Summary
This chapter reviews methods of production of leukocyte-depleted blood components, comments concerning the procedures used in the quality control of these products and a discussion of the proved and potential clinical benefits derived from the transfusion of these products in lieu of conventional white blood cell containing components. The advantages documented for the use of these products include a reduced incidence of nonhemolytic febrile transfusion reactions, a minimized rate of sensitization to HLA antigens and the accompanying immunological refractoriness to platelet transfusions and the provision of and a means to provide “cytomegalovirus” safe blood other than the traditional search for seronegative donors. The benefit of leukodepleted blood products in curtailing transfusion induced HTLV-I transmission, avoiding the immunomodulation which follows the receipt of blood and decreasing the rate of infection and tumor metastases which may be statistically associated with allogeneic blood transfusion are interesting possibilities that require prospective study. During the past three decades the technologies for the production of leukodepleted blood products have evolved from primitive procedures capable of removing less than 90% of the products’ native leukocytes to those that currently deplete −4 logl0 of the white cells. These techniques include sedimentation, centrifugation, cell washing, red cell freezing followed by deglycerolization, top and bottom component preparation systems and the use of laboratory and bedside filters. Although by definition not a leukocyte-depletion technique, ultraviolet irradiation of platelet concentrate has been recently shown to hold potential for reducing transfusion induced HLA sensitization. As the technologies to remove leukocytes from blood improve, so must the methods to qualify and monitor the production methods and products. At present the lower standard for leukodepleted components has been set at units containing no more than 106 white cells (U.S. standard, 5 x 106). Clinical studies may change these standards. Prototype filters are capable of now providing product containing as few as 103 leukocytes. The virtual elimination of all white cells from a blood component could conceivably justify new applications, such as products that lack the potential to elicit graft versus host disease.
The clinical use of leukocyte-depleted blood products (LDBP), specifically red cell (RCC) and platelet concentrates (PC), has dramatically increased in the past 10 years. A recent survey conducted by the College of American Pathologists (1993 CAP Surveys Set J-A) found approximately two-thirds of all facilities provide WBC reduced components to their clinical services and one-third of the responding institutions transfuse more than 10% of their cellular components as LDBP. The survey also confirmed that the majority of WBC reduced products are produced by filtration techniques. Improved efficiency and simplified production account for the increased use of LDBP. Increased use has led to numerous studies which confirm the clinical benefits derived from the use of these products.
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Keywords
- Blood Product
- Allogeneic Blood
- Platelet Concentrate
- Allogeneic Blood Transfusion
- Allogeneic Blood Product
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References
Perkins HA, Payne R, Ferguson J, Wood M. Nonhemolytic febrile transfusion reactions. Vox Sang 11: 578, 1966.
Kevy SV, Schmidt PJ, McGiniss MH, Workman WG. Febrile, nonhemolytic transfusion reactions and the limited role of leukoagglutinins in their etiology. Transfusion 2: 7, 1962.
Sirchia G, Parravicini A, Rebulla P, Fattori L, Milani S. Evaluation of three procedures for the preparation of leukocyte-poor and leukocyte-free red blood cells for transfusion. Vox Sang 38: 197, 1980.
Miner LV, Butcher K. Transfusion reactions reported after transfusion of red blood cells and of whole blood. Transfusion 18: 493, 1978.
Barret J, deLongh DC, Miller E, Litwin MS. Microaggregate formation in stored human red cells. Ann Surg 183: 109, 1976.
Swank RL. Alteration of blood on storage: measurement of adhesiveness of “aging” platelets and leucocytes and their removal by filtration. N Engl J Med 265: 728, 1970.
Solis RT, Gibbs MB. Filtration of the microaggregates in stored blood. Transfusion 25: 245, 1972.
Popovsky MA, Chaplin HC, Moore SB. Transfusion-related acute lung injury: a neglected, serious complication of hemotherapy. Transfusion 32: 589, 1992.
Doan CA. The recognition of a biological differentiation in the white blood cell. JAMA 86: 1593, 1926.
Kyger ER, Salyer KE. The role of donor passenger leukocytes in rat skin allograft rejection. Transplant 16: 53, 1973.
Perkins HA. HLA antigens and blood transfusion: effect on renal transplants. Transplant Proc 9 (Suppl 1): 229, 1977.
Meyers JD. Infection in recipients of marrow transplants. In. Remington JS, Swartz MN eds. Current Clinical Topics In Infectious Disease. New York: Mc Graw Hill, 261, 1985.
Hersman J, Meyers JD, Thomas JD, Buckner CD, Clift R. The effect of granulocyte transfusions upon the incidence of cytomegalovirus infection after allogeneic marrow transplantation. Ann Intern Med 96: 149, 1982.
Lang DJ, Ebert PA, Rodgers BM, Bogges HP, Rixse RS. Reduction of post transfusion cytomegalovirus infections following the use of leukocyte depleted blood. Transfusion 17: 391, 1977.
Sato H, Okochi, K. Transmission of human T-cell leukemia virus (HTLV-I) by blood transfusion: demonstration of proviral DNA in recipients blood lymphocytes. Int J Cancer 37: 395, 1986.
Baird MA, Bradley MP, Helsop BF. Prolonged survival of cardiac allografts in rats following the administration of heat treated donor lymphocytes. Transplant 42: 1, 1986.
Blajchman MA, Bardossy L, Carmen R, Sastry A, Dharam PS. Allogeneic blood transfusion-induced enhancement of tumor growth: two animal models showing amelioration by leukodepletion and passive transfer using spleen cells. Blood 81: 1880, 1993.
Waymack JP, Robb E, Alexander JW. Effects of transfusion on immune function in a traumatized animal model. Arch Surg 122: 935, 1987.
Jensen LS, Andersen AJ, Christansen PM, Hokland P, Juhl CO, Madsen G, Mortensen J, Mailer-Nielsen C, Hanberg-Sorensen F, Hokland M. Postoprative infection and natural killer cell function following blood transfusion in patients undergoing elective colorectal surgery. Br J Surg 79: 513, 1992.
Tartter PI. Blood transfusion and infectious complications following colorectal cancer surgery. Br J Surg 75: 789, 1988.
Blumberg N, Triulzi DJ, Heal JM. Transfusion-induced immunomodulation and its clinical consequences. Transf Med Rev 4: 24, 1990.
Wenz B. Leukocyte-poor blood. CRC critical reviews in laboratory sciences 24: 1, 1985.
Wenz B, Apuzzo J. Removal of micro-aggregates from blood using various filters. Transfusion 24: 88, 1984.
Geerdink P. “Why filter blood?” Leukocyte Poor Blood-Recent Developments. Dublin, Ireland, April, 1984.
Lieden G, Hilden JO. Febrile transfusion reactions reduced by the use bully-coat-poor erythrocyte concentrates.Vox Sang 43: 263, 1982.
Wenz, B. Leukocyte free red cells: The evolution of a safer blood product. in. McCarthy L.J. and Baldwin ML, eds. Controversies of leukocyte poor blood. Arlington, VA. AABB, 1989.
Bowden RA, Slichter SJ, Sayers MH, Mori M, Cays MJ, Meyers JD. Use of leukocyte-depleted platelets and cytomegalovirusseronegative red blood cells for prevention of primary cytomegalovirus infection after marrow transplant. Blood 78: 246, 1991.
Wenz B, Besso N. Quality control and evaluation of leukocyte depleting filters. Int Workshop on the Role of Leucocyte Depletion in Blood Transfusion Practice. July 1988; London, U.K.
Wenz, B., Burns, E.R., Lee, V. and Miller, W.K. A rare event analysis model for quantifying white blood cells in leukocyte depleted blood. Transfusion 31: 156, 1991.
Pollack W, Reckel RP. The zeta potential and hemagglutination with Rh antibodies. Int Arch Allergy 38:: 482, 1970.
Pollack W, Hager HJ, Hollenbeck LL. The specificity of anti-human gamma globulin reagents. Transfusion 2: 17, 1962.
Cassel. M, Phillips DR, Chaplin H Jr. Transfusions of buffy coat-poor suspensions prepared by Dextran sedimentation. Description of newly designed equipment and evaluation of its use. Transfusion 2: 216, 1962.
Chapel H Jr, Brittingham TE, Cassel M. Methods for preparation of suspensions of buffy coat-poor red cells for transfusion. Am J Clin Path 31: 373, 1959.
Polesky HF, McCullough J, Helgeson MA, Nelson C. Evaluation of methods for the preparation of HLA antigen poor blood. Transfusion 13: 383, 1973.
Uda M, Naito S, Yamamoto K, Ishii A, Nishizaki T. Optimal protocol for preparation of leukocyte-poor red cells with a blood cell processor. Transfusion 24: 120, 1984.
Bijou H, Brady MT, Fortes P, Hawkins EP. Inconsistent leukocyte removal by IBM 2991 blood cell processor. Transfusion 23: 260, 1983.
Luyet BJ. Ultra rapid freezing as a possible method of blood preservation. in; Preservation of the formed elements and of the proteins of the blood. ARC. Wash DC. 141, 1959.
Meryman HT, Hornblower M. Quality control of deglyceolized red blood cells. Transfusion 211: 235, 1981.
Crowley JP, Wade PH, Wish C, Valeri CR. The purification of red cells for transfusion by freeze-preservation and washing. V. Red cell recovery and residual leukocytes after freeze-preservation with high concentrations of glycerol and washing in various systems. Transfusion 17: 1, 1977.
Diepenhorst P, Sprokholt R, Prins HK. Removal of leukocytes from whole blood and erythrocyte suspensions by filtration through cotton wool. I. filtration technique. Vox Sang. 23: 308, 1972.
Reesink HW, Veldman H, Henrichs HJ, Prins HK, Loos JA. Removal of leukocytes from blood by fibre filtration. Vox Sang 42: 281, 1982.
Wenz B, Burns ER. Phenotypic characterization of white cells in white cell-reduced red cell concentrate using flow cytometry. Transfusion 31: 829, 1991.
Rebulla P, Porretti L, Bertolini F, Marangoni F, Prati D, Smacchia C, Pappalettera M, Parravicini A, Sirchia G. White cell-reduced red cells prepared by filtration: a critical evaluation of current filters and methods for counting residual white cells. Transfusion 33: 128, 1993.
Barret J, deLongh DC, Miller E, Litwin MS. Microaggregate formation in stored human red cells. Ann Surg 183: 109, 1976.
Wenz B. Microaggregate blood transfusion and the febrile transfusion reaction. A comparative study. Transfusion 23: 95, 1983.
Parravicini AM, Rebulla P, Apuzzo J, Wenz B, Sirchia G. The preparation of leukocyte-poor red cell for transfusion by a simple, cost effective technique. Transfusion 24: 508, 1984.
Sirchia G., Wenz B, Rebulla P, Parravicini A, Carnelli A and Bertolini F. Removal of leukocytes from red blood cells by transfusion through a new filter. Transfusion 30: 30, 1990.
Steneker I, Prins HK, Florie M, Loos JA, Biewenga J. Mechanisms of white cell reduction in red cell concentrates by filtration: the effect of the cellular composition of the red cell concentrates. Transfusion 33: 42, 1993.
Callaberts AJ, Gielis ML, Spengers ED, Muylle L. The mechanism of white cell reduction by synthetic fiber cell filters. Transfusion 33: 134, 1993.
Wenz B. and Besso, N. Automated vs microscopic chamber counts for leukocyte depleted blood. International workshop on the role of leucocyte-depleted blood products.In. The role of leucocyte depletion in transfusion practice. Proceedings of the international workshop. Ed. Brozovic. Blackwell Scientific Publications. London, U.K.
Lindahl-Kiessling K, Safwenberg J. Inabil ity of UV-irradiated lymphocytes to stimulate allogeneic cells in mixed lymphocyte culture.Int Arch Allergy Appl Immunol 41: 670, 1971.
Stingl G, Gazze-Stings LA, Aberer W, Wolff K. Antigen presentation by murine epidermal Langerhans cells and its alteration by ultraviolet light. J Immunol 127: 1707, 1981.
Gruner S, Meffert H, Karasek E, Sonnichsen N. Prolongation of skin graft survival in mice by in vitro PUVA treatment and failure of induction of specific immunologic memory By PUVA treated grafts. Arch Dermatol Res 276: 82, 1984.
Deeg HJ, Aprile J, Graham TC, Applebaum FR, Sorb R. Ultraviolet irradiation of blood prevents transfusion-induced sensitization and marrow graft rejection in dogs. Blood 67: 537, 1986.
Slichter SJ, Deeg HJ, Kennedy MS. Prevention of platelet alloimmunization in dogs with systemic cyclosporine and by UV-irradiation of or cyclosporine-loading of donor platelets. Blood 69: 414, 1987.
Sherman L, Menitove J. Kagen LR, Davisson W Lin A, Aster RH, Buchholz DH. Ultraviolet-B irradiation of platelets: a preliminary trial of efficacy. Transfusion 32: 402, 1992.
Johnson RB, Napychank S, Murphy S, Snyder EL. In vitro changes in platelet function and metabolism following increasing doses of ultraviolet-B irradiation. Transfusion 33:249, 1993.
Valerie K, Delers A, Bruck C, et al. Activation of human immunodeficiency virus type 1 by DNA damage in human cells. Nature 333: 78, 1988.
Cornforth MN, Bedford JS. On the nature of a defect in cells from individuals with ataxia-telangiectasia. Science 227: 1589, 1985.
Emerson SG, Pretell G, Cone RE. Physical and pharmacologic inhibition of shedding of I-A antigens. Exp Clin Immunogenet 1: 9, 1984.
Pernis B. Internalization of lymphocyte membrane components.Immunol Today 6: 45, 1985.
Price TH, Ford SE, Northway MM. Alternate collection protocols for plateletpheresis using the Cobe Spectra. American Soc Apheresis, April, 1989; A61.
Shanwell A, Gullickson H, Berg BK, et al. Evaluation of platelets prepared by apheresis and stored for 5 days. In vitro and in vivo studies. Transfusion 29:783, 1989.
Sniecinski I, Nowicki B, Park HS, et al. Platelet yields and leukocyte contamination of plateletpheresis concentrates: Comparison of three continuous flow systems. 4th Int Cong World Apheresis Assoc. Saporo, Japan. June A174, 1992.
Kretschmer V, Rossa W, Eisenhardt G. Plateletpheresis with the new Cobe-Spectra. American Soc for Apheresis. 116 Annual Meeting, San Francisco, CA. March A72, 1990.
Rock G, Senack E, Tittley P. 5-day storage of platelets collected on a blood cell separator. Transfusion 29: 626, 1989.
Anderson NA, Wilkes A, Smith H, et al. Platelet collection using the Cobe Spectra and Haemonetics V50 Autosurge with identical donors. 3rd Int Cong World Apheresis Association, Amsterdam, Netherlands. April, 1990; WE-PO-E.
Hogman CF, Eriksson L, Hedlund K, Wallvik J. The top and bottom system: A new technique for blood component preparation and storage. Vox Sang 55: 211, 1988.
Pietersz RNI, Dekker WJA, Reesink HW. Comparison of a conventional quadruple-bag system with a ‘top-and-bottom’ system for blood processing. Vox Sang 59: 205, 1990.
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Wenz, B. (1995). Methods of Leukodepletion. In: Clinical Benefits of Leukodepleted Blood Products. Medical Intelligence Unit. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-26538-3_2
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