Exploring the hidden biochemical changes in stored red blood cells through the lens of Oscar Wilde's classic tale
In Oscar Wilde's 1890 novel The Picture of Dorian Gray, a handsome young man remains miraculously untouched by time while his portrait hidden in the attic ages grotesquely, recording every sin and year of passing time. 1
This timeless tale of hidden decay has found an unexpected parallel in modern medicine—not in art galleries, but in blood banks where stored red blood cells undergo their own hidden transformation while maintaining their outward appearance.
The "storage lesion" is the term scientists use to describe the collective damage that accumulates in blood during refrigeration, representing one of transfusion medicine's most intriguing puzzles. 3
How can something that looks perfectly viable outwardly be so altered internally? And what are the consequences when we transfuse this "Dorian Gray blood" into vulnerable patients? This article explores the fascinating science behind blood storage lesions and how researchers are working to reverse the hidden damage that accumulates in our life-saving blood supplies.
Healthy biconcave shape, optimal flexibility
Spiky, spherical shape with reduced functionality
When red blood cells are stored for transfusion, they don't simply wait patiently to be used. Instead, they undergo a series of profound biochemical and structural changes that begin almost immediately after collection. These alterations transform the cells in ways that may reduce their effectiveness after transfusion. 3
The standard storage period for packed red blood cells is 42 days in most countries (slightly longer in some regions), during which time the cells are maintained in specialized solutions at 1-6°C. While this cold temperature slows down metabolism, it doesn't stop it entirely, and the cells continue to consume energy and produce waste products in their confined environment.
One of the most significant changes occurs in the cells' energy systems. Red blood cells rely on adenosine triphosphate (ATP) for energy to maintain their shape and flexibility, but during storage, ATP levels decline steadily. This depletion has cascading effects on cellular function, impairing the ion pumps that maintain proper electrolyte balance and ultimately affecting the cell's physical properties.
Perhaps even more importantly, stores of 2,3-bisphosphoglycerate (2,3-DPG)—a crucial compound that helps hemoglobin release oxygen to tissues—become virtually undetectable after just two weeks of storage. Without 2,3-DPG, red blood cells become notoriously "stingy" with their oxygen, binding it more tightly and releasing it less readily to the tissues that need it most. This represents a particular problem for patients who receive transfusions specifically to improve their oxygen delivery.
The metabolic decline has visible consequences for the cells' physical form. Healthy red blood cells are famous for their biconcave disc shape—somewhat like a donut with a filled-in center—which provides optimal flexibility for navigating tiny capillaries. During storage, however, these sleek discs undergo a dramatic transformation, developing numerous spiky projections and becoming more spherical. These "spheroechinocytes" are far less deformable than their healthy counterparts, potentially impairing their ability to flow through the microcirculation.
Additionally, the storage process leads to vesiculation—the shedding of small fragments of cell membrane. These microvesicles accumulate in the storage bag and may contribute to inflammatory responses when transfused. The loss of membrane also reduces the cell's surface-to-volume ratio, further decreasing deformability and potentially marking the cell for early destruction by the recipient's immune system. 3
The most intriguing aspect of the storage lesion is its deceptive nature. Much like Wilde's protagonist, stored red blood cells often maintain their outwardly attractive appearance while hiding internal decay. To the naked eye—and even under basic microscopic examination—stored blood may appear perfectly normal, with the characteristic crimson color and absence of obvious clumping or debris. 1
This superficial preservation contrasts sharply with the significant functional impairments that have developed. The cells may still be able to carry oxygen (thanks to the hemoglobin that remains intact), but they've lost the sophisticated systems that make them effective delivery vehicles. This creates a situation where transfusion may correct anemia on paper (improving hemoglobin numbers) while providing less benefit than expected to the tissues themselves. 3
The parallel to Wilde's novel is striking: just as Dorian Gray's beautiful appearance masked his moral corruption, the seemingly intact red blood cells may hide significant functional deficits that only become apparent after transfusion. 1
One of the most promising areas of current research focuses on whether the storage lesion can be reversed—a process scientists call "rejuvenation." A fascinating study led by Kurach et al. (2014) explored this very question by testing a rejuvenation treatment on red blood cells at various time points during storage. 2
Packed red blood cells were prepared according to standard blood banking procedures and stored under typical blood bank conditions.
At each predetermined time point, samples were treated with the rejuvenation solution containing metabolites designed to boost energy production.
Treated cells were incubated at refrigeration temperatures for specified periods to allow metabolic recovery.
Researchers evaluated multiple parameters including ATP and 2,3-DPG levels, cell morphology, membrane flexibility, markers of oxidative damage, and vesiculation.
Treated cells were compared to untreated controls stored for equivalent periods. 2
These findings suggest that while some aspects of the storage lesion may be reversible—particularly metabolic deficits—other changes, especially structural alterations, may represent more permanent damage. The window of opportunity for meaningful intervention appears to be limited to the first few weeks of storage. 2
Understanding and addressing the storage lesion requires specialized reagents and approaches. Here are some key tools scientists use in this research: 2
| Reagent/Solution | Primary Function | Research Significance |
|---|---|---|
| Additive Solutions (AS-1, AS-3, AS-5) | Extend shelf life of stored red blood cells by providing nutrients and stabilizing the cellular environment. | Serves as the baseline storage medium for control comparisons in experimentation. |
| Rejuvenation Solutions | Typically contain pyruvate, inosine, phosphate, and adenine to boost energy metabolism in stored cells. | Allows researchers to test potential reversal of storage lesions and metabolic deficits. |
| Adenine | Precursor for ATP synthesis, helps maintain energy levels in stored cells. | Critical component of storage solutions; studied for optimal concentration to balance benefit and toxicity. |
| Mannitol | Osmotic stabilizer that helps prevent hemolysis (rupturing) of red blood cells during storage. | Used to investigate and mitigate membrane fragility during extended storage. |
| SAGM Solution | (Saline-Adenine-Glucose-Mannitol) A common additive solution used in Europe for red blood cell storage. | Provides standardized comparison for international research on storage solutions. |
| Nitric Oxide (NO) Donors | Compounds that release nitric oxide, helping to study vasodilatory effects and oxygen delivery capabilities. | Used to investigate microcirculatory effects of transfused blood and potential interventions. |
| Flow Cytometry Antibodies | Antibodies targeting specific membrane proteins (CD47, CD55, CD59) to assess membrane changes during storage. | Enables precise quantification of vesiculation and marker expression changes during storage. |
The metaphor of Dorian Gray's portrait continues to be remarkably apt for understanding the paradox of blood storage. Like the fictional painting, stored red blood cells accumulate hidden damage that belies their outward appearance—a trade-off that has allowed life-saving blood banking but may come with functional costs. 1
Ongoing research continues to reveal the complex changes that occur during storage and their potential consequences for transfusion recipients. While complete prevention of the storage lesion remains elusive, advances in rejuvenation techniques and storage technologies offer hope for improving the quality of stored blood and potentially enhancing patient outcomes. 2 3
As Wilde noted in his novel, "The true mystery of the world is the visible, not the invisible." The challenge for transfusion medicine is to look beyond what's visible in stored blood and address the hidden changes that may affect its life-giving properties. 1 4
Understanding storage lesions improves transfusion outcomes for vulnerable patients
New solutions and techniques continue to enhance blood storage methods
Artificial blood substitutes may one day eliminate storage concerns