Blood transfusions are a common part of modern medicine and have been used to save human patients for 200 years. Biobanks play an integral part in this process by collecting and storing units of blood from blood donors. According to the World Health Organization, 112.5 million blood donations are collected each year (1). Around 85 million units of blood are given to patients each year (2). However, there is still a blood shortage in many parts of the world. One of the reasons for this is that red blood cells (RBCs) can only be stored at 4°C for up to 42 days.
The FDA and other regulatory agencies limit blood storage in biobanks to 42 days because RBCs deteriorate over this time. They undergo significant biochemical, physiological and structural changes, which are called the RBC Storage Lesion. This deterioration rate is different in blood from different donors, but it isn’t clear exactly which factors contribute to these inter-donor differences (3). Some of the changes in metabolite levels are reversible once the blood is transfused into patients but some of the structural changes are permanent.
Large Blood Biobanking Study
REDS-III (Recipient Epidemiology and Donor Evaluation Study-III) is a large seven-year, international, multi-center study launched by the US National Heart, Lung and Blood Institute, a division of the National Institutes of Health (NIH). The project will study blood biobanking and transfusion methods with the goal of improving the safety and availability of blood products in the US. They aim to collect data from 14,000 blood donors.
Metabolomics Studies in Blood Biobanks
Large-scale studies like REDS-III are now possible thanks to the rise of ‘omics platforms. Scientists now have the ability to characterize global changes in gene, protein and metabolite expression within cells and tissues stored in biobanks. Genomic, proteomic and metabolomic studies look at cell function. This data is particularly valuable if scientists repeat experiments at different time points to analyze functional changes in stored samples over time.
Scientists can use computational modelling to integrate different types of datasets into new models of how these biological changes occur in biobanked samples. These models can then be tested to see whether they are true.
Metabolism Deteriorates in Biobanked RBCs
Metabolomics studies have found that metabolic changes occur within days in biobanked RBCs. Multiple independent studies have shown that RBCs undergo two major metabolic shifts at roughly day 10 and day 17 of storage. This means that throughout the 42-day storage life cycle in biobanks, RBCs have three different metabolic phases.
During the first phase, the sugars fructose and mannose in the donor plasma are metabolized and depleted. However, adding more fructose and mannose to storage media does not help prevent metabolic deterioration and movement through the three metabolic phases (2). Most of the adenine in storage media is also metabolized during the first phase. However adding extra adenine does not change the metabolism of the stored RBCs. Furthermore, while the type of storage media seems to affect RBC metabolism of individual metabolites, it does not affect the overall transitions into the three different metabolic phases (2). This result was consistent across four of the most commonly used media in Europe and the US.
Storage temperature does affect RBC degradation, as would be expected. One study looked at the effects of storing RBCs at 4°C, 13°C or 22°C for 21 days or at 37°C for 7 days. RBCs went through the same three different metabolic phases at all temperatures, but the deterioration happened faster at higher temperatures. Researchers saw similar changes in RBCs stored at 13°C for 14 days and RBCs stored 4°C for 42 days.
Biomarkers of RBC Health
It is expensive and time-consuming to generate and analyze full metabolic datasets. Not all blood biobanks have the resources and expertise to monitor the health of their stored RBCs in this way. A more practical method is to use a small panel of biomarkers than can indicate the health and functionality of stored cells.
One study by Paglia et al. suggests that eight extracellular metabolites – glucose, lactate, malate, adenine, hypoxanthine, nicotinamide, 5-oxoproline and xanthine – can be used to distinguish between the three different metabolic phases in RBCs stored in biobanks (4). These results were verified in an independent lab with a different sample set.
Blood products stored in biobanks are valuable resources that saves millions of lives around the world each year. If we could extend the shelf life of blood products stored in biobanks, these products could potentially save even more people and would be easier to transport to disaster areas or to countries that have blood shortages.
- Blood safety and availability. World Health Organization. (Online) Accessed 23 October, 2018
- Yurkovich et al. Systems biology as an emerging paradigm in transfusion medicine. BMC Syst. Biol. 2018
- Jani et al. Blood Quality Diagnostic Device Detects Storage Differences Between Donors. IEEE Trans Biomed Circuits Syst. 2017
- Paglia et al. Biomarkers defining the metabolic age of red blood cells during cold storage. Blood. 2016