WBC-Reduced Components

This section focuses on a crucial modification applied to cellular blood components: Leukocyte Reduction. This process involves removing the vast majority of white blood cells (WBCs or leukocytes) from Red Blood Cell (RBC) and Platelet units before transfusion. It has become a standard of practice in many parts of the world due to its significant benefits in reducing certain transfusion-related complications

What are Leukocyte-Reduced Components?

• Definition: Blood components (primarily RBCs and Platelets) that have undergone a process to significantly decrease the number of contaminating leukocytes (WBCs) present in the final product
• Goal: To minimize the adverse effects associated with transfusing donor WBCs along with the intended therapeutic cells (RBCs or platelets)

Why Leukoreduce? (Rationale & Benefits)

Transfusing donor leukocytes can lead to several undesirable outcomes. Leukoreduction aims to mitigate these risks:

• ****Reduce Febrile Non-Hemolytic Transfusion Reactions (FNHTRs):** This is one of the most common transfusion reactions. It’s often caused by:
  • Cytokines (like IL-1, IL-6, TNF-α) released by WBCs accumulating during storage
  • Recipient antibodies reacting against donor HLA antigens or other antigens present on the transfused WBCs
  • Benefit: Removing WBCs significantly reduces the cytokine load and the antigenic stimulus, thus lowering the incidence of FNHTRs
• ****Reduce/Prevent HLA Alloimmunization:** Exposure to foreign HLA antigens present on donor leukocytes can cause the recipient to develop HLA antibodies. This is particularly problematic for:
  • Patients requiring long-term platelet support (can lead to platelet refractoriness)
  • Patients awaiting organ or hematopoietic progenitor cell (HPC) transplantation (can complicate matching and increase rejection risk)
  • Benefit: Reducing the number of transfused WBCs decreases the recipient’s exposure to foreign HLA antigens, lowering the risk of developing HLA antibodies
• ****Reduce Risk of Transmitting Cell-Associated Viruses:** Certain viruses, most notably Cytomegalovirus (CMV), primarily reside within leukocytes
  • Benefit: Removing WBCs significantly reduces the amount of transmissible CMV. Leukoreduction is considered largely equivalent to providing CMV-seronegative blood (“CMV safe”) for preventing transfusion-transmitted CMV infection, especially for RBCs. (Note: For highest-risk patients like CMV-negative transplant recipients receiving cells from a CMV-positive donor, CMV-seronegative units might still be preferred by some clinicians if available.)
• ****Potential Other Benefits (Less definitively proven or primary indications)**
  • May reduce transfusion-associated immunomodulation (TRIM) - the subtle immunosuppressive effects sometimes attributed to transfusion
  • May reduce transmission of certain bacteria that can be carried by WBCs

How is Leukoreduction Achieved? (Methods)

• Filtration: This is the most common method
  • Pre-storage Leukoreduction (Preferred Method): Filtration occurs at the blood collection center shortly after collection, before the component is stored. This is typically done using specialized filters integrated into the blood collection set or attached via sterile connection devices
    • Advantages: Removes WBCs before significant cytokine accumulation occurs; allows for better quality control by the blood center
  • Post-storage / Laboratory Leukoreduction: Filtration occurs in the hospital transfusion service laboratory just before the unit is issued. Less common now for routine LR
  • Bedside Leukoreduction: Filtration occurs during transfusion using a specific leukoreduction filter at the patient’s bedside
    • Disadvantages: Less effective at preventing FNHTRs caused by pre-formed cytokines; quality control is more variable; requires specific bedside filters distinct from standard blood filters
• ****Apheresis Collection:** Many modern apheresis instruments are designed to collect platelet products (and sometimes RBCs) that are already significantly leukocyte-reduced as part of the automated collection process
• ****Buffy Coat Removal (Less Common in North America):** A processing method used in some regions where the WBC-rich buffy coat layer is physically removed during component preparation

Standards and Quality Control

To be labeled as “Leukocytes Reduced,” a component must meet defined standards for residual WBC content:

• AABB / US Standard: Residual WBC count must be < 5 x 10⁶ per final component (for RBCs and apheresis platelets)
• Council of Europe Standard: Often stricter, requiring < 1 x 10⁶ residual WBCs per final component
• Quality Control: Blood centers must perform regular QC testing on a sample of units to ensure their leukoreduction processes consistently meet these standards

Which Components are Leukoreduced?

• Red Blood Cells (RBCs)
• Platelets: (both Apheresis/SDP and pooled WBD units)

Note Plasma and Cryoprecipitate are essentially leukocyte-free due to the centrifugation processes used in their preparation, so leukoreduction is not applicable. Granulocytes are never leukoreduced, as leukocytes are the intended therapeutic component

Usage: Universal vs. Indicated Leukoreduction

• Universal Leukoreduction (ULR): This is the standard practice in many developed countries (including the US, Canada, UK, etc.). Nearly all cellular components (RBCs, Platelets) are leukoreduced for all patients. This approach simplifies inventory management and ensures the benefits are provided broadly without needing specific physician orders for LR
• Indicated Leukoreduction: In regions without ULR, leukoreduction might be specifically ordered for patients with known indications (e.g., history of FNHTRs, transplant candidates, chronically transfused patients)

Impact on Product

• Expiration Date: If performed using a closed system (e.g., pre-storage filtration, sterile connection), leukoreduction does not change the original expiration date of the component
• Cell Loss: There is a minimal loss of RBCs or platelets during the filtration process, but it’s generally not considered clinically significant
• Cost: Leukoreduction adds a small incremental cost to the blood component due to the filter and processing

Key Terms

• Leukocyte (WBC): White blood cell
• Leukoreduction (LR): The process of removing leukocytes from cellular blood components
• Febrile Non-Hemolytic Transfusion Reaction (FNHTR): A common reaction characterized by fever, chills, and sometimes rigors, not caused by red cell destruction
• HLA Alloimmunization: Development of antibodies against Human Leukocyte Antigens from a non-self source (like a transfusion)
• Platelet Refractoriness: Poor platelet count increment after transfusion, often due to HLA antibodies
• Cytokines: Signaling proteins released by cells (including WBCs) that mediate inflammation and immune responses
• CMV (Cytomegalovirus): A virus commonly transmitted via leukocytes
• Pre-storage Leukoreduction: Removal of WBCs at the blood center before storage (preferred method)
• Bedside Leukoreduction: Removal of WBCs during transfusion using a bedside filter (least preferred method)
• Universal Leukoreduction (ULR): Policy of providing leukoreduced components to essentially all patients