycerate levels in ovine red blood cell units compared to humans in a previously published study by Baron et al [62]. Corresponding reductions of 2,3-diphosphoglycerate, glucose and adenosine triphosphate levels in ovine-packed red blood cells throughout storage were also reported in a recent study by Simonova et al [63]. The depletion of adenosine triphosphate levels in porcine-packed red blood cells occurred more rapidly than those reported in human units [22,25,26].…”

“…As pointed out in a recent publication by Simonova and colleagues, major differences in erythrocyte metabolism were also detected between ovine and human-packed red blood cells [63]. Especially maximum activity of glucose-6-phosphate dehydrogenase (G-6-PD), which serves an important role in protection against oxidative damage and glycolysis, was noticeably lower than in human erythrocytes [63,75,76]. Lower glycolytic activity and slower response to pH changes were furthermore reported in canine erythrocytes when compared with human red blood cells [77].…”

“…Lower glycolytic activity and slower response to pH changes were furthermore reported in canine erythrocytes when compared with human red blood cells [77]. As reported in other publications, ovine erythrocytes are more prone to osmotic fragility due to their spherical shape and smaller size compared to human red blood cells [63,78,79]. Therefore, for the translation of improved deformability of stored ovine erythrocytes by an ex vivo nitric oxide treatment prior to transfusion, as demonstrated by Muenster et al, further tests in humans are necessary [31].…”