Leucodepletion of Red Cells and Platelets FAQs
What change is ARCBS introducing?
The Australian Red Cross Blood Service (ARCBS) is introducing nationwide pre-storage leucodepletion of red cell components. This will bring red cell components in line with platelet components which have been leucodepleted nationally since April 2008.
The timetable for implementation of pre-storage leucodepletion of 100% of red cells is as follows:
• 1 July 2008 - Western Australia, South Australia, Victoria and Tasmania.
• 1 October 2008 - New South Wales and Queensland.
Northern Territory implemented 100% red cell leucodepletion in July 2006 and the Australian Capital Territory in January 2008.
It should be noted that there will be a 42 day period following implementation when laboratories may receive a mixed inventory comprising of both leucodepleted and non-leucodepleted red cells. All leucodepleted red cell components will be labelled as such. During this period, bedside leucodepletion may need to continue for non-leucodepleted red cell components if clinically indicated.
Why is this change occurring?
This change is occurring because ARCBS has now received funding from Government through the National Blood Authority (NBA) following the submission of a business case.
Leucodepletion of blood components has become the international standard of practice. In implementing this change, Australia will be aligning its practice with the many countries who have already adopted leucodepletion.
How was this decision made?
ARCBS submitted a business case to the NBA to allow consideration of the benefits and funding requirements for implementation of pre-storage leucodepletion of 100% of red cells and platelets. The business case was given in principle approval by the Australian Health Ministers’ Conference (AHMC) in March 2007 and was subsequently formally approved at the AHMC April 2008 meeting.
Does the Australian Red Cross Blood Service (ARCBS) already leucodeplete some blood components?
All platelet components (i.e. both pooled and apheresis platelets) distributed by ARCBS have been leucodepleted since April 2008.
Prior to 1 July 2008, the percentage of red cells that were pre-storage leucodepleted was significantly lower with some variation between jurisdictions.
If some jurisdictions are changing ahead of others, what will happen if components are shipped interstate?
Shipping of non-leucodepleted blood components to jurisdictions with 100% leucodepletion will be avoided if at all possible. However, this may be necessary to meet special product requirements (for example, rare blood group or phenotyped blood). In such situations, an ARCBS Transfusion Medicine Specialist will discuss the available options with the treating clinician concerned.
What are the benefits of leucodepletion?
Leucodepletion is the removal of white blood cells from a blood component.
The potential benefits of leucodepletion for patients include:
• Reduction in platelet refractoriness;
• Reduction in febrile non-haemolytic transfusion reactions;
• Reduction in CMV transmission risk;
• Improved chance of finding an organ transplant match if required;
• Reduction in storage lesion effect;
• Possible reduction in transfusion associated graft vs host disease (TA-GVHD) risk;
• Possible reduction in transfusion related immunomodulatory effects, including cancer recurrence, mortality, non-transfusion transmitted infection; and
• Possible reduction in variant Creutzfeldt-Jakob Disease (vCJD) transmission risk.
What are the benefits of pre-storage leucodepletion compared with bedside leucocyte depletion?
Leucocyte depletion may be performed before storage (at the blood collection centre) or after storage (in the hospital laboratory or at the bedside). There is little doubt that the optimum time to remove passenger leucocytes is before storage (called pre-storage 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 pre-filtration 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.
What will be the level of leucocyte depletion?
Leucodepletion of blood components will result in a reduction in the leucocyte count to less than 1 x 106 white cells per unit.
Will every component be below this level?
This level of leucodepletion will apply to whole blood, red cells and platelets. Routine quality control will be performed to ensure that the process is meeting these specifications.
Is the leucodepletion by ARCBS performed pre-storage or later on?
Leucodepletion will be performed pre-storage. This will be either at the time of or soon after collection (for apheresis components) or within 48 hours of collection (for whole blood derived components).
Will the leucodepletion process mean it will take longer for ARCBS to issue each component?
Leucodepletion will not affect the time between collection and availability for issue of the various components.
What will happen if I need to access a blood component urgently?
The process of leucodepletion should not affect the time to access blood components, which is also dependent on other processing and testing requirements.
Will all components be leucodepleted?
All red cells and platelet components will be leucodepleted.
What about fresh frozen plasma (FFP), cryoprecipitate and cryo-depleted plasma?
The leucodepletion system that is to be implemented by ARCBS will enable some leucodepletion of clinical plasma as a consequence of one of the manufacturing processes for leucodepleted red cells. However, not all clinical plasma will be leucodepleted.
There will, therefore, be a mixed inventory of leucodepleted and non-leucodepleted clinical plasma components. Leucodepleted plasma components will not be labelled as such.
ARCBS does, however, strongly support universal leucodepletion of all blood components, including clinical plasma. Following implementation of leucodepletion of 100% of red cells and platelets, ARCBS plans to review the feasibility of moving to leucodepletion of 100% of clinical plasma.
It is important to note that, should ARCBS move forward some time in the future either with pathogen reduction or prion filtration, leucodepletion is a mandatory prerequisite for these technologies.
What about whole blood?
Fresh unrefrigerated whole blood will be leucodepleted prior to issue. As of 1 July 2008, cold stored whole blood, including autologous whole blood, will no longer be supplied by ARCBS.
If whole blood is leucodepleted, will this affect its platelet content?
Leucodepletion of whole blood will be performed using a “platelet-conserving” filter. This will minimise the loss of platelets during the filtration process.
Will autologous collections also be leucodepleted?
As part of the ARCBS move to 100% leucodepletion of red cells, all autologous collections will be provided as leucodepleted autologous red cells with the same specifications as homologous red cells.
Autologous whole blood will no longer be supplied. As autologous whole blood is stored, it does not offer additional benefits in terms of its plasma or platelet fractions. In addition, the provision of autologous red cells enables a longer storage time (42 days) as compared with whole blood (35 days).
What about components manufactured prior to the introduction of leucodepletion, for example frozen units of rare blood?
In such situations, an ARCBS Transfusion Medicine Specialist will discuss the available options with the treating clinician concerned.
Frozen red cells are prepared by adding glycerol to red cells as a cryoprotective agent before freezing. The glycerol must be removed from the thawed component by washing the cells with sodium chloride before it is infused. This washing process does render the red cells substantially leucocyte reduced.
All future collections of red cells destined for freezing will be pre-storage leucodepleted.
Will the level of leucodepletion prevent my patient getting febrile non-haemolytic (FNH) reactions?
Prestorage leucodepletion has been shown to reduce FNH transfusion reactions.
The two main mechanisms thought to cause FNH reactions include cytokine release by contaminant white cells into stored blood components and recipient antibodies reacting with foreign donor white blood cell antigens.
Leucodepletion of blood components within 24 hours of collection results in a reduction in the white blood cells present to react with recipient antibody and a reduction in cytokine release into the blood component, thereby ameliorating the two main mechanisms of FNH reactions.
As one of the benefits of pre-storage leucodepleted blood components is a reduction in FNH transfusion reactions, fevers associated with the transfusion of such a component should be carefully assessed to exclude complications such as bacterial contamination.
Will the level of leucodepletion prevent my patient becoming alloimmunised and/or refractory to platelet transfusions?
The reduction in HLA alloimmunisation as a result of leucodepletion of blood components, especially for multiply transfused patients and transplant recipients, is well established. The level of leucodepletion used by ARCBS is comparable to that achieved in the studies that have shown this benefit.
Does the leucodepletion process mean that there will no longer be a need for CMV negative blood components?
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.
Will red cells and platelets still need to be irradiated?
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.
Does this mean that my hospital no longer needs to buy leucodepletion filters?
All blood components will still require administration via a standard blood giving set containing a 170-200 micron aggregate filter. Bedside leucodepletion filters will no longer be required once leucodepletion of 100% of red cells and platelets is fully implemented.
Would it be even safer if I still use a bedside leucodepletion filter?
All blood components will still require administration via a standard blood giving set containing a 170 – 200 micron aggregate filter. Bedside leucodepletion will not provide any further reduction in the leucocyte content of blood components and, therefore, will not provide any additional benefit to pre-storage leucodepletion.
As a transfusion nurse or a clinical nurse manager what should I do?
Talk to clinical areas about the change and reinforce that further bedside leucodepletion is not required. All blood components will still require administration via a standard blood giving set containing a 170 – 200 micron aggregate filter.
Put a reminder (e.g. poster) in the spot where the leucodepletion filters used to be stored to remind staff they are no longer required.
Liaise with your supply department to ensure that bedside leucodepletion filters are not ordered.
Review your hospital’s policies and procedures relating to transfusion practice to remove references to bedside leucodepletion.