FAQ: Whole blood, leukocytes reduced (LrWB) at Canadian Blood Services

Author: Johnathan Mack, MD, MSc, FRCPC
Primary target audiences: Medical laboratory technologists, Transfusion medicine physicians
 

Background

Modern transfusion medicine began with whole blood transfusion. For decades, whole blood was the only available option for transfusion therapy. Once whole blood could be separated into individual blood components, component therapy (red blood cells [RBCs], platelets, and plasma) gradually replaced whole blood transfusion since it offered more targeted replacement.

There is increased interest in whole blood as a resuscitation therapy for hemorrhage. A growing body of evidence suggests that outcomes for trauma patients are improved with the early and balanced delivery of transfusion support. However, high quality evidence demonstrating the superiority of whole blood to component therapy is lacking.

Beginning in November 2022, Canadian Blood Services will manufacture whole blood, leukocytes reduced, for use by the Canadian Armed Forces when requested. This new blood component is available exclusively for military use, but future expansion to civilian use is under assessment.

Frequently Asked Questions

1.  What is whole blood, leukocytes reduced?

Whole blood, leukocytes reduced (LrWB) is a blood component that is manufactured using a platelet-sparing filter to reduce the number of leukocytes while preserving the platelet content. Each unit of LrWB is manufactured from an individual donation of whole blood.

Canadian Blood Services received Health Canada approval to manufacture and distribute LrWB in October 2022.

2.  How is LrWB manufactured?

As with conventional blood components (RBCs, platelets, frozen plasma), manufacturing of LrWB begins with a whole blood donation from a single donor. Approximately 500 mL of whole blood is collected from the donor into a collection system containing 70 mL of citrate-phosphate-dextrose (CPD) anticoagulant.

Following a room-temperature hold for a minimum of 4 hours, the bag of anticoagulated whole blood is connected to a whole blood filter system for gravity filtration and stored within 24 hours of stop bleed time. This system uses a platelet-sparing filter that removes leukocytes while maintaining the platelet concentration.

3.  How is LrWB stored and transported? When does it expire?

LrWB manufactured by Canadian Blood Services should be stored at 1–6˚C without agitation. LrWB collected in CPD expires after 21 days. Once punctured, units of LrWB should be transfused within 4 hours if stored at >6˚C, and within 24 hours if stored at 1–6˚C.

4.  How does LrWB compare with RBCs, pathogen-reduced pooled platelets, untreated pooled platelets, untreated apheresis platelets, and plasma components?

Table 1: Component characteristics of a typical unit of LrWB¹, RBC², pathogen-reduced pooled platelets³, pooled platelets⁴, untreated apheresis platelets⁵, and frozen plasma⁶ 

     * CPD: citrate phosphate dextrose; ACD-A: anticoagulant citrate dextrose, solution A
     ¹  known as Whole Blood, Leukocytes Reduced, in the Canadian Blood Services Circular of Information
     ² known as Red Blood Cells, Leukocytes Reduced (LR) in the Canadian Blood Services Circular of Information
     ³known as Pooled Platelets Psoralen Treated in the Canadian Blood Services Circular of Information
     ⁴ known as Pooled Platelets LR CPD in the Canadian Blood Services Circular of Information
     ⁵ known as Apheresis Platelets in the Canadian Blood Services Circular of Information
     ⁶ known as Frozen Plasma CPD in the Canadian Blood Services Circular of Information

5.  How are donations selected for LrWB?

LrWB units will be manufactured primarily using blood donations from group O donors with low-titre anti-A/B isohemagglutinins. Every Group O whole blood donation will have anti-A1 and anti-B isohemagglutinin titre testing. Donations from both RhD-positive and RhD-negative donors will be used. Only donations from male donors without ASA use in the 72 hours before blood collection will be used.

6.  Why is LrWB only manufactured using donations from male donors?

Male donors are selected to mitigate the risk of transfusion-related acute lung injury (TRALI) due to anti-human leukocyte antigen (HLA) antibodies that can develop as a result of pregnancy. For more on TRALI, see our publication, Transfusion-related acute lung injury.

7.  Why are donations from group O donors used?

LrWB contains donor RBCs and plasma, so both donor red cell ABO antigens and donor ABO antibodies are important considerations for recipient compatibility. In most situations, ABO-identical whole blood would be optimal for transfusion. However, in situations of active life-threatening bleeding, the ABO blood type of the patient is often unknown and waiting for blood typing results would result in unacceptable delays to life-saving transfusion support.

The use of group O LrWB provides RBCs that are compatible with all ABO blood types, with rare exceptions. While the plasma in group O LrWB contains both anti-A and anti-B antibodies (and is therefore incompatible with non-O recipients), the risk of a hemolytic transfusion reaction can be mitigated by using whole blood from donors with low titres of anti-A/B antibodies (low-titre whole blood) and limiting the volume of incompatible whole blood that is transfused.

Transfusion of blood components containing ABO-incompatible plasma has not been associated with increased risk of hemolysis, hemolytic reactions, or death compared with ABO-compatible components in bleeding.^1-3 In situations where the recipient ABO-type is unknown, the benefits of providing timely transfusion support must be weighed against the risks of transfusing potentially incompatible plasma.

8.  What anti-A/B titre is considered “low-titre”?

The definition of what qualifies as a “low” anti-A/B antibody titre varies globally.⁴ Canadian Blood Services uses an automated anti-A1 and anti-B isohemagglutinin titre test which is performed on each donation. The titre cut-off is 1:32, which is equivalent to a titre of approximately 1:128 at room temperature using the immediate spin (IS) manual method. Only donations with a titre <1:32 (<1:128 IS manual equivalent) will be used for LrWB manufacturing. This cut-off was chosen based on the experience of other blood manufacturers internationally and hemovigilance data that suggest acute hemolytic reactions are more likely to occur above this cut-off.

Information can be found in our FAQ on donor high titre isohemagglutinin (anti-A/anti-B) testing at Canadian Blood Services.

9.  Does using only low-titre anti-A/B, group O, LrWB eliminate the risk of severe hemolytic transfusion reactions when transfused to non-O patients?

The use of low-titre anti-A/B, group O, whole blood to manufacture units of LrWB reduces the risk of severe hemolytic transfusion reactions but does not eliminate the risk entirely. Although clinical evidence suggests transfusion of incompatible plasma does not increase the risk of severe hemolysis or transfusion reactions, the number of participants in published studies may be inadequate to detect weak associations with severe hemolytic reactions. If given to patients of unknown ABO type, LrWB should be reserved for treatment of clinically significant bleeding and recipients should be monitored for hemolysis following transfusion.

10.  How will LrWB be labelled?

An example of a LrWB label is shown below. The label is similar in appearance to other blood components. The low anti-A/B titre will be clearly indicated.

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11.  When should LrWB be used?

LrWB is indicated for the treatment of clinically significant bleeding. As of November 2022, Canadian Blood Services will be manufacturing and distributing LrWB on-demand exclusively to the Canadian Armed Forces.

12.  What are the benefits of LrWB?

LrWB offers logistic advantages compared with conventional blood components. Resuscitation is simplified, with replacement of RBCs, plasma, and platelets achieved in each LrWB transfusion, as opposed to three separate transfusions of conventional blood components.

Storage and preparation are also simplified with LrWB, since the component requires only refrigeration at 1–6˚C compared to three different storage conditions for conventional components. This allows LrWB to be stored in situations where storage conditions are limited (e.g., field hospitals). LrWB does not require agitation like platelets, nor thawing like frozen plasma (which decreases the time to transfusion). Additionally, a 21-day shelf life means LrWB can be stored for longer than either thawed plasma or platelets, making inventory management easier. This is particularly relevant for environments where maintenance of a platelet inventory is impossible.  

13.  What are the possible risks of LrWB?

Non-group O recipients of group O LrWB are at risk of acute hemolytic reactions due to anti-A/B antibodies in the plasma of LrWB. This risk is mitigated by the selective use of low-titre anti-A/B whole blood to manufacture LrWB units. Further risk reduction can be achieved by limiting the number of units of LrWB used in initial resuscitation, although the transfusion volume that may increase the risk of a hemolytic reaction has not been established.

Risks of adverse transfusion reactions are similar with LrWB compared with conventional components (see Chapter 10, Transfusion reactions). Cold-storage conditions decrease the risk of bacterial proliferation observed in untreated platelet components stored at room temperature.

14.  Who can request LrWB?

LrWB will initially be manufactured and distributed on-demand for use only by the Canadian Armed Forces. Expansion to include non-military use is being assessed. Hospital customers will not be able to order LrWB until the potential non-military requirement is better understood.

15.  Why is Canadian Blood Services manufacturing LrWB only for the Canadian Armed Forces?

The available high-quality evidence currently available does not suggest that whole blood is superior to conventional component therapy for clinical outcomes in clinically significant bleeding.^5-8

Military environments introduce challenges in the storage and preparation of blood components that render conventional component therapy impractical or, in some settings, impossible. LrWB addresses some of these logistical challenges, improving access to transfusion support for members of the Canadian Armed Forces.

16.  Will LrWB be available for non-military use in Canada?

Modelling indicates that Canadian Blood Services will be able to meet the LrWB need of the Canadian Armed Forces. Further work must be done to understand the potential demand for this component in non-military use. The experience with the manufacturing and distribution of LrWB for the Canadian Armed Forces will help to inform decision-making regarding the use of LrWB for non-military use and ensure that enough LrWB can be manufactured to meet potential transfusion needs.

The National Advisory Committee on Blood and Blood Products is conducting a survey of Canadian healthcare providers to gather perspectives on the non-military use of whole blood, leukocytes reduced (LrWB) in Canada. Canadian health-care providers can complete the online survey at Civilian Utilization of Whole Blood, Leukocytes Reduced.

References

1. Harrold, I.M., Seheult, J.N., Alarcon, L.H., et al. Hemolytic markers following the transfusion of uncrossmatched, cold-stored, low-titer, group O+ whole blood in civilian trauma patients. Transfusion 60 Suppl 3, S24-s30 (2020).
2. Seheult, J.N., Dunbar, N.M., Hess, J.R., et al. Transfusion of blood components containing ABO-incompatible plasma does not lead to higher mortality in civilian trauma patients. Transfusion (2020).
3. Yazer, M.H., Freeman, A., Harrold, I.M., et al. Injured recipients of low-titer group O whole blood have similar clinical outcomes compared to recipients of conventional component therapy: A single-center, retrospective study. Transfusion 61, 1710-1720 (2021).
4. Yazer, M.H. & Spinella, P.C. Review of low titre group O whole blood use for massively bleeding patients around the world in 2019. ISBT Science Series 14, 276-281 (2019).
5. Geneen, L.J., Brunskill, S.J., Doree, C., et al. The Difference in Potential Harms between Whole Blood and Component Blood Transfusion in major Bleeding: A Rapid Systematic Review and Meta-Analysis of RCTs. Transfusion medicine reviews 36, 7-15 (2022).
6. Crowe, E., DeSantis, S.M., Bonnette, A., et al. Whole blood transfusion versus component therapy in trauma resuscitation: a systematic review and meta-analysis. J Am Coll Emerg Physicians Open 1, 633-641 (2020).
7. Naumann, D.N., Boulton, A.J., Sandhu, A., et al. Fresh whole blood from walking blood banks for patients with traumatic hemorrhagic shock: A systematic review and meta-analysis. The journal of trauma and acute care surgery 89, 792-800 (2020).
8. Malkin, M., Nevo, A., Brundage, S.I., et al. Effectiveness and safety of whole blood compared to balanced blood components in resuscitation of hemorrhaging trauma patients - A systematic review. Injury 52, 182-188 (2021).