FAQ: Leucodepletion of red cells and platelets

Leucodepletion is a technical term for the removal of leucocytes (white blood cells) from blood components using special filters.

The Blood Service performs leucodepletion during the manufacturing of blood components via pre-storage leucodepletion which is performed either at the time of or soon after collection (for apheresis components) or within 48 hrs of collection (for whole blood derived components)

This is currently the standard international practice and Australia is therefore aligned with the many countries who similarly undertake leucodepletion.

The leucocytes present in donated blood play no therapeutic role in transfusion and may be a cause of adverse transfusion reactions. Removal of leucocytes may therefore have a number of potential benefits for transfusion recipients, including:

  • Reduced risk of platelet refractoriness
  • Reduced risk of febrile non-haemolytic transfusion reactions (FNHTR)
  • Reduced risk of CMV transmission
  • Reduction in storage lesion effect
  • Reduction in the incidence of bacterial contamination of blood components
  • Possible reduced risk of transfusion-associated graft vs host disease (TA-GVHD)
  • Possible reduction in transfusion related immunomodulatory (TRIM) effects, including cancer recurrence, mortality, non-transfusion transmitted infection
  • Possible reduced risk of transmitting variant Creutzfeldt-Jakob Disease (vCJD)

Leucocyte depletion may be performed before storage (at the blood collection centre) or after storage (in the hospital laboratory or at the bedside).

The optimum time to remove passenger leucocytes is before storage (called prestorage leucodepletion) for the following reasons:

  • Better process control and quality assurance

Leucocyte filtration is a complicated process that is influenced by factors such as the blood component’s prefiltration cellular composition and plasma content, the temperature of the blood component at the time of filtration, the filtration flow rate, the number of units transfused through the filter, and the timing of the filtration step.

Studies have documented a higher incidence of filtration failures when performed at the bedside as compared to leucocyte filtration performed in the laboratory setting.

Quality checks and comprehensive quality assurance programs can be more easily performed in the pre-storage setting. Bedside filtration also requires training of many nurses.

  • Lower incidence of febrile non-haemolytic transfusion reactions (FNHTR)

FNHTR are caused not only by leucocyte antigen-antibody reactions but also by the cytokines produced by leucocytes in the transfused blood component.

This would be more effectively prevented if the leucocytes were removed immediately after the blood is collected, avoiding the formation of cytokines.

This is especially the case with platelet components stored at room temperature as it has been demonstrated that cytokine production occurs more rapidly at 20 °C than 4 °C.

  • Lower incidence of alloimmunisation and (possibly) diminished immunomodulation that may result from the transfusion of membrane fragments

Leucocyte degradation during storage results in cell fragments which may not be removed by post-storage filtration and these can provoke HLA or platelet alloimmunisation.

Additionally, it is possible that leucocyte fragments released from cells harbouring leucotrophic viruses may carry such viruses through the filter.

  • Avoidance or reduction in the incidence of adverse effects directly related to the filtration process

Complications such as bradykinin-associated hypotension and transfusion related 'red eye' syndrome have been reported with particular types of filters used at the bedside.

  • Reduction in the incidence of bacterial contamination of blood components

Early removal of leucocytes (within 24 hours) may reduce the likelihood of significant bacterial contamination of red cells, particularly relating to Yersinia enterocolica and coagulase-negative Staphylococcus.

However, studies relating to bacterial growth in platelet components are much less convincing.

Leucodepletion of blood components removes ≥ 99% of contaminating leucocytes resulting in a reduction in the leucocyte count to less than 1 x 106per unit.

As part of the Blood Service’s routine quality monitoring procedures a percentage of leucodepleted components have their leucocyte count checked to ensure that the leucodepletion process is working properly and that these components are meeting specifications.

As the numbers of residual leucocytes in leucodepleted components are below the levels of detection of a standard haematology analyser, a more sensitive flow cytometric method has to be used for QC monitoring of the leucocyte count in these components.

All red cells and platelet components (both apheresis and pooled platelets) manufactured by the Blood Service are pre-storage leucodepleted, including red cell units of rare blood destined for freezing.

The leucodepletion system used by the Blood Service enables leucodepletion of some but not all clinical plasma. Whether clinical plasma is leucodepleted or not depends on the particular collection and/or manufacturing processes used in its production.

Consequently there is a mixed inventory of leucodepleted and non-leucodepleted clinical plasma components. Currently leucodepleted plasma components are not labelled as such.

The Blood Service does, however, strongly support universal leucodepletion of all blood components, including clinical plasma and plans to review the feasibility of moving to leucodepletion of 100% of clinical plasma in the future.

It is important to note that, should the Blood Service choose to introduce pathogen reduction or prion filtration, leucodepletion is a prerequisite for these technologies.

All autologous collections collected by the Blood Service are provided as leucodepleted autologous red cells. These have the same specifications as standard homologous leucodepleted red cells.

Pre-storage leucodepletion has been shown to reduce FNHTR.

Two mechanisms thought to cause FNHTR are cytokine release into stored blood components from contaminating white blood cells; and, the reaction of recipient antibodies with 'foreign' donor white blood cell antigens.

Therefore removal of white blood cells from blood components by leucodepletion provides a preventive measure against these two possible underlying causes of FNHTR.

As one of the benefits of pre-storage leucodepleted blood components is a reduction in FNHTR, fevers associated with transfusion of blood components should be carefully assessed to exclude complications such as bacterial contamination.

The reduction in HLA alloimmunisation as a result of leucodepletion of blood components, especially for multiple transfused patients and transplant recipients, is well established.

The level of leucodepletion we use is comparable to that achieved in the studies that have shown this benefit.

Leucocyte depleted components are considered to offer a high level of safety in preventing CMV transmission, but are not universally believed to be equivalent to CMV-seronegative components.

For indications where CMV negative blood components are required, the following is recommended:

  1. Select CMV-seronegative components whenever possible.
  2. If not available, leucocyte depleted components are considered to offer a high level of safety in preventing CMV transmission, but are not universally believed to be equivalent to CMV-seronegative components.
  3. Careful monitoring for CMV infection and disease in high risk patients.

The additional benefit of leucocyte depletion in preventing transfusion transmitted CMV infection, in the context of the sole use of CMV-seronegative components, is unknown.

Transfusion-associated graft versus host disease (TA-GVHD) is a rare complication of transfusion.

Gamma irradiation, which inactivates T-lymphocytes, is the main method of prevention and is indicated for all recipients considered to be at increased risk of TA-GVHD.

Leucodepletion does not provide the same protection and is not proven for this indication.

Since implementation of leucodepletion of 100% of red cells and platelets, bedside leucodepletion filters are no longer required.

Please note that all blood components still require administration via a standard blood administration set containing a 170–200 micron aggregate filter.

The blood components produced by the Blood Service already have over 99% of their leucocytes removed and so any additional reduction by bedside leucodepletion does not offer any benefit to the recipient.

Please note that all blood components still require administration via a standard blood administration set containing a 170–200 micron aggregate filter.
 

 

 

 

<< Previous page: Whole blood