Blood transfusion is one of the cornerstones of modern medicine, used in a spectrum of situations from traumatic injuries to chronic illnesses that impair red blood cell production. About every two seconds, someone in the U.S. needs blood. Yet, beneath the surface of this life-saving practice is a largely ignored issue that jeopardizes its efficacy: the quality of stored blood.
The science of blood transfusion seems simple but is deceptively complex. Although donors supply millions of units each year, the process of storing and using this blood is fraught with challenges. One critical concern is a phenomenon known as “blood storage lesion,” a combination of biochemical, mechanical, and functional changes that occur in red blood cells (RBCs) after they are collected and stored. Although these changes are invisible to the naked eye, their effects can be clinically significant.
The Invisible Problem with Stored Blood
To understand why blood storage lesion matters, we need to consider the unique biology of RBCs. Packed with a protein called hemoglobin, these specialized cells evolved to onload lung oxygen and then deliver oxygen efficiently to tissues. However, this finely tuned system works best when RBCs are actively circulating in the body; once donated and stored, their ability to function begins to degrade rapidly.
Within hours of storage, RBCs undergo significant biochemical changes. Levels of ATP (a chemical that maintains the biconcave disc shape of RBCs) and 2,3-DPG (a molecule that increases oxygen offloading of hemoglobin) plummet by up to 90% within the first few days. Mechanical changes also occur: Cell membranes lose flexibility and become “sticky,” impairing their ability to squeeze through tiny capillaries and circulate. Oxidative damage further compromises cell function, increasing the likelihood of rupture. The rate and severity of these changes vary depending on the donor, adding another layer of complexity to the phenomenon.
The Clinical Implications of Aging Blood
The risks posed by stored blood are not hypothetical. A 2022 Danish study suggested that “transfusing exclusively older RBC units stored for >1 or 2 weeks increases the 28-day recipient mortality and risk of thromboembolism or death compared with transfusing fresher RBC units.” This raises critical questions about the safety and effectiveness of current blood storage practices.
For years, researchers believed that the storage lesion developed gradually, and that blood stored for seven days was nearly as good as fresh blood. However, more recent studies indicate that the most critical damage occurs within the first few days of storage. This has profound implications for how we assess blood quality, because based on flawed assumptions about how damage accumulates, many clinical studies have underestimated the risks of using stored blood.
Part of the problem is that the tests to measure oxygen offloading, ATP levels, and DPG levels are time consuming and complicated, so they are rarely used. Thus, the efficacy of stored blood is assumed but not measured.
A Technological Revolution in Blood Transfusion
If stored blood loses its effectiveness so quickly, how can we improve the situation? Enter new diagnostic and therapeutic technologies designed to mitigate the effects of storage lesion.
The effectiveness of the transfusion of RBCs depends not only on blood flow but also on oxygen unbinding from hemoglobin and oxygen diffusion through the RBCs. Thus, the usual therapeutic strategies of packing the red cells with oxygen (breathing oxygen gas) and increasing blood flow (with drugs) do little to improve oxygen delivery to the body’s tissues, which is dominated by oxygen offloading.
A breakthrough innovation is FlowScore, a tool developed at the University of Oxford, UK. A “flow-cytometric proxy of the functional quality of blood,” it allows clinicians to assess the quality of stored blood quickly. The developers summarize its value thusly: “By evaluating how effectively red blood cells can unload oxygen to tissues, FlowScore provides a much-needed metric to determine whether stored blood is safe to use — or whether it requires rejuvenation.”
FlowScore can be measured with a device already available in most blood facilities. A hematological flow cytometer measures various physical and chemical properties of blood cells and is already widely used in clinical and research settings to analyze cells in a fluid suspension. These devices can be used to measure FlowScore with only a software upgrade. Given its ease of use, arguably, FlowScore should be measured for all blood units transfused.
For older blood with a low FlowScore, how can we “rejuvenate” blood? By restoring ATP and 2,3-DPG levels, as well as repairing oxidative damage, the FDA-approved rejuvesolR solution containing phosphate/inosine/ pyruvate/adenine (PhIPA) pharmacologically replenishes those key metabolic reserves. Combined with more efficient blood handling devices, PhIPA could significantly improve clinical outcomes for the millions of patients receiving transfusions.
The Road Ahead: Making Transfusions Safer
The implications of these advances are enormous. Recent studies show that rejuvenated RBCs have better survival rates and enhance heart, kidney, and lung function in transfusion recipients.
Together, FlowScore and PhIPA are likely to reduce morbidity and mortality by reducing complications like Transfusion-Related Acute Lung Injury (TRALI), one of the leading causes of transfusion-related deaths. In short, these integrated technologies — spanning diagnostic, therapeutic, and automated blood preparation — can establish new standards for blood storage and transfusion. These innovations promise not only to reduce morbidity and mortality but also to lower the overall demand for blood donations — a critical benefit in an era when blood supplies are often stretched thin.
While transfusions save countless lives every year, it’s time to rethink how we manage and use stored blood. The medical community, blood banks, and policymakers must work together to address the risks of aging blood by implementing these emerging technologies. Doing so will not only make transfusions safer but also ensure that this life-saving intervention is optimally effective.