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Science & Evidence

Over 35 peer-reviewed scientific papers demonstrating the characteristics of oxygen-controlled red blood cells processed by the Hemanext ONE® System have been cited over 2,000 times, as confirmed by Google Scholar.

The Association for the Advancement of Blood & Biotherapies (AABB) awarded Hemanext Inc. the AABB Research Innovation in Scientific Excellence (RISE) award in 2021 for an “original research article of impeccable study design, innovation, significance and effective communication”. The award embraces any area of knowledge covered by the journal Transfusion.

Featured Publications

The Benefits of Oxygen-controlled Storage with 

Preserves RBC Quality and Function Throughout Storage

Oxygen-controlled storage protects red blood cell (RBC) health and integrity, delivering higher-performing RBC that may function closer to freshly donated RBC at transfusion.1

Improves Oxygen Delivery to Human Tissue

In a human kidney model, oxygen-controlled RBC (hypoxic RBC) delivered oxygen to tissue more effectively than conventional RBC.11

Increases Microvascular Perfusion

Improved deformability and reduced endothelial adhesion support better microvascular flow in vitro and may lower vaso-occlusive risk in sickle cell disease.12,13

Reduces Risk of Iron-Related Stress

By preserving more viable RBC and reducing transfusion burden, oxygen-controlled RBC may help limit oxidative stress and iron overload in transfusion-dependent patients.

Has the Potential to Reduce Transfusion Burden

In an animal model of hemorrhagic shock, 21-day-old oxygen-controlled RBC restored blood pressure, oxygen delivery, and preserved organ function with about half the transfusion volume required compared to conventional blood.5

Hemanext ONE: Building Clinical Evidence

The first in-human studies show that oxygen-controlled RBCs are safe and well-tolerated, meeting all clinical and laboratory safety endpoints.19,20 Multiple ongoing/planned trials are evaluating oxygen-controlled RBC in hematologic malignancies, thalassemia, sickle cell disease, and trauma.

Oxygen-controlled Storage Preserves RBC Quality and Function

Oxygen-controlled storage limits oxygen-driven damage and helps red cells behave more like freshly donated blood at transfusion. By reducing oxidative stress and preserving ATP and 2,3-DPG, oxygen-controlled cells stay flexible, functional and structurally more viable than conventionally stored units throughout their shelf-lives.2–6

Oxygen-controlled storage minimizes the oxidative damage that accumulates during conventional storage, helping preserve red cell metabolism and structural integrity. Removing oxygen before storage reduces oxidative injury and reactive oxygen species (ROS) formation.7,8 Oxygen-controlled conditions maintain higher ATP and 2,3-DPG levels, supporting improved energy metabolism and faster oxygen-unloading based on an in vivo model.2,4 As a result, RBC remain more deformable and biochemically viable even at 42 days of storage.3,6

Publications
Oxygen-controlled Storage Improves Oxygen Delivery

What if more of every transfused unit actually stayed in circulation and delivered oxygen like freshly donated RBC?2,4,8 Oxygen-controlled storage preserves red blood cell function, improves 24-hour in vivo recovery, and maintains oxygen-offloading ability compared to conventionally stored blood.2,6

Oxygen-controlled storage preserves red blood cell (RBC) integrity in ways that may translate meaningfully into clinical benefit. RBC stored under low-oxygen conditions retain key metabolic pathways and structural stability, allowing more transfused RBC to remain in circulation and continue delivering oxygen for longer periods. As a result, patients may experience more durable hemoglobin responses and potentially longer intervals between transfusions.4,9

These advantages are supported by in-vivo data; healthy-volunteer studies confirmed improved survival and persistence of oxygen-controlled RBC in the subjects’ circulation.4 The oxygen-controlled RBC demonstrated higher 24-hour post-transfusion recovery after 42 days of storage compared with conventionally stored units, meeting and exceeding established quality thresholds.6,10

Beyond cell survival, oxygen-controlled RBC also preserve physiological oxygen-offloading. Recent work shows that oxygen-controlled RBC improve oxygen-release kinetics comparable to freshly donated blood.2,11 Data obtained from resuscitation of animals in hemorrhagic shock also supports more efficient oxygen delivery at the tissue level.5

Together, these data show that Hemanext ONE delivers red blood cells that survive longer in circulation, and maintain faster oxygen-unloading, offering a meaningful improvement over conventional storage.2,6

Publications
Oxygen-controlled Storage Increases Microvascular Perfusion

Oxygen-controlled red cells stay more flexible and interact less with the endothelial cells—key advantages for patients with sickle cell disease.14

Oxygen-controlled storage reduces oxygen exposure, helping limit the oxidative and structural deterioration that drives the storage lesion. Donor RBC stored under oxygen-controlled conditions show reduced adhesion to thrombospondin-1 (TSP-1) and human umbilical vein endothelial cells and maintain higher deformability and rheologic properties under flow, supporting faster microvascular perfusion.12,13

These benefits extend to plasma from patients with sickle cell–specific conditions. In a patient-specific compatibility study, oxygen-controlled RBC retained significantly higher deformability, experienced less oxidative injury, and hemolyzed less when exposed to the inflammatory and oxidative plasma of patients with sickle cell disease, including samples collected during vaso-occlusive crises.3

By maintaining RBC flexibility in hostile plasma environments and reducing adhesive interactions with the endothelium, oxygen-controlled storage may enhance microvascular perfusion and support better post-transfusion survival in sickle cell disease, with potential to reduce transfusion frequency and related complications.3,12,13

Publications
Oxygen-controlled Storage Reduces Risk of Iron-Related Stress

Oxygen-controlled storage helps red blood cells (RBC) break down less, potentially lowering the release of free hemoglobin and reactive iron after transfusion. This may reduce oxidative stress and slow the progression of iron overload in chronically transfused patients.4,5,7,13,15–17

Oxygen-controlled storage slows the oxidative damage that drives hemolysis, keeping red cells intact and potentially limiting the rise of free hemoglobin during storage. With fewer cells breaking down, patients are exposed to far less non-transferrin bound iron (NTBI), a key contributor to oxidative injury after transfusion. By preserving membrane stability and reducing hemolysis, oxygen-controlled RBC may meaningfully slow the pace of iron loading in chronically transfused patients.4,13,16–18

In addition, oxygen-controlled RBC demonstrated improved 24-hour recovery and faster oxygen unloading, so fewer units may be required to achieve the same hemoglobin targets thus potentially decreasing transfusion burden.2,6 Preclinical models have shown equivalent hemoglobin restoration with fewer units of oxygen-controlled RBC5, a finding consistent with improved post-transfusion recovery in healthy-volunteer studies.4

Publications
Oxygen-controlled Storage Has the Potential to Reduce Transfusion Burden

In an animal model of severe hemorrhagic shock, 21-day-old oxygen-controlled RBC improved outcomes compared with conventionally stored units.

Oxygen-controlled RBC restored mean arterial pressure, cardiac function, and systemic vascular resistance with ~50% less transfusion volume required. They also produced a more favorable physiologic response, limiting metabolic acidosis, reducing lactate accumulation, and decreasing tissue hypoxia and organ injury across the liver, kidney, and lung.5

Inflammatory markers were markedly lower, including reduced IL-6 and CXCL1, and oxygen-controlled RBC preserved left-ventricular cardiac function, whereas conventionally stored RBC impaired these indices.5 These findings align with improved post-transfusion recovery observed in human volunteer studies, supporting the concept that oxygen-controlled RBC deliver oxygen more efficiently and function more like fresh blood.2,4,17

Collectively, these data suggest that oxygen-controlled storage has the potential to reduce transfusion volume while improving physiologic recovery.

Publications
Hemanext ONE: Building Clinical Evidence

Hemanext ONE is advancing through a growing clinical development program across several transfusion-relevant patient groups. A first-in-human safety study in Norway demonstrated that oxygen-controlled red cells were safe and met all clinical and laboratory objectives.19,20

A randomized, controlled trial is now underway evaluating the efficacy of oxygen-controlled RBC in patients with hematologic malignancies, focusing on transfusion effectiveness, hemoglobin response and safety assessments.

In the United States, Hemanext has received NIH funding to initiate a trial of oxygen-controlled RBC in patients with sickle cell anemia, where improved deformability, lower adhesion, and reduced hemolysis are highly relevant (NIH Award Number R44HL178006.)

Together, these clinical efforts reflect a broad and growing evidence base designed to evaluate oxygen-controlled RBC across the conditions in which red cell performance matters most.

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Sustaining the red blood cells that sustain life.
  1. Muller C, Courelli V, Govender K, et al. Hypoxically stored RBC resuscitation in a rat model of traumatic brain injury and severe hemorrhagic shock. Life Sciences. 2024. Doi: https://doi.org/10.1016/j.lfs.2024.122423.
  2. Rabcuka J, Blonski S, Meli A, et al. Metabolic reprograming under hypoxic storage preserves faster oxygen unloading from stored red blood cells. Blood Adv. 2022; 6(18):5415-5428. Doi: 10.1182/bloodadvances.2022007774.
  3. Karafin MS, Field J, Ilich A, et al. Hypoxic storage of donor red cells preserves deformability after exposure to plasma from adults with sickle cell disease. Transfusion. 2022;1-10. Doi: 10.1111/trf.17163.
  4. D’Alessandro A, Yoshida T, Nestheide S, et al. Hypoxic storage of red blood cells improves metabolism and post-transfusion recovery. Transfusion. 2020;60(4):786-798.
  5. Williams AT, Jani VP, Nemkov T, et al. Transfusion of anaerobically or conventionally stored blood after hemorrhagic shock. Shock. 2020;53(3):352-362.
  6. ClinicalTrials.gov. Clinical investigation to evaluate the Hemanext® oxygen reduction system-pivotal trial. Accessed December 15, 2025. https://clinicaltrials.gov/ct2/show/results/NCT03301779?view=results.
  7. Yoshida T, Shevkoplyas SS. Anaerobic storage of red blood cells. Blood Transfus. 2010;8(4):220-36.
  8. Yoshida T, Blair A, D’Alessandro A, et al. Enhancing uniformity and overall quality of red cell concentrate with anaerobic storage. Blood Transfus. 2017;15(2):172-181.
  9. Carter P and Dunham A. Modeling hemoglobin levels of patients chronically transfused with red blood cells. Transfusion. 2023;1-8. Doi: 10.1111/trf.17305.
  10. Dumont LJ, Yoshida T, AuBuchon JP. Anaerobic storage of red blood cells in a novel additive solution improves in vivo recovery. Transfusion. 2009;49(3):458-64.
  11. Rabcuka J, Fallon J, Meli A, et al. Storage under hypoxia improves the ability of red cells to release oxygen in ex vivo perfused human kidneys. Blood Red Cells & Iron. 2025. Doi: /10.1016/j.brci.2025.100038.
  12. Burns JM, Yoshida T, Dumont LJ, et al. Deterioration of red blood cell mechanical properties is reduced in anaerobic storage. Blood Transfus. 2016;14(1):80-88.
  13. Bencheikh L, Nguyen K-A, Chadebech P, et al. Preclinical evaluation of the preservation of red blood cell concentrates by hypoxic storage technology for transfusion in sickle cell disease [Letter to the Editor]. Haematologica. 2022;107.
  14. Inusa Baba, Atoyebi W, Andermariam B, Hourani J, and Omert L. Global burden of transfusion in sickle cell disease. Transfusion and Apheresis Science. 2023. Doi: https://doi.org/10.1016/j.transci.2023.103764.
  15. Yoshida T, Prudent M, D’Alessandro A. Red blood cell storage lesion: causes and potential clinical consequences. Blood Transfus. 2019;17(1):27-52.
  16. Rapido F, Brittenham G, Bandyopadyay S, et l. Prolonged red cell storage before transfusion increases extravascular hemolysis. J Clin Invest. 2017;127(1):375-382. Doi:10.1172/JCI90837
  17. Carter P and Dunham A. Modelling haemoglobin incremental loss on chronic red blood cell transfusions. Vox Sanguinis. 2022;1-8. Doi: 10.1111/vox.13261.
  18. Angoro B, Motshakeri M, Hemmaway C, et al. Non-transferrin bound iron. Clinica Chimica Acta. 2022:157-167. Doi: 10.1016/j.cca.2022.04.004.
  19. Reikvam H, Hetland G, Ezligini F, et al. Safety of hypoxic red blood cell administration in patients with transfusion-dependent hematological malignancies: an interim analysis. Transfusion and Apheresis Science. 2023. Doi: https://doi.org/10.1016/j.transci.2023.103755.
  20. Reikvam H, Kristofferson E, Felli Lunde T, et al. Transfusion of hypoxic red blood cells to hematologic malignancy patients and acutely bleeding burn patients. Poster presented at: The Association for the Advancement of Blood & Biotherapies; October 19-22, 2024; Houston, TX.

By producing higher quality RBCs, the Hemanext ONE system has the potential to enable fewer and more effective transfusions for patients. I am truly excited by the possibility of bringing this improved red blood cell replacement therapy to populations in the U.S. that have been waiting for a transformative technology like this one.

Dr. Philip C. Spinella
Professor, Department of Surgery and Department of Critical Care Medicine at University of Pittsburgh

We value our partnership with Hemanext to enhance blood product quality and availability. Hemanext ONE has the potential to strengthen the resiliency of the blood supply, and this FDA authorization is a significant milestone to that end.

Ralph Vassallo, MD, FACP
Executive Vice President, Chief Medical and Scientific Officer of Vitalant

The Hemanext ONE system offers promise to improve the treatment landscape for patients burdened by transfusions and could be an essential step towards performing fewer and better transfusions. Having long championed Hemanext’s transformative initiatives, I eagerly anticipate witnessing the positive influence, right here in the United States, on the advancement of transfusion therapy quality.

Paul M. Ness, MD
Former Director, Division of Transfusion Medicine at Johns Hopkins University and board member of Hemanext

By deoxygenating red cells and maintaining them in their hypoxic state throughout storage, the resulting red cells experience less oxidative stress and oxidative damage, have improved metabolism, and are also more deformable leading to improved micro vascular profusion and less hemolysis.

Dr. Steven Spitalnik, MD
Co-Director of the Laboratory of Transfusion Biology, Colombia University

The preclinical data by Williams et al. show anaerobically stored RBCs achieve multiple clinically important functional resuscitation goals, with a smaller volume of fluid and the FDA benchmark of 24-hour RBC recovery. I look forward to the clinical trials in bleeding patients.

John Holcomb, MD, FACS
University of Alabama at Birmingham

I have had several patients who have received Hemanext hypoxic blood, and several of the patients have personally said thanks for having been given the opportunity and also that they have felt better after transfusion with hypoxic blood compared to conventional transfusion. One must of course be careful not to attach too much importance to such observations, but I would still like to mention that there has been a remarkable tendency towards this.

Håkon Reikvam, MD, PhD
Professor, Department of Clinical Science, University of Bergen, Norway
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