FAQ: Blood Center

Answer 1:

Leukocytes are unnecessary contaminants in unfiltered blood products and have been reported to be responsible for a variety of adverse reactions, including:

• Alloimmunization, which may lead to platelet refractoriness if multiple and/or subsequent transfusions are required.¹
• Febrile non-hemolytic transfusion reactions (FNHFTR)²
• Immunosuppression^3,4 which may contribute to an increased incidence of postoperative infections^5,6 and tumor recurrence^7,8
• Transmission or reactivation of intracellular viruses (i.e., cytomegalovirus [CMV] and human T-cell lymphotropic virus type I [HTLV-I] ^9,10 The increased incidence of morbidity, as well as the high costs associated with transfusion complications, has led to the development of filters to reduce leukocytes in cellular blood components. Leukocyte reduction has been demonstrated to be clinically effective in reducing the incidence of these transfusion-related complications, including post operative infections^5,6 which can significantly decrease the cost of medical care^4,11,12 for these patients, producing significant cost reduction to hospitals annually. Today leukocyte reduction may be easily accomplished in any blood center or hospital situation.

Answer 2:

Leukocyte reduction filters differ from manufacturer to manufacturer in their white blood cell reduction efficiency, performance and consistency. In addition, different leukocyte reduction technologies produce different residual white blood cell subsets and biochemical end products¹⁴ . Pall Purecell^® High Efficiency Leukocyte Reduction filters and Leukotrap^® systems have been clinically demonstrated to produce a highly specific blood product that dependably and consistently provides the lowest residual leukocyte levels. These differences separate Pall technology from other manufacturers. Pall filtration technology has been the choice of researchers in most of the milestone clinical studies published on leukocyte reduction.

Answer 3:

Yes, Pall offers products for both neonatal and pediatric transfusions. These can be used on non-leukoreduced blood components that have been aliquoted. Some clinicians may consider using these products for previously leukoctye reduced components to assure as cell free a transfusion as possible for their neonatal and pediatric patients.

Answer 4:

The first method of leukocyte reduction occurred at the bedside. Pall's full array of products, which includes the Purecell^® line of products is still available for customers currently relying on bedside leukocyte reduction or for clinicians seeking as cell free a product as possible for previously leukocyte reduced components. In recent years as the use of leukocyte reduction and its applications have grown, particularly with the movement toward universal leukocyte reduction, performing the leukocyte reduction process under controlled laboratory conditions assuring maximum WBC reduction efficiency has become the preferred option for many customers. With this process having been validated by the blood center, the reduction efficiency is documented. Decisions about when and where to leukocyte reduce at the present are based on geographic standards, cost considerations and other factors.

Answer 5:

The BC has a number of options including a combination of Pall Leukotrap^® inline and dockable blood processing filtration systems. These systems include a four-log white blood cell (WBC) reduction filter that consistently produces leukoreduced red blood cells (RBCs) with average post-filtration WBC counts <1x10⁶ (one million), well below the < 5x10⁶ (five million) required by the American Association of Blood Banks (AABB). There is also a filter available for pre-storage leukocyte reduction of platelet rich plasma during component processing to make a prestorage leukocyte reduced platelet concentrate.

Answer 6:

Pre-storage leukoreduction is usually performed during the first 24-48 hours after blood donation, following the completion of all required tests or as part of component processing. Even in those instances where delays occur, or special antigen-negative blood is required, pre-storage leukoreduction is usually completed before day five of storage. Leukocyte reduction with Pall's RBC dockable filter systems can be done within 5 days of collection (perferably within 3 days) and at the bedside can be done at any time in the storage life of the blood or platelet component.

Answer 7:

Yes. When leukocytes are allowed to remain with RBCs during storage, they release potentially harmful degradation or breakdown products, including histamine, cytokines and HLA membrane fragments. Many researchers have linked these biological response modifiers to adverse transfusion reactions especially in platelets.

Answer 8:

Performing the leukoreduction process under controlled laboratory conditions assures maximum WBC reduction efficiency. Furthermore, the process has been validated by the blood center and/or transfusion service so that reduction efficiency is documented.

Answer 9:

The recommended FDA guideline¹⁷ for QC sampling is as follows:

• 1% of the blood center’s monthly production of each leukocyte reduced blood component, or
• 4 units per month for those blood centers that produce less than 400 leukoreduced units per month¹.

Answer 10:

Modern filtration technology reduces 100 to 1000 times the number of leukocytes as compared to the washing or deglycerolization processes. The AABB has recognized this in their Blood Transfusion Therapy, A Physician’s Handbook, 5^th edition¹⁵:

…using washed RBCs for this purpose alone [leukoreduction] is no longer justifiable, [and] … modern leukocyte-reduction filters have supplanted the use of this component [frozen deglycerolized cells] for this purpose.

In addition, the cost of leukoreduced RBCs is typically lower than for either washed or deglycerolized blood.

Answer 11:

No. Since the blood processing/filtration systems used for leukoreduction are closed, standard 35 or 42-day outdating of filtered RBCs is maintained depending on the use of CPDA1 or additive.

Answer 12:

The blood center is encouraged to examine the literature and develop an appropriate policy covering this issue. However, some blood centers have already taken steps to offer hospitals leukoreduced blood components as an alternative to CMV screening, supported by several published studies. One in particular compares the effectiveness of blood components leukoreduced by filtration to CMV-seronegative screened blood products¹⁰. The results demonstrate that filtered blood components may reduce the incidence of transfusion-transmitted CMV infection in marrow transplant patients. Only Pall High Efficiency Leukocyte Reduction Filters were used in this study.

Answer 13:

Yes, blood components that are leukocyte reduced in the laboratory must be transfused through a blood administration set containing a standard (170-micron) clot screen, in order to remove blood clots and other debris¹⁵. The Pall SQ40 product family offers a cost effective solution for filtration by minimizing administration set change typically encountered when more than one unit of blood is administered.

Answer 14:

Yes, we believe you can. While there is usually an additional fee for leukoreduced blood components, the hospital may not be aware of the hidden costs associated with leukoreduction at the bedside. These costs include the staffing involved to purchase and inventory filters (occasionally more than one filter per unit when flow rate problems are encountered), nursing and/or medical technician time, and RBC loss due to filter hold-up. In addition, it is important to remember that QC is difficult or impossible to perform at the bedside, and that the cost of failing to prevent WBC-related complications is substantial.

Answer 15:

To date, there are no published data on the advantage of leukoreduction of autologous RBC units. The autologous leukocytes would obviously not immunize the patients to any foreign HLA antigen. However, the release of leukocyte breakdown products – cytokines, etc. in stored RBC units may result in adverse reactions even in the recipient of autologous units.

Answer 16:

The adoption of universal leukocyte filtration to improve the safety of the blood supply is an emerging trend throughout the world. To date, a number of countries within Europe (France, Austria, Finland, Ireland, Portugal, United Kingdom), as well as Canada, have introduced national programs to implement this practice as a standard of care.

On September 18, 1998, the FDA’s Blood Products Advisory Committee (BPAC) recommended that "the benefit to risk ratio associated with leukoreduction is sufficiently great to justify routine leukoreduction of all non-leukocyte transfusion blood components…"¹⁸.

Answer 17:

While leukocyte reduced blood components have often been reserved as a special product for special patients (oncology/hematology, dialysis, newborn/pediatric, HIV+, solid organ and bone marrow transplant, etc.), a growing number of U.S. hospitals are now leukocyte reducing all the blood components they use. This is due to growing evidence supporting the benefits of leukocyte reduction for transfused surgery patients, the BPAC recommendation (See Question 12) and the growing number of countries moving toward or already leukocyte reducing their entire blood supply such as Canada, the United Kingdom, Ireland, France, Portugal, Austria and Finland.

1. The Trial to Reduce Alloimmunization to Platelets Study Group. Leukocyte-reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions. N Engl J Med 1997; 337:1861-9.
2. Lane TA, Anderson KC, Goodnough LT, et al. Ann Intern Med. 1992;117:151-162.
3. Triulzi DJ, Vanek K, Ryan DH, et al. Transfusion. 1992;32:517-524.
4. Jensen LS, Andersen AJ, Christiansen PM, et al. Br J Surg. 1992;79:513-516
5. Heiss MM, Mempel W. Delanoff, C, et al. J Clin Oncol. 1994; 12(9): 1859-1867
6. Blumberg N, Agarwal MM, Chuang C. Br Med J. 1985; 290: 1037-1039
7. Busch MP, Lee T-H. Clinical Benefits of Leukodepleted Blood Products. Austin, TX: RG Landes Co; 1994
8. Sayers MH, Anderson KC, Goodnough LT, et al. Ann Intern Med. 1992; 116(1): 55-62
9. de Graan-Hentzen YCE, Gratama JW, Mudde GC, et al. Transfusion. 1989; 29:757-760
10. Bowden RA, Slichter SJ, Sayers M, et al. Blood 1995; 86: 3598-3603
11. Blumberg N, Heal JM, Kirkley SA, et al. American Journal of Hematology 1995; 48:108-115.
12. Sniecinski I. The impact of leukocyte reduced blood components on the cost of transfusion therapy in bone marrow transplantation. Presented at the 1993 Annual Meeting of the American Association of Blood Banks in Miami, FL.
13. Higgins, Virginia L. Leukocyte-Reduced Blood Components: Patient Benefits and Practical Applications Oncology Nursing Forum Vol. 23, No. 4, 1996 pp 659-667
14. Sowenimo-Coker, S.O., Kim, A., Tribble, E., Brandwein, H.J., Wenz, B.: White cell subsets in apheresis and filtered platelet components, Transfusion 1998; 38: 650-657
15. Blood Transfusion Therapy ? A Physician's Handbook 5th Edition by AABB, 1996
16. Technical Manual: 12th Edition by AABB, 1996 p.456
17. Food and Drug Administration Department of Health & Human Services.Recommendations and licensure requirements for leukocyte-reduced blood products. Memorandum to all registered blood establishments; May 29, 1996
18. U.S. Department of Health & Human Services, Blood Products Advisory Committee (BPAC) meeting: 1998, #60