Leukocyte Reduction

The Food and Drug Administration is expected to mandate the reduction of white blood cells, which has several benefits but which will significantly add to the cost of blood transfusions.

The Blood Products Advisory Committee (BPAC) of the FDA unanimously agreed in September 1998 that, from a scientific standpoint, the benefit-to-risk ratio of leukocyte reduction justifies universal leukoreduction of all non-leukocyte cellular blood components. A subsequent FDA workshop on December 10, 1999 gathered public input on a timetable for implementing universal leukoreduction and related issues.

The expected FDA mandate will significantly add to the cost of blood transfusions-we predict by between $30 and $40 per RBC unit. However, a number of research studies appear to indicate that hospitals may actually save money overall, e.g., by shortening length of stay and decreasing antibiotic usage. Further, studies have documented that leukocyte-reduced blood components can decrease febrile (fever) nonhemolytic transfusion reactions, HLA alloantibody formation, transmission of cytomegalovirus (CMV), and platelet transfusion refractoriness.

Febrile nonhemolytic (FNH) reactions are one of the most common, acute forms of a transfusion reaction. They cause morbidity for transfusion recipients, precipitate clinical and laboratory investigation of the cause of the reaction, may waste some units and usually delay transfusion therapy.

Many FNH reactions to blood components result from a recipient's immune recognition of donor leukocytes, and occur in individuals with prior sensitization to allogeneic (non-self) leukocyte antigens stimulated through pregnancy, transfusion or transplantation. Leukocyte reduction-whether performed before or after blood storage-is a highly effective means of preventing FNH reactions. ¹

Leukocyte reduction of allogeneic blood can decrease the incidence of HLA (tissue antigen) alloimmunization among patients with hematologic malignancy. ² This translates, for example, to fewer platelet refractory leukemia patients and less need for HLA-matched and/or crossmatch-compatible platelet transfusions.

CMV is a member of the herpes family of viruses and is associated with a spectrum of disease primarily affecting newborns and immunosuppressed individuals. Because CMV is highly cell-associated, leukocyte reduction is an effective strategy for preventing CMV transmission by transfusion.

Blood from donors who test negative for antibodies to CMV is also widely used to prevent transmission of CMV to at-risk recipients. ³

There is also some evidence to suggest that the rate of perioperative infections is less in patients undergoing surgical procedures requiring blood when leukoreduced components are used. ^4-7 If this is the case, the use of leukoreduced blood should lead to shorter hospital stays and significant reductions in antibiotic usage. Additionally, some studies suggest that cancer spread and recurrence are reduced by leukoreduced transfusions.

Pre-storage or Bedside Filtering
The most effective means of leukocyte reduction for RBC/whole blood is specific leukocyte filtering, either at the bedside during the transfusion or at the blood center shortly after collection (called "pre-storage leukoreduction").

In the June 2, 1999 issue of the Journal of the American Medical Association, the FDA alerted physicians and other health professionals to the potential for severe hypotensive reactions in patients receiving blood products transfused through a bedside leukocyte reduction filter. While the reaction, marked by a precipitous drop in patient blood pressure, is not common, the FDA recommended pre-storage leukocyte reduction in the blood collection center whenever feasible. More information on this notification can be found on the Internet at www.fda.gov/cdrh/safety.html.

Removing leukocytes from red blood cells and platelets at the blood center ensures consistent and effective leukoreduction. Another benefit to pre-storage filtering is the savings in time for hospital staff who will not have to set up (and monitor) the bedside leukoreduction filter, or wait for the blood to go through this additional filter.

Sacramento Medical Foundation's (SMF) Plan for Implementation
All plateletpheresis components provided by SMF and its blood centers have been leukoreduced since 1996. All SMF blood centers are increasing production of leukocyte-reduced red blood cells to meet orders from area hospitals. Physicians may wish to order all red cells as leukoreduced, or begin by requesting leukoreduced red blood cells for all patients currently being transfused through bedside leukoreduction filters.

We will continue our vigorous efforts, working at the national and state levels, to address the necessity of adequate funding for mandated safety initiatives like universal leukoreduction. In addition to efforts through America's Blood Centers, the American Association of Blood Banks, and the Blood Centers of California, I personally have met with our congressional staff representatives, and communicated with Dr. David Satcher, US Surgeon General, on these issues; I will continue to do so at every opportunity. Please call me, or any SMF physician, at (916) 456-1500 or (800) 995-4420 to discuss this matter further.

abotogo@ns.net

References
1. Parravicini A, Rebulla P, Apuzzo J, et al. The preparation of leukocyte-poor red cells for transfusion by a simple cost-effective technique. Transfusion 1984;24:508-9.
2. Klein HG, Dzik S, Slichter SJ, et al. Leukocyte-reduced blood components: Current status. Washington, DC: American Society of Hematology, 1998:39-62.
3. Smith DM, Lipton KS, Leukocyte reduction for the prevention of transfusion-transmitted cytomegalovirus. Association Bulletin #97-2. Bethesda, MD: American Association of Blood Banks, 1997.
4. Blajchman MA. Allogeneic blood transfusions, immunomodulation, and postoperative bacterial infection: Do we have the answers yet? (editorial) Transfusion 1997;37:121-5.
5. Vamvakas EC. Transfusion-associated cancer recurrence and postoperative infection: Meta-analysis of randomized, controlled clinical trials. Transfusion 1996;36:175-86.
6. Busch OR, HopWC, Hoynck van Papendrecht MA, et al. Blood transfusions and prognosis in colorectal cancer. N Engl J Med 1993;328:1372-6.
7. Van de Watering LMG, Hernans J, Houbiers JGA, et al. Beneficial effects of leukocyte depletion of transfused blood on postoperative complications in patients undergoing cardiac surgery: A randomized clinical trial. Circulation 1998;97:562-8.