Authors: Johnathan Mack, MD, MSc, FRCPC
Original publication date: November 16, 2022
Last updated: June 12, 2025
Primary target audiences: Medical laboratory technologists, transfusion medicine physicians, nurses, hospital staff at sites involved in clinical studies using whole blood, leukocytes reduced.
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 (red blood cells, platelets, and plasma), component therapy 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.
Canadian Blood Services began manufacturing whole blood, leukocytes reduced in November 2022. The component was initially only available upon request for the Canadian Armed Forces. Following recommendations by the National Advisory Committee on Blood and Blood Products (NAC), expansion of LrWB availability to non-military use has been developed and beginning in January 2025, hospitals can request access to LrWB for use in clinical trials.1
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.
As with conventional blood components (e.g., red blood cells, platelets, frozen plasma), manufacturing of LrWB begins with a whole blood donation from a single donor. Approximately 480 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 is stored within 24 hours of the stop-bleed time. This system uses a platelet-sparing filter that removes leukocytes while maintaining the platelet concentration. See Figure 1.
For more information on LrWB, please read the Circular of Information.
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.
For more information on LrWB, please read the Circular of Information.
Table 1: Component characteristics of a typical unit of leukoreduced whole blood, red blood cells, pathogen-reduced, pooled platelets, pathogen-reduced apheresis platelets, and frozen plasma
| Component characteristic | Leukoreduced whole blooda | Red blood cellsb | Pathogen-reduced pooled plateletsc | Pathogen-reduced apheresis plateletsd | Frozen plasmae | S/D Plasma |
|---|---|---|---|---|---|---|
| Mean unit volume (mL) | 496 | 287 | 181 | 277 | 289 | 200 |
| Anticoagulant | CPD* | CPD* | CPD* | ACD-A* | CPD* | Sodium citrate |
| Approximate hematocrit (L/L) | 0.41 | 0.67 | - | - | - | - |
| Approximate hemoglobin (g) | 62 | 55 | - | - | - | - |
| Approximate platelet yield (x109 per unit) | 83 | - | 243 | 252 | - | - |
| Approximate factor VIII (U/mL) | 0.78 | - | - | - | 0.88 | 0 |
| Residual leukocytes (x106) | 0.2 | 0.06 | 0.04 | <5 | - | - |
| Component of shelf life (from day of blood collection unless otherwise specified) | 21 days | 42 days | 7 days | 7 days | 12 months when frozen, 120 hours once thawed | 12 months when frozen, 120 hours once thawed |
* CPD: citrate phosphate dextrose; ACD-A: anticoagulant citrate dextrose, solution A
a known as Whole Blood, Leukocytes Reduced, in the Canadian Blood Services Circular of Information
b known as Red Blood Cells, Leukocytes Reduced (LR) in the Canadian Blood Services Circular of Information
c known as Pooled Platelets Psoralen Treated in the Canadian Blood Services Circular of Information
d known as Apheresis Platelets Psoralen Treated in the Canadian Blood Services Circular of Information
e known as Frozen Plasma CPD in the Canadian Blood Services Circular of Information
LrWB units are 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 who have not used acetylsalicylic acid (ASA) in the 72 hours before blood collection will be used.
Male donors are selected to mitigate the risk of transfusion-related acute lung injury (TRALI), which can be caused by anti-human leukocyte antigen (HLA) antibodies that develop during pregnancy. For more on TRALI, see our publication, Transfusion-related acute lung injury.
LrWB contains donor red blood cells 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 red blood cells 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.2-4 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.
The definition of a “low” anti-A/B antibody titre varies globally.5 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.
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.
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. See Figure 2.
LrWB is indicated for the treatment of clinically significant bleeding. It is currently only available for hospitals participating in clinical trials and to the Canadian Armed Forces.
LrWB offers logistic advantages compared with conventional blood components. Resuscitation is simplified, with replacement of red blood cells, 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.
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.
The risks of adverse transfusion reactions with LrWB are similar to those associated with conventional components (see Chapter 10 of the Clinical Guide to Transfusion, Transfusion reactions). Cold-storage conditions decrease the risk of bacterial proliferation observed in untreated platelet components stored at room temperature.
Following NAC recommendations, LrWB will be manufactured and distributed on-demand for use by the Canadian Armed Forces and for non-military use by hospitals participating in clinical trials of LrWB. Hospital customers interested in accessing LrWB for use in a clinical trial should contact their Hospital Liaison Specialist to apply for access. Further expansion of LrWB availability for non-military use will be assessed as clinical evidence evolves.
The currently available high-quality evidence does not suggest that whole blood is superior to conventional component therapy for clinical outcomes in clinically significant bleeding.6-9
Clinical trials are being supported so that further data can be gathered to better understand the patient populations and clinical circumstances in which LrWB may be superior to conventional component therapy.
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.
Quick reference sheet
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Links
Mack, J. FAQ: Whole Blood, Leukocytes Reduced (LrWB) at Canadian Blood Services [Internet]. Ottawa: Canadian Blood Services; 2025 [cited YYYY MM DD]. Available from: https://profedu.blood.ca/en/transfusion/publications/faq-whole-blood-leukocytes-reduced-lrwb-canadian-blood-services