The use of low titer group O whole blood (LTOWB) has increased in recent years, predominantly in the setting of adult trauma resuscitation. While randomized control trials have not yet shown LTOWB to be superior to standard component therapy, several clinical trials designed to test this hypothesis are ongoing. Most LTOWB units undergo prestorage leukoreduction by filtering out the leukocytes, or white blood cells, to an acceptable level, defined in the AABB Standards as less than 5 x 106 white blood cells per unit of whole blood.1 A recent commentary by Yazer et al. examined the benefits and limitations of leukoreduction (LR) of LTOWB, suggesting that LR of LTOWB could be optional for patients with life-threatening hemorrhage.2 Contrasting viewpoints are discussed by Adkins et al. 3
Benefits of Leukoreduction
In high-resource settings, such as the United States, LR is nearly universal. Established benefits of LR include a reduction in febrile nonhemolytic transfusion reactions (FNHTRs), decreased risk of transmission of pathogens found within leukocytes (e.g., CMV), and a decreased rate of alloimmunization to human leukocyte antigens (HLA).2 If a platelet-sparing filter is used, the unit retains many of its platelets.2,3 LR of LTOWB may reduce wastage, as a unit of LR LTOWB that has not been transfused and is approaching the end of its shelf life can undergo further manufacturing into a unit of LR red blood cells. LR red blood cells are more desirable than non-LR red blood cells, so leukoreduction of LTOWB facilitates this process.
Limitations of Leukoreduction
Despite the benefits conferred by LR of LTOWB, the practice is not without challenges. The LR process adds additional expense to the manufacturing process. 2 LR of a unit of LTOWB must be completed within 8 hours of collection, which restricts the distance from collection sites to manufacturing centers.2 The filter used to produce LR LTOWB units is platelet-sparing; however, some platelets are lost in the process of filtration. The clinical significance of this is unknown.2 Supply chain issues are also a concern for the manufacture of LR LTOWB. There is currently only one supplier of the kit used to manufacture LR LTOWB. The availability of LR LTOWB would be impacted by circumstances that affected the ability of the single supplier to manufacture these kits.2 LR also affects the shelf life of LTOWB, as LR LTOWB is collected in CPD with a platelet-sparing filter and has a shelf life of 21 days. Non-LR LTOWB collected in CPDA-1 has a shelf life of 35 days.2
Do Trauma Patients Require Leukoreduction of LTOWB?
Most LTOWB units are transfused to actively bleeding patients, such as trauma patients. Yazer et al. question whether actively bleeding patients are likely to benefit from leukoreduction. The authors argue that the benefits of increased availability of non-LR LTOWB may outweigh the benefits provided by LR. In the context of life-threatening bleeding, the prevention of FNHTRs, CMV transmission, and HLA alloimmunization by leukoreduction may become less critical concerns.2
Is a Move to Non-LR LTOWB Premature?
Adkins et al. suggest that adopting non-LR LTOWB may be premature, and stronger evidence is needed before implementing such a change.3 The authors also raise ethical considerations when moving away from leukoreduction, a practice which provides established benefits. They further suggest alternative solutions to address the limitations of LR LTOWB, such as improving the LR process, an area in which the Red Cross’s Transfusion Innovation Team is active,4 and diversifying suppliers to address supply chain vulnerabilities.3
For more information on LTOWB, please visit Low Titer O Whole Blood | American Red Cross.
References:
1. Association for the Advancement of Blood & Biotherapies. Standards for Blood Banks and Transfusion Services, 34th Edition effective April 1, 2024 (Published: 9/12/2024) [Internet]. Bethesda: Association for the Advancement of Blood & Biotherapies; 2024 Sep 12 [cited 2025 Jul 27]. Available from: http://standards.aabb.org/pages/external/standard.aspx?catalogId=275.
2. Yazer MH, Beckett A, Bloch EM, Cap AP, Cohn CS, Gurney J, Hermelin D, Spinella PC. It is time to reconsider leukoreduction of whole blood for use in patients with life-threatening hemorrhage. Transfusion. 2024 Dec;64(12):2391-2399. doi: 10.1111/trf.18047. Epub 2024 Oct 17. PMID: 39417564.
3. Adkins BD, Booth GS, Fasano RM, Gehrie EA, Gestring ML, Masel D, Nguyen PT, Refaai MA, Jacobs JW, Raza S, Vella MA, Tormey CA, Blumberg N. Eliminating leukocyte reduction for whole blood: Is it premature to consider this paradigm-changing practice? Transfusion. 2025 Feb;65(2):375-378. doi: 10.1111/trf.18113. Epub 2024 Dec 22. PMID: 39709612; PMCID: PMC11826295.
4. Wellington M, Feldman TP, Cleeton S, Sawyer S, Brown BL. Delayed Leukoreduction of whole blood with a platelet-sparing filter to increase low-titer group O whole blood production in the United States. Transfusion. 2023;63 Suppl 3:S177-S188. doi:10.1111/trf.17372
Caroline Miller, MD, is the medical director of the American Red Cross Tennessee Region.
