How Protein Science is Revolutionizing Transfusions
When blood leaves the human body and enters storage bags, its cells don't simply pause—they begin to change, often for the worse.
These accumulated changes, known as "storage lesions," include metabolic shifts, oxidative damage, and cellular breakdown that may reduce transfusion effectiveness and occasionally cause adverse reactions in patients 1 .
During storage, red blood cells gradually break down metabolic sugars, producing lactate and protons that decrease pH levels 8 . Meanwhile, cold storage reduces the pumping of sodium and potassium, leading to increasingly elevated potassium levels in the storage fluid 1 .
Enter proteomics, the comprehensive study of proteins. If you think of DNA as the blueprint for life, proteins are the workers that carry out those instructions.
The proteome—all the proteins produced in a biological system—is incredibly dynamic, changing based on the type and functional state of a cell 2 . By studying these protein patterns in stored blood, scientists can now detect early signs of deterioration long before they become visible under a microscope 3 .
Initial metabolic changes: pH decreases, lactate accumulates, 2,3-DPG levels begin to drop.
Protein modifications become detectable: oxidative damage, fragmentation, and aggregation.
Significant cellular changes: increased vesiculation, membrane damage, reduced deformability.
Proteomic technologies have evolved dramatically, allowing scientists to examine thousands of proteins simultaneously.
Proteins are separated based on their electrical charge and molecular weight, creating a pattern of spots on a gel 2 .
Acts as a molecular scale, identifying proteins based on their mass and charge with high sensitivity 2 .
Uses fluorescent dyes to compare multiple samples on the same gel, allowing researchers to see protein changes 2 .
Unlike DNA, which remains relatively stable, proteins constantly change in response to their environment—exactly what happens during blood storage. Red blood cells are particularly suited for proteomic analysis because they lack a nucleus and therefore cannot create new proteins; any changes to their protein profile during storage represent deterioration or modification of existing proteins 1 .
Scientists have discovered that a single red blood cell contains approximately 1,578 different cytosolic proteins and about 340 membrane-associated proteins 1 . This protein inventory provides a rich source of information about the cell's condition.
Could storing blood in oxygen-free environments prevent oxidative damage? Italian researchers decided to find out 1 .
If oxidative damage causes much of the storage-related harm to blood cells, could storing blood in oxygen-free environments prevent this damage? The research team hypothesized that storing blood in an atmosphere of inert gas (such as nitrogen) would slow or prevent these damaging oxidative processes 1 .
| Parameter Measured | Anaerobic Storage Effect | Significance |
|---|---|---|
| Protein Fragmentation | None detected in first 2 weeks; significantly reduced throughout storage | Complete prevention of early damage; 50-80% reduction overall |
| Hemolysis | Reduced | Fewer broken blood cells mean safer transfusions |
| 24-hour post-transfusion survival | Improved | More transfused cells continue circulating and functioning |
| ATP levels | Slower decrease | Better cellular energy maintenance |
| 2,3-DPG levels | Slower decrease | Better oxygen delivery capacity |
The progress in transfusion proteomics relies on sophisticated tools and reagents.
| Tool/Reagent | Function | Application in Transfusion Proteomics |
|---|---|---|
| Trypsin | Digestive enzyme that breaks proteins into smaller peptides | Prepares protein samples for mass spectrometry analysis by creating appropriately sized fragments 2 |
| Cyanine dyes (Cy2, Cy3, Cy5) | Fluorescent protein labels | Enable multiplexed analysis in DIGE, allowing comparison of multiple samples on the same gel 2 |
| Isobaric Tags (iTRAQ) | Chemical labels that incorporate stable isotopes | Allow precise quantification of proteins across different samples in mass spectrometry 6 |
| Combinatorial Hexapeptide Libraries | Protein-capturing beads | Concentrate low-abundance proteins while reducing dominant species, enabling detection of rare but important proteins 3 |
| Strong Cation Exchange Chromatography | Separates peptides based on electrical charge | Reduces sample complexity before further analysis, part of multidimensional separation strategies 2 |
| Reversed-Phase Chromatography | Separates molecules based on hydrophobicity | Final separation step before mass spectrometry, often coupled directly to the instrument 2 |
Proteomics doesn't work in isolation. The most exciting developments come from integrating multiple "omic" approaches.
Essential for controlling bleeding in cancer patients and during major surgeries, platelet concentrates have a remarkably short shelf life of just 4-7 days due to the "platelet storage lesion" 7 .
Integrating genomics, transcriptomics, proteomics, and metabolomics to build a comprehensive picture of blood biology .
Blood products might be matched to patients based on molecular compatibility, potentially improving outcomes for patients who require frequent transfusions .
A gene that, when dysfunctional, makes RBCs more likely to undergo programmed cell death .
Genetic variations that explain why different blood units break down at varying rates during storage .
Genetic factors affecting levels of this important compound, supplementation of which might improve stored blood quality .
The alliance between transfusion medicine and proteomics represents more than just technological advancement—it embodies a shift in how we approach blood safety.
Instead of reacting to problems, we're moving toward predicting and preventing them. By understanding blood products at the molecular level, we can ensure that the life-saving therapy of transfusion becomes even safer and more effective.
As research continues, the insights gained from proteomic studies promise to address some of transfusion medicine's most pressing challenges: making better use of limited blood donations, extending shelf life without compromising quality, and reducing rare but serious adverse reactions.
The journey toward perfect blood storage continues, one protein at a time.