EDITORIAL The abandoned controversy surrounding universal white blood cell reduction Eleftherios C. Vamvakas Los Angeles, CA, United States of America
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Notwithstanding the uncertainty about what the USA ICER might be, the study by Tsantes et al.2 raises the question of whether the policy of implementing universal WBC reduction needs to be reconsidered. In 1999, the United Kingdom, Ireland, and Portugal implemented universal WBC reduction of all transfused cellular blood components based on the hypothesis that this intervention might prevent transmission of the agent of variant Creutzfeldt-Jakob disease (vCJD). In North America, there was considerable debate about the appropriateness of introducing universal WBC reduction to prevent the purported adverse effects of allogeneic blood transfusion-related immunomodulation (TRIM)3. In the end, Canada implemented universal WBC reduction but the USA did not, and the proportion of WBC-reduced components transfused by hospitals in the USA today reflects local availability more than clinical preference. More specifically, hospitals in the USA use WBC-reduced components either universally or selectively, depending primarily on their location and the practice of the local blood provider (which may manufacture only leucoreduced or both leucoreduced and non-leucoreduced cellular blood components). Allogeneic blood transfusion results in numerous immunological alterations which may represent mere laboratory curiosities or may reflect some clinically relevant aberration in the recipient's immune function —the so-called "immunomodulatory" effect— of the allogeneic transfusion. The acronym TRIM was initially introduced to designate the constellation of allogeneic blood transfusion-associated laboratory alterations as well as clinical effects (enhanced survival of renal allografts, increased recurrence rate of resected malignancies, increased incidence of post-operative bacterial infections, and activation of endogenous cytomegalovirus and human immunodeficiency virus infection) that could be attributed to allogeneic blood transfusion by immunological mechanisms. More recently, the term has been used more broadly, to encompass additional effects that could be related to allogeneic blood transfusion by means of both immunomodulatory as well as pro-inflammatory mechanisms. Pro-inflammatory, and other poorlyunderstood, effects of allogeneic blood transfusion have been invoked to explain, for example, the association
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Proven benefits from white blood cell (WBC) reduction can be secured through selective removal of leucocytes from cellular blood components destined for transfusion to specific categories of patients, that is, patients with a history of febrile, non-haemolytic transfusion reactions (FNHTRs), patients at risk of platelet refractoriness because of receipt of multiple platelet transfusions, and patients at risk of cytomegalovirus disease1. In the absence of considerations of cost, universal leucoreduction of all transfused cellular blood components could extend to all patients these three proven benefits of WBC reduction. Although patients who have not suffered from a FNHTR, are not receiving long-term platelet transfusions, and are not at risk of developing cytomegalovirus disease may derive no immediate benefit from WBC reduction, it is possible that these patients may accrue some tangible benefit in the future. As regards specifically FNHTRs, patients may also accrue some tangible benefit from universal WBC reduction also in the present, because any patient receiving a non-leucoreduced cellular blood component is at risk of developing a FNHTR. It is for this reason that Tsantes et al.2, in this issue of Blood Transfusion, report on the cost-effectiveness of universal WBC reduction for preventing FNHTRs. Among patients transfused with 86,032 units of red blood cells, 0.411% of the recipients of non-WBC-reduced units, compared with 0.047% of the recipients of WBC-reduced units, developed a FNHTR. In Greece, where the study was conducted, the cost of preventing one FNHTR (i.e., the incremental cost-effectiveness ratio [ICER] of € 6,916 or US$ 9,438) was deemed not to be cost-effective by the authors. Nonetheless, the risk of developing FNHTRs was indeed reduced by WBC reduction. Moreover, the calculated ICER and the judgment about whether universal WBC reduction is cost-effective depend, respectively, on the setting in which costs are estimated and the ratio of the calculated ICER to the average cost of a hospitalisation during which a red blood cell transfusion is administered. An ICER of US$ 9,438 might be deemed by some to be cost-effective for the prevention of FNHTRs in at least some US settings, although the cost estimates that resulted in the calculation of this particular ICER in Greece are not directly transferrable to the USA. Blood Transfus 2014; 12: 143-5 DOI 10.2450/2014.0009-14 © SIMTI Servizi Srl
143 All rights reserved - For personal use only No other uses without permission
Vamvakas EC
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reduction. Doing so would divert attention from our efforts to reduce other, proven risks of allogeneic blood transfusion. Transfusion-related acute lung injury21, mistransfusion, and bacterial contamination of platelets22 likely remain among the top proven, but not yet fully addressed, risks of blood transfusion23. Since all residual risks of blood transfusion cannot be dealt with simultaneously, policy-makers must carefully select which risk to confront next, so as to accrue the greatest possible societal gain in terms of improved transfusion safety. The greatest "competing risk" when a new safety measure is implemented is what other possible safety improvement(s) is/are left behind, because public resources and attention have been directed to the measure that has been selected for focused debate and/or implementation24. Given the competing risks of TRALI, mistransfusion, and bacterial contamination of platelets, and as also indicated by the cost-effectiveness study of Tsantes et al.2, the most effective way of expending public resources to improve transfusion safety would not be the implementation of universal WBC reduction in regions or countries in which universal WBC reduction has not yet been introduced. The Author declares no conflict of interest.
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between allogeneic blood transfusion and increased short-term (up to 3 month post-transfusion) mortality. Twelve randomised controlled trials4-15 comparing subjects randomised to receive non-WBC-reduced vs WBC-reduced allogeneic red blood cells or whole blood and investigating the development of bacterial infection were reported between 1992 and 2005. Eleven randomised controlled trials5,7-13,15-17 reported on shortterm (up to 3-month post-transfusion) mortality from all causes. With regard to bacterial infection, estimates of the TRIM effect have varied from a 7.3-fold increase in the risk of post-operative infection in association with the receipt of non-WBC-reduced (vs WBC-reduced) allogeneic blood transfusion4 to no effect from the transfusion8-15. With the sole exception of the randomised controlled trial by Bilgin et al.7 in the context of cardiac surgery, all randomised controlled trials conducted in the 21st century9-13,15 have consistently produced negative findings. With respect to all-cause, short-term mortality, all studies produced negative findings with the exception of two randomised controlled trials in cardiac surgery8,13. Across all cardiac-surgery studies7,8,11,13,15, there was a 72% increase in mortality in association with nonleucoreduced (compared with leucoreduced) products in the context of allogeneic blood transfusion18. This result conforms with what would have been expected from the immunomodulation theory (that there would be more of a TRIM effect in cardiac surgery, in which the pro-inflammatory effect of the extracorporeal circuit acts as a co-factor, than in other settings19); and it is the only statistically valid and clinically meaningful adverse TRIM effect detected from the 14 available randomised controlled trials4-17. Thus, the comprehensive study of the purported adverse TRIM effects by means of randomised controlled trials added a fourth indication to the three established indications for WBC reduction: namely, the WBC reduction of all cellular blood components transfused in cardiac surgery. Perhaps the best argument for continuing the practice of universal WBC reduction in North America (in regions where it has been implemented) is the —real or perceived— difficulty in identifying, in real time, all the "targeted" patients who will benefit from WBC reduction; whereas the best argument for continuing the practice of universal WBC reduction in Western Europe (in the manner that it is currently employed) is that no case of vCJD has yet been documented in a recipient of a WBC-reduced cellular blood component collected from a donor who later developed vCJD20. Should universal WBC reduction be introduced in regions and/or countries in which it has not yet been implemented? No data from randomised controlled trials have been recently reported that would warrant resurrecting the debate over the appropriateness of introducing universal WBC
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References 1)
Thurer RL, Luban NL, AuBuchon JP, et al. Universal WBC reduction. Transfusion 2000; 40: 751-2. 2) Tsantes AE, Kyriakou E, Nikolopoulos GK, et al. Costeffectiveness of leucoreduction for prevention of febrile, non-haemolytic transfusion reactions. Blood Transfus 2014; 12: 232-7. 3) Vamvakas E, Blajchman MA. Transfusion-related immunomodulation: an update. Blood Rev 2007; 21: 327-48. 4) Jensen LS, Andersen AJ, Christiansen PM, et al. Postoperative infection and natural killer cell function following blood transfusion in patients undergoing elective colorectal surgery. Br J Surg 1992; 79: 513-6. 5) Jensen LS, Kissmeyer-Nielsen P, Wolff B, Quist N. Randomized comparison of leukocyte-depleted versus buffycoat-poor blood transfusion and complications after colorectal surgery. Lancet 1996; 348: 841-5. 6) Tartter PI, Mohandas K, Azar P, et al. Randomized trial comparing packed red cell blood transfusion with and without leukocyte depletion for gastrointestinal surgery. Am J Surg 1998; 176: 462-6. 7) Bilgin YM, van de Watering LMG, Eijsman L, et al. Doubleblind, randomized controlled trial on the effect of leukocytedepleted erythrocyte transfusions in cardiac valve surgery. Circulation 2004; 109: 2755-60. 8) van de Watering LMG, Hermans J, Houbiers JGA, et al. Beneficial effect of leukocyte depletion of transfused blood on post-operative complications in patients undergoing cardiac surgery: a randomized clinical trial. Circulation 1998; 97: 562-8. 9) Nathens AB, Nester TA, Rubenfeld GD, et al. The effects of leukoreduced blood transfusion on infection risk following injury: a randomized controlled trial. Shock 2006; 26: 342-7. 10) Titlestad IL, Ebbesen LS, Ainsworth AP, et al. Leukocytedepletion of blood components does not significantly reduce the risk of infectious complications: results of a double-blind, randomized study. Int J Colorectal Dis 2001; 16: 147-53.
Blood Transfus 2014; 12: 143-5 DOI 10.2450/2014.0009-14 144 All rights reserved - For personal use only No other uses without permission
Universal white blood cell reduction
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21) Strong DM, Shoos Lipton K. Transfusion-related acute lung injury. AABB Association Bulletin #06-07 (November 3, 2006). Bethesda, MD: AABB, 2006. Available at: http:// www.aabb.org/resources/publications/bulletins/Documents/ ab06-07.pdf. Accessed on 04/03/2014. 22) Dodd RY, Shoos Lipton K. Further guidance on methods to detect bacterial contamination of platelet components. AABB Association Bulletin #03-12 (October 1, 2003). Bethesda, MD: AABB, 2003. Available on http://www.aabb.org/resources/ publications/bulletins/Documents/ab03-14.pdf. Accessed on 04/03/2014. 23) Vamvakas EC, Blajchman MA. Blood still kills: six strategies to further reduce allogeneic blood transfusion-related mortality. Transfus Med Rev 2010: 24: 77-124. 24) Vamvakas EC. Can policy decisions in transfusion medicine be evidence-based? In: Vamvakas EC. Decision-Making in Transfusion Medicine. Bethesda, MD: AABB Press, 2011, pp. 1-29.
Correspondence: Eleftherios C. Vamvakas 999 N. Doheny Dr. 1210 Los Angeles, CA 90069, USA e-mail: [email protected]
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11) Wallis JP, Chapman CE, Orr KE, et al. Effect of WBC reduction of transfused RBCs on postoperative infection rates in cardiac surgery. Transfusion 2002; 42: 1127-34. 12) van Hilten JA, van de Watering LMG, van Bockel JH, et al. Effects of transfusion with red cells filtered to remove leukocytes: Randomized controlled trial in patients undergoing major surgery. BMJ 2004; 328: 1281-4. 13) Boshkov LK, Furnary A, Morris C, et al. Prestorage leukoredution of red cells in elective cardiac surgery: results of a double-blind randomized controlled trial. Blood 2004; 104: 112a. 14) Houbiers JGA, Brand A, van de Watering LMG, et al. Randomized controlled trial comparing transfusion of leucocyte-depleted or buffy-coat-depleted blood in surgery for colorectal cancer. Lancet 1994; 344: 573-8. 15) Bracey AW, Radovancevick R, Nussimeier NA, et al. Leukocyte-reduced blood in open-heart surgery patients: effects on outcome. Transfusion 2002; 42 (Suppl): 5S. 16) Dzik WH, Anderson JK, O'Neill EM, et al. A prospective, randomized clinical trial of universal WBC reduction. Transfusion 2002; 42: 1114-22. 17) Nielsen HJ, Hammer J, Kraup AL, et al. Prestorage leukocyte filtration may reduce leukocyte-derived bioactive substance accumulation in patients operated for burn trauma. Burns 1999; 25: 162-70. 18) Vamvakas EC. White-blood-cell containing allogeneic blood transfusion and postoperative infection or mortality: an updated meta-analysis. Vox Sang 2007; 92: 224-32. 19) Bilgin YM, Brand A. Transfusion-related immunomodulation (TRIM): a second hit in an inflammatory cascade? Vox Sang 2008; 95: 261-71. 20) Vamvakas EC. Universal white-blood-cell reduction in Europe: has transmission of vCJD been prevented? Transfus Med Rev 2011; 25: 133-44.
Blood Transfus 2014; 12: 143-5 DOI 10.2450/2014.0009-14 145 All rights reserved - For personal use only No other uses without permission
rv
iz i
Sr l
Notwithstanding the uncertainty about what the USA ICER might be, the study by Tsantes et al.2 raises the question of whether the policy of implementing universal WBC reduction needs to be reconsidered. In 1999, the United Kingdom, Ireland, and Portugal implemented universal WBC reduction of all transfused cellular blood components based on the hypothesis that this intervention might prevent transmission of the agent of variant Creutzfeldt-Jakob disease (vCJD). In North America, there was considerable debate about the appropriateness of introducing universal WBC reduction to prevent the purported adverse effects of allogeneic blood transfusion-related immunomodulation (TRIM)3. In the end, Canada implemented universal WBC reduction but the USA did not, and the proportion of WBC-reduced components transfused by hospitals in the USA today reflects local availability more than clinical preference. More specifically, hospitals in the USA use WBC-reduced components either universally or selectively, depending primarily on their location and the practice of the local blood provider (which may manufacture only leucoreduced or both leucoreduced and non-leucoreduced cellular blood components). Allogeneic blood transfusion results in numerous immunological alterations which may represent mere laboratory curiosities or may reflect some clinically relevant aberration in the recipient's immune function —the so-called "immunomodulatory" effect— of the allogeneic transfusion. The acronym TRIM was initially introduced to designate the constellation of allogeneic blood transfusion-associated laboratory alterations as well as clinical effects (enhanced survival of renal allografts, increased recurrence rate of resected malignancies, increased incidence of post-operative bacterial infections, and activation of endogenous cytomegalovirus and human immunodeficiency virus infection) that could be attributed to allogeneic blood transfusion by immunological mechanisms. More recently, the term has been used more broadly, to encompass additional effects that could be related to allogeneic blood transfusion by means of both immunomodulatory as well as pro-inflammatory mechanisms. Pro-inflammatory, and other poorlyunderstood, effects of allogeneic blood transfusion have been invoked to explain, for example, the association
©
SI M
TI
Se
Proven benefits from white blood cell (WBC) reduction can be secured through selective removal of leucocytes from cellular blood components destined for transfusion to specific categories of patients, that is, patients with a history of febrile, non-haemolytic transfusion reactions (FNHTRs), patients at risk of platelet refractoriness because of receipt of multiple platelet transfusions, and patients at risk of cytomegalovirus disease1. In the absence of considerations of cost, universal leucoreduction of all transfused cellular blood components could extend to all patients these three proven benefits of WBC reduction. Although patients who have not suffered from a FNHTR, are not receiving long-term platelet transfusions, and are not at risk of developing cytomegalovirus disease may derive no immediate benefit from WBC reduction, it is possible that these patients may accrue some tangible benefit in the future. As regards specifically FNHTRs, patients may also accrue some tangible benefit from universal WBC reduction also in the present, because any patient receiving a non-leucoreduced cellular blood component is at risk of developing a FNHTR. It is for this reason that Tsantes et al.2, in this issue of Blood Transfusion, report on the cost-effectiveness of universal WBC reduction for preventing FNHTRs. Among patients transfused with 86,032 units of red blood cells, 0.411% of the recipients of non-WBC-reduced units, compared with 0.047% of the recipients of WBC-reduced units, developed a FNHTR. In Greece, where the study was conducted, the cost of preventing one FNHTR (i.e., the incremental cost-effectiveness ratio [ICER] of € 6,916 or US$ 9,438) was deemed not to be cost-effective by the authors. Nonetheless, the risk of developing FNHTRs was indeed reduced by WBC reduction. Moreover, the calculated ICER and the judgment about whether universal WBC reduction is cost-effective depend, respectively, on the setting in which costs are estimated and the ratio of the calculated ICER to the average cost of a hospitalisation during which a red blood cell transfusion is administered. An ICER of US$ 9,438 might be deemed by some to be cost-effective for the prevention of FNHTRs in at least some US settings, although the cost estimates that resulted in the calculation of this particular ICER in Greece are not directly transferrable to the USA. Blood Transfus 2014; 12: 143-5 DOI 10.2450/2014.0009-14 © SIMTI Servizi Srl
143 All rights reserved - For personal use only No other uses without permission
Vamvakas EC
iz i
Sr l
reduction. Doing so would divert attention from our efforts to reduce other, proven risks of allogeneic blood transfusion. Transfusion-related acute lung injury21, mistransfusion, and bacterial contamination of platelets22 likely remain among the top proven, but not yet fully addressed, risks of blood transfusion23. Since all residual risks of blood transfusion cannot be dealt with simultaneously, policy-makers must carefully select which risk to confront next, so as to accrue the greatest possible societal gain in terms of improved transfusion safety. The greatest "competing risk" when a new safety measure is implemented is what other possible safety improvement(s) is/are left behind, because public resources and attention have been directed to the measure that has been selected for focused debate and/or implementation24. Given the competing risks of TRALI, mistransfusion, and bacterial contamination of platelets, and as also indicated by the cost-effectiveness study of Tsantes et al.2, the most effective way of expending public resources to improve transfusion safety would not be the implementation of universal WBC reduction in regions or countries in which universal WBC reduction has not yet been introduced. The Author declares no conflict of interest.
rv
between allogeneic blood transfusion and increased short-term (up to 3 month post-transfusion) mortality. Twelve randomised controlled trials4-15 comparing subjects randomised to receive non-WBC-reduced vs WBC-reduced allogeneic red blood cells or whole blood and investigating the development of bacterial infection were reported between 1992 and 2005. Eleven randomised controlled trials5,7-13,15-17 reported on shortterm (up to 3-month post-transfusion) mortality from all causes. With regard to bacterial infection, estimates of the TRIM effect have varied from a 7.3-fold increase in the risk of post-operative infection in association with the receipt of non-WBC-reduced (vs WBC-reduced) allogeneic blood transfusion4 to no effect from the transfusion8-15. With the sole exception of the randomised controlled trial by Bilgin et al.7 in the context of cardiac surgery, all randomised controlled trials conducted in the 21st century9-13,15 have consistently produced negative findings. With respect to all-cause, short-term mortality, all studies produced negative findings with the exception of two randomised controlled trials in cardiac surgery8,13. Across all cardiac-surgery studies7,8,11,13,15, there was a 72% increase in mortality in association with nonleucoreduced (compared with leucoreduced) products in the context of allogeneic blood transfusion18. This result conforms with what would have been expected from the immunomodulation theory (that there would be more of a TRIM effect in cardiac surgery, in which the pro-inflammatory effect of the extracorporeal circuit acts as a co-factor, than in other settings19); and it is the only statistically valid and clinically meaningful adverse TRIM effect detected from the 14 available randomised controlled trials4-17. Thus, the comprehensive study of the purported adverse TRIM effects by means of randomised controlled trials added a fourth indication to the three established indications for WBC reduction: namely, the WBC reduction of all cellular blood components transfused in cardiac surgery. Perhaps the best argument for continuing the practice of universal WBC reduction in North America (in regions where it has been implemented) is the —real or perceived— difficulty in identifying, in real time, all the "targeted" patients who will benefit from WBC reduction; whereas the best argument for continuing the practice of universal WBC reduction in Western Europe (in the manner that it is currently employed) is that no case of vCJD has yet been documented in a recipient of a WBC-reduced cellular blood component collected from a donor who later developed vCJD20. Should universal WBC reduction be introduced in regions and/or countries in which it has not yet been implemented? No data from randomised controlled trials have been recently reported that would warrant resurrecting the debate over the appropriateness of introducing universal WBC
©
SI M
TI
Se
References 1)
Thurer RL, Luban NL, AuBuchon JP, et al. Universal WBC reduction. Transfusion 2000; 40: 751-2. 2) Tsantes AE, Kyriakou E, Nikolopoulos GK, et al. Costeffectiveness of leucoreduction for prevention of febrile, non-haemolytic transfusion reactions. Blood Transfus 2014; 12: 232-7. 3) Vamvakas E, Blajchman MA. Transfusion-related immunomodulation: an update. Blood Rev 2007; 21: 327-48. 4) Jensen LS, Andersen AJ, Christiansen PM, et al. Postoperative infection and natural killer cell function following blood transfusion in patients undergoing elective colorectal surgery. Br J Surg 1992; 79: 513-6. 5) Jensen LS, Kissmeyer-Nielsen P, Wolff B, Quist N. Randomized comparison of leukocyte-depleted versus buffycoat-poor blood transfusion and complications after colorectal surgery. Lancet 1996; 348: 841-5. 6) Tartter PI, Mohandas K, Azar P, et al. Randomized trial comparing packed red cell blood transfusion with and without leukocyte depletion for gastrointestinal surgery. Am J Surg 1998; 176: 462-6. 7) Bilgin YM, van de Watering LMG, Eijsman L, et al. Doubleblind, randomized controlled trial on the effect of leukocytedepleted erythrocyte transfusions in cardiac valve surgery. Circulation 2004; 109: 2755-60. 8) van de Watering LMG, Hermans J, Houbiers JGA, et al. Beneficial effect of leukocyte depletion of transfused blood on post-operative complications in patients undergoing cardiac surgery: a randomized clinical trial. Circulation 1998; 97: 562-8. 9) Nathens AB, Nester TA, Rubenfeld GD, et al. The effects of leukoreduced blood transfusion on infection risk following injury: a randomized controlled trial. Shock 2006; 26: 342-7. 10) Titlestad IL, Ebbesen LS, Ainsworth AP, et al. Leukocytedepletion of blood components does not significantly reduce the risk of infectious complications: results of a double-blind, randomized study. Int J Colorectal Dis 2001; 16: 147-53.
Blood Transfus 2014; 12: 143-5 DOI 10.2450/2014.0009-14 144 All rights reserved - For personal use only No other uses without permission
Universal white blood cell reduction
rv
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Sr l
21) Strong DM, Shoos Lipton K. Transfusion-related acute lung injury. AABB Association Bulletin #06-07 (November 3, 2006). Bethesda, MD: AABB, 2006. Available at: http:// www.aabb.org/resources/publications/bulletins/Documents/ ab06-07.pdf. Accessed on 04/03/2014. 22) Dodd RY, Shoos Lipton K. Further guidance on methods to detect bacterial contamination of platelet components. AABB Association Bulletin #03-12 (October 1, 2003). Bethesda, MD: AABB, 2003. Available on http://www.aabb.org/resources/ publications/bulletins/Documents/ab03-14.pdf. Accessed on 04/03/2014. 23) Vamvakas EC, Blajchman MA. Blood still kills: six strategies to further reduce allogeneic blood transfusion-related mortality. Transfus Med Rev 2010: 24: 77-124. 24) Vamvakas EC. Can policy decisions in transfusion medicine be evidence-based? In: Vamvakas EC. Decision-Making in Transfusion Medicine. Bethesda, MD: AABB Press, 2011, pp. 1-29.
Correspondence: Eleftherios C. Vamvakas 999 N. Doheny Dr. 1210 Los Angeles, CA 90069, USA e-mail: [email protected]
©
SI M
TI
Se
11) Wallis JP, Chapman CE, Orr KE, et al. Effect of WBC reduction of transfused RBCs on postoperative infection rates in cardiac surgery. Transfusion 2002; 42: 1127-34. 12) van Hilten JA, van de Watering LMG, van Bockel JH, et al. Effects of transfusion with red cells filtered to remove leukocytes: Randomized controlled trial in patients undergoing major surgery. BMJ 2004; 328: 1281-4. 13) Boshkov LK, Furnary A, Morris C, et al. Prestorage leukoredution of red cells in elective cardiac surgery: results of a double-blind randomized controlled trial. Blood 2004; 104: 112a. 14) Houbiers JGA, Brand A, van de Watering LMG, et al. Randomized controlled trial comparing transfusion of leucocyte-depleted or buffy-coat-depleted blood in surgery for colorectal cancer. Lancet 1994; 344: 573-8. 15) Bracey AW, Radovancevick R, Nussimeier NA, et al. Leukocyte-reduced blood in open-heart surgery patients: effects on outcome. Transfusion 2002; 42 (Suppl): 5S. 16) Dzik WH, Anderson JK, O'Neill EM, et al. A prospective, randomized clinical trial of universal WBC reduction. Transfusion 2002; 42: 1114-22. 17) Nielsen HJ, Hammer J, Kraup AL, et al. Prestorage leukocyte filtration may reduce leukocyte-derived bioactive substance accumulation in patients operated for burn trauma. Burns 1999; 25: 162-70. 18) Vamvakas EC. White-blood-cell containing allogeneic blood transfusion and postoperative infection or mortality: an updated meta-analysis. Vox Sang 2007; 92: 224-32. 19) Bilgin YM, Brand A. Transfusion-related immunomodulation (TRIM): a second hit in an inflammatory cascade? Vox Sang 2008; 95: 261-71. 20) Vamvakas EC. Universal white-blood-cell reduction in Europe: has transmission of vCJD been prevented? Transfus Med Rev 2011; 25: 133-44.
Blood Transfus 2014; 12: 143-5 DOI 10.2450/2014.0009-14 145 All rights reserved - For personal use only No other uses without permission
