The Blood Bag Revolution

Closing in on DEHP-Free Red Blood Cell Containers

How science is transforming a fundamental medical device to make blood transfusions safer

What is DEHP?

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer added to PVC to make it flexible. It's what gives traditional blood bags their soft, pliable quality but has raised health concerns due to its tendency to leach into stored blood products.

Key Facts
  • Used since the 1950s
  • Classified as "substance of very high concern" in EU
  • Potential endocrine disruptor
  • Leaches into blood products during storage
Research Progress
Safety Assessment 85%
Clinical Trials 70%
Regulatory Approval 60%
42

Days of blood storage

1950s

DEHP first used

2025

Landmark study published

3.23

ATP in DEHT (μmol/gHb)

Introduction: The Unseen Component in Blood Transfusions

When we think about blood transfusions, we envision advanced medical care, sterile equipment, and life-saving interventions. Few would imagine that a crucial component in this process isn't biological or electronic, but chemical—a plasticizer called DEHP that makes plastic blood bags flexible.

For decades, this unsung hero of blood storage has quietly performed its duty, preventing blood from deteriorating during refrigeration. But emerging research has revealed a troubling trade-off: while DEHP helps preserve blood, it also leaches into the blood supply, posing potential health risks. This discovery has launched a scientific race to develop safer alternatives without compromising blood quality—a race that is now approaching a breakthrough moment.

Benefits of DEHP
  • Reduces hemolysis
  • Maintains ATP levels
  • Preserves cell flexibility
  • Extends shelf life
Risks of DEHP
  • Endocrine disruptor
  • Developmental issues
  • Reproductive effects
  • Leaches into blood

The DEHP Dilemma: Solution and Problem in One Package

Why DEHP Took Center Stage

Since the 1950s, DEHP has been the undisputed champion of blood bag plasticizers worldwide. Its dominance wasn't accidental; DEHP provides critical preservation properties that initially seemed almost magical. Red blood cells stored in DEHP-plasticized bags maintain their integrity and functionality throughout the 42-day refrigerated shelf life.

How DEHP Works

DEHP molecules migrate from the plastic into the blood, where they integrate into cell membranes, stabilizing them against the stresses of refrigeration.

The Gathering Storm of Concern

By the turn of the millennium, troubling research began emerging about DEHP's potential as an endocrine disruptor—a substance that interferes with hormonal systems. Studies linked high exposure to developmental issues in children and reproductive effects in animals.

1950s

DEHP first introduced in blood bags for its superior preservation properties.

2000s

Research begins to reveal endocrine-disrupting properties of DEHP.

2010s

EU classifies DEHP as a "substance of very high concern", restricting medical use.

2020s

Intensive research into alternatives accelerates with promising results.

The Search for Safer Substitutes: A Scientific Breakthrough

Designing the Perfect Successor

The quest for a DEHP replacement presented a formidable challenge. Scientists needed a material that could match DEHP's preservation capabilities while being safer biologically.

Maintain Blood Quality
Meet Safety Standards
Work in Existing Systems
Be Cost-Effective

The Crucial Experiment: DEHT Takes Center Stage

In 2025, a landmark study published in Vox Sanguinis directly compared traditional DEHP-based blood bags with next-generation DEHT alternatives, marking a critical step toward DEHP-free blood banking 9 .

Study Methodology
Control Arm
  • Conventional 500-mL DEHP/SAGM bags
  • Standard preservation solution
Experimental Arm
  • Prototype 475-mL DEHT/PAGGSM bags
  • Enhanced preservation solution

Duration: 43 days (slightly beyond standard 42-day shelf life)

Key Metabolic Markers at Expiry (Day 43)
Parameter DEHP/SAGM DEHT/PAGGSM Statistical Significance
Supernatant K+ (mmol/L) 47.8 ± 4.7 48.8 ± 3.7 Not significant (p=0.346)
Hemolysis (%) 0.29 ± 0.10 0.33 ± 0.12 Not significant (p=0.083)
ATP (μmol/gHb) 2.83 ± 0.5 3.23 ± 0.58 Significant (p=0.004)
Free Fe2+ (μmol/L) 5.7 ± 1.1 8.4 ± 1.9 Significant (p<0.001)
Glucose (mmol/L) 18.1 ± 2.3 15.4 ± 1.7 Significant (p<0.001)
Key Finding

DEHT bags actually outperformed DEHP bags in maintaining adenosine triphosphate (ATP) levels—the energy currency of red blood cells. Higher ATP typically correlates with better post-transfusion survival and functionality.

Red Blood Cell Membrane Properties
Property DEHP/SAGM DEHT/PAGGSM Implication
Maximum Elongation Index 0.611 ± 0.010 0.581 ± 0.015 DEHT cells are less deformable
Force Required to Deform 1.834 ± 0.177 2.300 ± 0.288 DEHT cells require more force
Osmotic Fragility Normal range Shifted left DEHT cells more fragile in specific conditions

The membrane property data revealed that while DEHT successfully preserved red blood cells, it did so through different physiological mechanisms than DEHP—a crucial insight for future development.

The Scientist's Toolkit: Essential Research Components

Advancing DEHP-free blood storage requires specialized materials and methods. Here are the key components powering this research:

Research Tool Primary Function Application in Studies
Polymer Systems (PVC with alternative plasticizers) Provide inert, flexible containers that interact beneficially with blood components Primary blood storage containers; different polymers are tested for compatibility
Additive Solutions (SAGM, PAGGSM) Provide nutrients to extend shelf life of red blood cells Formulations are optimized for use with alternative plasticizers
Hemolysis Assays Quantify red blood cell rupture during storage Key quality metric for evaluating new container materials
Metabolic Profiling Measure ATP, glucose consumption, lactate production Assesses cellular health and energy status during storage
Membrane Characterization Tools (e.g., Lorrca) Analyze red blood cell flexibility and mechanical properties Critical for understanding how alternatives affect blood cell function
Analytical Techniques
  • Flow cytometry
  • High-performance liquid chromatography
  • Mass spectrometry
  • Electron microscopy
  • Rheometry
Quality Metrics
  • Hemolysis rate
  • ATP concentration
  • Potassium leakage
  • pH stability
  • Morphology index

The Road Ahead: Challenges and Future Directions

Beyond DEHT: The Expanding Universe of Alternatives

While DEHT shows significant promise, it's not the only candidate in development. The search for optimal blood storage materials has expanded along multiple parallel tracks:

Alternative Plasticizers

Besides DEHT, researchers are investigating other non-phthalate plasticizers with different chemical backbones.

Bio-based Polymers

Exploring fundamentally different materials that don't require plasticizers at all, including bioplastics.

Surface Modification

Coating the interior of blood bags with thin films that provide benefits without chemical migration.

The Sustainability Dimension

The push for DEHP-free blood containers coincides with growing interest in sustainable healthcare solutions. Researchers are now developing eco-friendly and biodegradable blood bags in response to environmental concerns about plastic waste from healthcare facilities 7 .

Sustainability Goals
Non-Toxic
Biodegradable
Manufacturing Efficiency
Global Standards

Implementation Hurdles

Transitioning to DEHP-free blood banking systems presents practical challenges that extend beyond the laboratory:

Regulatory Approval

Requires extensive safety and efficacy data across multiple jurisdictions with varying requirements.

Protocol Modification

Blood processing protocols may need modification for new materials, requiring staff retraining.

Cost Considerations

Must be balanced against safety benefits, especially in resource-limited settings.

Global Harmonization

Standardization remains a complex issue with different regions adopting different approaches.

Research Focus

Future work must "focus on impacts to the red blood cell membrane, with interrogation of hemolysis, microvesicle release, membrane composition, morphology, deformability and osmotic fragility" to fully realize DEHP-free blood storage 9 .

Conclusion: A Transfusion Turning Point

The journey toward DEHP-free blood containers represents a fascinating convergence of transfusion medicine, materials science, toxicology, and regulatory policy. What began as concern about a ubiquitous chemical has evolved into a sophisticated redesign of a fundamental medical device—one that touches millions of lives annually.

The progress has been remarkable. Where once DEHP seemed irreplaceable, researchers have now demonstrated that alternatives like DEHT can not only match but exceed some preservation properties of traditional systems. The 2025 study represents a watershed moment—proof that the biological trade-offs that once seemed inevitable may be surmountable through continued innovation.

As research continues to refine these alternatives and address remaining challenges, we're approaching a future where blood transfusions will be even safer—free from concerns about plasticizer exposure while maintaining the quality and efficacy that patients depend on. The blood bag revolution won't happen overnight, but science is steadily closing in on a solution.

Impact on Patient Care

Safer transfusions for vulnerable populations including neonates, pregnant patients, and those requiring multiple transfusions.

The Future of Transfusion Medicine

DEHP-free blood containers represent just one step in the ongoing evolution of safer, more effective blood products and transfusion practices.

References