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Leucorreducción para la prevención de las reacciones adversas de la transfusión de sangre alogénica

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References

Referencias de los estudios incluidos en esta revisión

Bilgin 2004 {published data only}

Bilgin YM, Van De Watering LM, Eijsman L, Versteegh MI, Brand R, Van Oers MH, et al. Double‐blind, randomized controlled trial on the effect of leukocyte‐depleted erythrocyte transfusions in cardiac valve surgery. Circulation 2004;109(22):2755‐60. [PUBMED: 15148271]

Boshkov 2006 {published data only}

Boshkov LK, Chien G, VanWinkle D, Furnary AP, Wu Y, Grunkemeirer GI, et al. Prestorage leukoreduction of transfused packed red cells is associated with significant ongoing 1‐12 month survival benefit cardiac surgery patients. Blood 2006;108:578.

Collier 2001 {published data only}

Collier AC, Kalish LA, Busch MP, Gernsheimer T, Assmann SF, Lane TA, et al. Leukocyte‐reduced red blood cell transfusions in patients with anemia and human immunodeficiency virus infection: the Viral Activation Transfusion Study: a randomized controlled trial. JAMA 2001;285(12):1592‐601. [PUBMED: 11268267]
Lane TA, Gernsheimer T, Mohandas K, Assmann SF. Signs and symptoms associated with the transfusion of WBC‐reduced RBCs and non‐WBC‐reduced RBCs in patients with anemia and HIV infection: results from the Viral Activation Transfusion Study. Transfusion 2002;42(2):265‐74. [PUBMED: 11896345]

Donati 2014 {published data only}

Donati A, Damiani E, Luchetti M, Domizi R, Scorcella C, Carsetti A, et al. Microcirculatory effects of the transfusion of leukodepleted or non‐leukodepleted red blood cells in patients with sepsis: a pilot study. Critical Care 2014;18(1):R33. [PUBMED: 24528648]

Jensen 1996 {published data only}

Jensen LS, Kissmeyer‐Nielsen P, Wolff B, Qvist N. Randomised comparison of leucocyte‐depleted versus buffy‐coat‐poor blood transfusion and complications after colorectal surgery. Lancet 1996;348(9031):841‐5. [PUBMED: 8826808]

Lapierre 2007 {published data only}

Lapierre V, Aupérin A, Robinet E, Ferrand C, Oubouzar N, Tramalloni D, et al. Immune modulation and microchimerism after unmodified versus leukoreduced allogeneic red blood cell transfusion in cancer patients: results of a randomized study. Transfusion 2007;47(9):1691‐9. [PUBMED: 17725736]

Nathens 2006 {published data only}

Nathens AB, Nester TA, Rubenfeld GD, Nirula R, Gernsheimer TB. The effects of leukoreduced blood transfusion on infection risk following injury: a randomized controlled trial. Shock 2006;26(4):342‐7. [PUBMED: 16980879]
Watkins TR, Rubenfeld GD, Martin TR, Nester TA, Caldwell E, Billgren J, et al. Effects of leukoreduced blood on acute lung injury after trauma: a randomized controlled trial. Critical Care Medicine 2008;36(5):1493‐9. [PUBMED: 18434890]

Sanfilippo 1985 {published data only}

Sanfilippo FP, Bollinger RR, MacQueen JM, Brooks BJ, Koepke JA. A randomized study comparing leukocyte‐depleted versus packed red cell transfusions in prospective cadaver renal allograft recipients. Transfusion 1985;25(2):116‐9. [PUBMED: 3885483]

Tartter 1998 {published data only}

Tartter PI, Mohandas K, Azar P, Endres J, Kaplan J, Spivack M. Randomized trial comparing packed red cell blood transfusion with and without leukocyte depletion for gastrointestinal surgery. American Journal of Surgery 1998;176(5):462‐6. [PUBMED: 9874434]

Titlestad 2001 {published data only}

Titlestad IL, Ebbesen LS, Ainsworth AP, Lillevang ST, Qvist N, Georgsen J. Leukocyte‐depletion of blood components does not significantly reduce the risk of infectious complications. Results of a double‐blinded, randomized study. International Journal of Colorectal Disease 2001;16(3):147‐53. [PUBMED: 11459288]

van de Watering 1998 {published data only}

van de Watering LM, Hermans J, Houbiers JG, van den Broek PJ, Bouter H, Boer F, 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(6):562‐8. [PUBMED: 9494026]

van Hilten 2004 {published data only}

Lange MM, van Hilten JA, van de Watering LM, Bijnen BA, Roumen RM, Putter H, et al. Leucocyte depletion of perioperative blood transfusion does not affect long‐term survival and recurrence in patients with gastrointestinal cancer. The British Journal of Surgery 2009;96(7):734‐40. [PUBMED: 19526613]
van Hilten JA, van de Watering LM, van Bockel JH, van de Velde CJ, Kievit J, Brand R, et al. Effects of transfusion with red cells filtered to remove leucocytes: randomised controlled trial in patients undergoing major surgery. BMJ 2004;328(7451):1281. [PUBMED: 15142885]

Wallis 2002 {published data only}

Wallis JP, Chapman CE, Orr KE, Clark SC, Forty JR. Effect of WBC reduction of transfused RBCs on postoperative infection rates in cardiac surgery. Transfusion 2002;42(9):1127‐34. [PUBMED: 12430668]

Referencias de los estudios excluidos de esta revisión

Bowden 1995 {published data only}

Bowden RA, Slichter SJ, Sayers M, Weisdorf D, Cays M, Schoch G, et al. A comparison of filtered leukocyte‐reduced and cytomegalovirus (CMV) seronegative blood products for the prevention of transfusion‐associated CMV infection after marrow transplant. Blood 1995;86(9):3598‐603. [PUBMED: 7579469]

Bracey 2002 {published data only}

Bracey AW, Radovancevic R, Nussmeier NA. Leukocyte‐depleted blood in open‐heart surgery patients: effects on outcome. Transfusion 2002;42(Suppl):5S.

Connery 2005 {published data only}

Connery CP, Toumpoulis IK, Anagnostopoulos CE, Hillel Z, Rahman FG, Katritsis D, et al. Does leukofiltration reduce pulmonary infections in CABG patients? A prospective, randomized study with early results and mid‐term survival. Acta Cardiologica 2005;60(3):285‐93. [PUBMED: 15999468]

de Vries 2003 {published data only}

de Vries AJ, Gu YJ, Post WJ, Vos P, Stokroos I, Lip H, et al. Leucocyte depletion during cardiac surgery: a comparison of different filtration strategies. Perfusion 2003;18(1):31‐8. [PUBMED: 12705648]

de Vries 2004 {published data only}

de Vries AJ, Gu YJ, van Oeveren W. Leucocyte filtration of residual heart‐lung machine blood in children undergoing congenital heart surgery. Perfusion 2004;19(6):345‐9. [PUBMED: 15619967]

Dzik 2002 {published data only}

Dzik WH, Anderson JK, O'Neill EM, Assmann SF, Kalish LA, Stowell CP. A prospective, randomized clinical trial of universal WBC reduction. Transfusion 2002;42(9):1114‐22. [PUBMED: 12430666]

Efstathiou 2003 {published data only}

Efstathiou A, Vlachveis M, Tsonis G, Asteri T, Psarakis A, Fessatidis IT. Does leukodepletion during elective cardiac surgery really influence the overall clinical outcome?. The Journal of Cardiovascular Surgery 2003;44(2):197‐204. [PUBMED: 12813383]

Gilbert 1989 {published data only}

Gilbert GL, Hayes K, Hudson IL, James J. Prevention of transfusion‐acquired cytomegalovirus infection in infants by blood filtration to remove leucocytes. Neonatal Cytomegalovirus Infection Study Group. Lancet (London, England) 1989;1(8649):1228‐31. [PUBMED: 2566781]

Gu 1996 {published data only}

Gu YJ, de Vries AJ, Boonstra PW, van Oeveren W. Leukocyte depletion results in improved lung function and reduced inflammatory response after cardiac surgery. The Journal of Thoracic and Cardiovascular Surgery 1996;112(2):494‐500. [PUBMED: 8751518]

Gu 2009 {published data only}

Gu YJ, de Vries AJ, Hagenaars JA, van Oeveren W. Leucocyte filtration of salvaged blood during cardiac surgery: effect on red blood cell function in concentrated blood compared with diluted blood. European Journal of Cardio‐Thoracic Surgery 2009;36(5):877‐82. [PUBMED: 19608429]

Hayashi 2000 {published data only}

Hayashi Y, Sawa Y, Nishimura M, Ichikawa H, Kagisaki K, Ohtake S, et al. Clinical evaluation of leukocyte‐depleted blood cardioplegia for pediatric open heart operation. The Annals of Thoracic Surgery 2000;69(6):1914‐9. [PUBMED: 10892946]

Houbiers 1994 {published data only}

Houbiers JG, Brand A, Van De Watering LM, Hermans J, Verwey PJ, Bijnen AB, et al. Randomised controlled trial comparing transfusion of leucocyte‐depleted or buffy‐coat‐depleted blood in surgery for colorectal cancer. Lancet 1994;344(8922):573‐8. [PUBMED: 7914960]
Van De Watering LM, Brand A, Houbiers JG, Klein Kranenbarg WM, Hermans J, Van De Velde C. Perioperative blood transfusions, with or without allogeneic leucocytes, relate to survival, not to cancer recurrence. The British Journal of Surgery 2001;88(2):267‐72. [PUBMED: 11167879]

Jensen 1992 {published data only}

Jensen LS, Andersen AJ, Christiansen PM, Hokland P, Juhl CO, Madsen G, et al. Postoperative infection and natural killer cell function following blood transfusion in patients undergoing elective colorectal surgery. The British Journal of Surgery 1992;79(6):513‐6. [PUBMED: 1611441]
Jensen LS, Hokland M, Nielsen HJ. A randomized controlled study of the effect of bedside leucocyte depletion on the immunosuppressive effect of whole blood transfusion in patients undergoing elective colorectal surgery. The British Journal of Surgery 1996;83(7):973‐7. [PUBMED: 8813790]

Kao 1995 {published data only}

Kao KJ, Mickel M, Braine HG, Davis K, Enright H, Gernsheimer T, et al. White cell reduction in platelet concentrates and packed red cells by filtration: a multicenter clinical trial. The Trap Study Group. Transfusion 1995;35(1):13‐9. [PUBMED: 7998062]

Koskenkari 2005 {published data only}

Koskenkari J, Rimpiläinen J, Biancari F, Surcel HM, Kaukoranta P, Kiviluoma K, et al. Leukocyte depleting filter attenuates myocardial injury during elective coronary artery bypass surgery. Scandinavian Cardiovascular Journal 2005;39(6):358‐68. [PUBMED: 16352489]

Leal‐Noval 2005 {published data only}

Leal‐Noval SR, Amaya R, Herruzo A, Hernández A, Ordóñez A, Marín‐Niebla A, et al. Effects of a leukocyte depleting arterial line filter on perioperative morbidity in patients undergoing cardiac surgery: a controlled randomized trial. The Annals of Thoracic Surgery 2005;80(4):1394‐400. [PUBMED: 16181877]

Llewelyn 2004 {published data only}

Llewelyn CA, Taylor RS, Todd AA, Stevens W, Murphy MF, Williamson LM. The effect of universal leukoreduction on postoperative infections and length of hospital stay in elective orthopedic and cardiac surgery. Transfusion 2004;44(4):489‐500. [PUBMED: 15043563]

Nielsen 1999 {published data only}

Nielsen HJ, Hammer JH, Krarup AL, Nielsen LM, Reimert CM, Pedersen AN, et al. Prestorage leukocyte filtration may reduce leukocyte‐derived bioactive substance accumulation in patients operated for burn trauma. Burns 1999;25(2):162‐70. [PUBMED: 10208393]

Opelz 1997 {published data only}

Opelz G, Vanrenterghem Y, Kirste G, Gray DW, Horsburgh T, Lachance JG, et al. Prospective evaluation of pretransplant blood transfusions in cadaver kidney recipients. Transplantation 1997;63(7):964‐7. [PUBMED: 9112348]

Salamonsen 2005 {published data only}

Salamonsen RF, Anderson J, Anderson M, Bailey M, Magrin G, Rosenfeldt F. Total leukocyte control for elective coronary bypass surgery does not improve short‐term outcome. The Annals of Thoracic Surgery 2005;79(6):2032‐8. [PUBMED: 15919304]

Skånberg 2007 {published data only}

Skånberg J, Lundholm K, Haglind E. Effects of blood transfusion with leucocyte depletion on length of hospital stay, respiratory assistance and survival after curative surgery for colorectal cancer. Acta Oncologica 2007;46(8):1123‐30. [PUBMED: 17851860]

So‐Osman 2010 {published data only}

So‐Osman C, Nelissen R, Te Slaa R, Coene L, Brand R, Brand A. A randomized comparison of transfusion triggers in elective orthopaedic surgery using leucocyte‐depleted red blood cells. Vox Sanguinis 2010;98(1):56‐64. [PUBMED: 19656349]

Vamvakas 2007 {published data only}

Vamvakas EC. White‐blood‐cell‐containing allogeneic blood transfusion and postoperative infection or mortality: an updated meta‐analysis. Vox Sanguinis 2007;92(3):224‐32. [PUBMED: 17348871]

van de Watering 2004 {published data only}

van de Watering L. What has universal leucodepletion given us: evidence from clinical trials?. Vox Sanguinis 2004;87 Suppl 2:139‐42. [PUBMED: 15209899]

Referencias de los estudios en espera de evaluación

NCT00810810 {published data only}

Immunomodulation Following Transfusion. https://clinicaltrials.gov/ct2/show/NCT00810810.

Waghmare 2012 {published data only}

Waghmare N, Desai N, Karnad D. Open Labeled, Randomized, Controlled Trial Comparing Leukodepleted (Filtered) Blood Transfusion and Non‐Leukodepleted (Unfiltered) Blood Transfusion in Cases of Severe Falciparum Malaria. Chest. Glenview (IL): Proceedings of the CHEST 2012 Annual Meeting, Atlanta (GA), October 2012; Vol. 142:Meeting Abstracts: 232A.

Zhao 2004 {published data only}

Zhao S, Chen X, Hu J, Li R. Clinical assessment of preventing febrile nonhemolytic transfusion reaction by leukocyte‐depleted blood transfusion. Zhongguo Shi Yan Xue Ye Xue Za Zhi [Journal of Experimental Hematology] 2002;10(6):568‐70. [PUBMED: 12513724 ]

AETSA 2007

Aguado M, Villegas R, Márquez S, Corbacho B, Navarro J. Universal leukorreduction. A systematic review of the literature and an economic assessment. Executive summary [Leucorreducción universal de productos sanguíneos. Revisión Sistemática de la Literatura y Evaluación Económica.]. Agencia de Evaluación de Tecnologías Sanitarias de Andalucía2007:1‐95.

Balshem 2011

Balshem H, Helfand M, Schünemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. Journal of Clinical Epidemiology 2011;64(4):401‐6. [PUBMED: 21208779]

Blajchman 2002

Blajchman MA. Immunomodulation and blood transfusion. American Journal of Therapeutics 2002;9(5):389‐95. [PUBMED: 12237730]

Blajchman 2004

Blajchman MA, Goldman M, Webert KE, Vamvakas EC, Hannon J, Delage G. Proceedings of a consensus conference: the screening of blood donors for variant CJD. Transfusion Medicine Reviews 2004;18(2):73‐92. [PUBMED: 15067588]

Blajchman 2006

Blajchman MA. The clinical benefits of the leukoreduction of blood products. The Journal of Trauma 2006;60(6 Suppl):S83‐90. [PUBMED: 16763486]

Blajchman 2010

Blajchman MA, Glynn SA, Josephson CD, Kleinman SH, State‐of‐the Science Symposium Transfusion Medicine Committee. Clinical trial opportunities in Transfusion Medicine: proceedings of a National Heart, Lung, and Blood Institute State‐of‐the‐Science Symposium. Transfusion Medicine Reviews 2010;24(4):259‐85. [PUBMED: 20851330]

Blumberg 1998

Blumberg N. Perioperative allogeneic blood transfusion does not cause adverse sequelae in patients with cancer: a meta‐analysis of unconfounded studies. The British Journal of Surgery 1998;85(8):1163‐4. [PUBMED: 9718033]

Blumberg 2007

Blumberg N, Zhao H, Wang H, Messing S, Heal JM, Lyman GH. The intention‐to‐treat principle in clinical trials and meta‐analyses of leukoreduced blood transfusions in surgical patients. Transfusion 2007;47(4):573‐81. [PUBMED: 17381614]

Blumberg 2010

Blumberg N, Heal JM, Gettings KF, Phipps RP, Masel D, Refaai MA, et al. An association between decreased cardiopulmonary complications (transfusion‐related acute lung injury and transfusion‐associated circulatory overload) and implementation of universal leukoreduction of blood transfusions. Transfusion 2010;50(12):2738‐44. [PUBMED: 20561296]

Brozek 2011

Brozek JL, Akl EA, Compalati E, Kreis J, Terracciano L, Fiocchi A, et al. Grading quality of evidence and strength of recommendations in clinical practice guidelines part 3 of 3. The GRADE approach to developing recommendations. Allergy 2011;66(5):588‐95. [PUBMED: 21241318]

Carson 2012

Carson JL, Carless PA, Hebert PC. Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion. Cochrane Database of Systematic Reviews 2012, Issue 4. [DOI: 10.1002/14651858.CD002042.pub3; PUBMED: 22513904]

CCOHTA 1998

Gibis B, Baladi JF. Leukoreduction: the techniques used, their effectiveness and costs. Canadian Coordinating Office for Health Technology Assessmnet (CCOHTA). https://www.cadth.ca/sites/default/files/pdf/leukoreduct_tr_e.pdf (accessed 15 August 2015). [IBSN 1‐895561‐60‐4]

Chan 2013

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Dellinger 2004

Dellinger EP, Anaya DA. Infectious and immunologic consequences of blood transfusion. Critical Care 2004;8(Suppl 2):S18‐23. [PUBMED: 15196317]

Dwyre 2008

Dwyre DM, Holland PV. Transfusion‐associated graft‐versus‐host disease. Vox Sanguinis 2008;95(2):85‐93. [PUBMED: 18544121]

Fergusson 2004

Fergusson D, Khanna MP, Tinmouth A, Hébert PC. Transfusion of leukoreduced red blood cells may decrease postoperative infections: two meta‐analyses of randomized controlled trials. Canadian Journal of Anaesthesia (Journal Canadien d'Anesthésie) 2004;51(5):417‐24. [PUBMED: 15128625]

Flohé 2007

Flohé S, Kobbe P, Nast‐Kolb D. Immunological reactions secondary to blood transfusion. Injury 2007;38(12):1405‐8. [PUBMED: 18048035]

Friese 2008

Friese RS, Sperry JL, Phelan HA, Gentilello LM. The use of leukoreduced red blood cell products is associated with fewer infectious complications in trauma patients. American Journal of Surgery 2008;196(1):56‐61. [PUBMED: 18513694]

Gabriel 2012

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Galel 2009

Galel SA, Nguyen DD, Fontaine MJ, Goodnough LT, Viele MK. Transfusion Medicine. In: Greer JP, Foerster J, Rodgers GM, Paraskevas F, Glader B, Arber DA editor(s). Wintrobe's Clinical Hematology. 12th Edition. Vol. 1, Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2009:672‐721.

Goldman 2005

Goldman M, Webert KE, Arnold DM, Freedman J, Hannon J, Blajchman MA. Proceedings of a consensus conference: towards an understanding of TRALI. Transfusion Medicine Reviews 2005;19(1):2‐31. [PUBMED: 15830325]

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Guyatt 2011b

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Guyatt 2011d

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Heddle 1999

Heddle NM. Pathophysiology of febrile nonhemolytic transfusion reactions. Current Opinion in Hematology 1999;6(6):420‐6. [PUBMED: 10546797]

Hendrickson 2009

Hendrickson JE, Hillyer CD. Noninfectious serious hazards of transfusion. Anesthesia and Analgesia 2009;108(3):759‐69. [PUBMED: 19224780]

Hiesse 2001

Hiesse C, Busson M, Buisson C, Farahmand H, Bierling P, Benbunan M, et al. Multicenter trial of one HLA‐DR‐matched or mismatched blood transfusion prior to cadaveric renal transplantation. Kidney International 2001;60(1):341‐9. [PUBMED: 11422770]

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Jensen 1998

Jensen LS. Benefits of leukocyte‐reduced blood transfusions in surgical patients. Current Opinion in Hematology 1998;5(6):376‐80. [PUBMED: 9814642]

King 2004

King KE, Shirey RS, Thoman SK, Bensen‐Kennedy D, Tanz WS, Ness PM. Universal leukoreduction decreases the incidence of febrile nonhemolytic transfusion reactions to RBCs. Transfusion 2004;44(1):25‐9. [PUBMED: 14692963]

Laupacis 2001

Laupacis A, Brown J, Costello B, Delage G, Freedman J, Hume H, et al. Prevention of posttransfusion CMV in the era of universal WBC reduction: a consensus statement. Transfusion 2001;41(4):560‐9. [PUBMED: 11316911]

Lavoie 2011

Lavoie J. Blood transfusion risks and alternative strategies in pediatric patients. Paediatric Anaesthesia 2011;21(1):14‐24. [PUBMED: 21155923]

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Lindholm 2011

Lindholm PF, Annen K, Ramsey G. Approaches to minimize infection risk in blood banking and transfusion practice. Infectious Disorders Drug Targets 2011;11(1):45‐56. [PUBMED: 21303341]

Looney 2006

Looney MR, Su X, Van Ziffle JA, Lowell CA, Matthay MA. Neutrophils and their Fc gamma receptors are essential in a mouse model of transfusion‐related acute lung injury. The Journal of Clinical Investigation 2006;116(6):1615‐23. [PUBMED: 16710475]

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Mukagatare 2010

Mukagatare I, Monfort M, de Marchin J, Gerard C. The effect of leukocyte‐reduction on the transfusion reactions to red blood cells concentrates [Effet de la déleucocytation des concentrés érythrocytaires sur les réactions transfusionnelles]. Transfusion Clinique et Biologique 2010;17(1):14‐9. [PUBMED: 20106700]

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Phelan 2007

Phelan HA, Sperry JL, Friese RS. Leukoreduction before red blood cell transfusion has no impact on mortality in trauma patients. Journal of Surgical Research 2007;138(1):32‐6. [PUBMED: 17161430]

Renaudier 2009

Renaudier P, Rebibo D, Waller C, Schlanger S, Vo Mai MP, Ounnoughene N, et al. Pulmonary complications of transfusion (TACO‐TRALI) [Complications pulmonaires de la transfusion (TACO–TRALI)]. Transfusion Clinique et Biologique 2009;16(2):218‐32. [PUBMED: 19446484]

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Rohde JM, Dimcheff DE, Blumberg N, Saint S, Langa KM, Kuhn L, et al. Health care‐associated infection after red blood cell transfusion: a systematic review and meta‐analysis. JAMA 2014;311(13):1317‐26. [PUBMED: 24691607]

Rühl 2009

Rühl H, Bein G, Sachs UJ. Transfusion‐associated graft‐versus‐host disease. Transfusion Medicine Reviews 2009;23(1):62‐71. [PUBMED: 19056035]

Sachs 2010

Sachs UJ. Non‐infectious serious hazards in plasma transfusion. Transfusion and Apheresis Science 2010;43(3):381‐6. [PUBMED: 20934385]

Sachs 2011

Sachs UJ, Wasel W, Bayat B, Bohle RM, Hattar K, Berghöfer H, et al. Mechanism of transfusion‐related acute lung injury induced by HLA class II antibodies. Blood 2011;117(2):669‐77. [PUBMED: 21030555]

Schulz 2010

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Shapiro MJ. To filter blood or universal leukoreduction: what is the answer?. Critical Care 2004;8 Suppl 2:S27‐30. [PUBMED: 15196319]

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Tenorio 2007

Tenorio GC, Gupte SC, Munker R. Transfusion Medicine and Immunohematology. In: Munker R, Hiller E, Glass J,  Paquette R editor(s). Modern Hematology. 2nd Edition. Totowa, NJ: Humana Press Inc, 2007:401‐32. [ISBN‐13: 978‐1‐58829‐557‐6]

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Theusinger OM, Spahn DR, Ganter MT. Transfusion in trauma: why and how should we change our current practice?. Current Opinion in Anaesthesiology 2009;22(2):305‐12. [PUBMED: 19390257]

Thorlund 2011 [Computer program]

Thorlund K, Engstrøm J, Wetterslev J, Brok J, Imberger G, Gluud C. User manual for trial sequential analysis (TSA). Version available from www.ctu.dk/tsa. Copenhagen, Denmark: Copenhagen Trial Unit: Centre for Clinical Intervention Research, 2011.

Tien 2007

Tien H, Nascimento B, Callum J, Rizoli S. An approach to transfusion and hemorrhage in trauma: current perspectives on restrictive transfusion strategies. Canadian Journal of Surgery 2007;50(3):202‐9. [PUBMED: 17568492]

Tobian 2011

Tobian AA, Savage WJ, Tisch DJ, Thoman S, King KE, Ness PM. Prevention of allergic transfusion reactions to platelets and red blood cells through plasma reduction. Transfusion 2011;51(8):1676‐83. [PUBMED: 21214585]

Toy 2005

Toy P, Popovsky MA, Abraham E, Ambruso DR, Holness LG, Kopko PM, et al. Transfusion‐related acute lung injury: definition and review. Critical Care Medicine 2005;33(4):721‐6. [PUBMED: 15818095]

Triulzi 2009

Triulzi DJ. Transfusion‐related acute lung injury: current concepts for the clinician. Anesthesia and Analgesia 2009;108(3):770‐6. [PUBMED: 19224781]

Tsai 2010

Tsai AG, Hofmann A, Cabrales P, Intaglietta M. Perfusion vs. oxygen delivery in transfusion with "fresh" and "old" red blood cells: the experimental evidence. Transfusion and Apheresis Science 2010;43(1):69‐78. [PUBMED: 20646963]

Tsantes 2014

Tsantes AE, Kyriakou E, Nikolopoulos GK, Stylos D, Sidhom M, Bonovas S, et al. Cost‐effectiveness of leucoreduction for prevention of febrile non‐haemolytic transfusion reactions. Blood Transfusion 2014;12(2):232‐7. [PUBMED: 24931843]

Vamvakas 1996

Vamvakas EC, Carven JH, Hibberd PL. Blood transfusion and infection after colorectal cancer surgery. Transfusion 1996;36(11‐12):1000‐8. [PUBMED: 8937412]

Vamvakas 2001

Vamvakas EC, Blajchman MA. Deleterious clinical effects of transfusion‐associated immunomodulation: fact or fiction?. Blood 2001;97(5):1180‐95. [PUBMED: 11222359]

Vamvakas 2006

Vamvakas EC. Deleterious clinical effects of allogenic blood tranfusion‐related immunomodulation. Facts or fiction? An update through 2005. American Journal of Clinical Pathology 2006;126(Suppl 1):S71‐85. [DOI: 10.1309/9B7RWAYVVLCL58WW]

Vamvakas 2009

Vamvakas EC, Blajchman MA. Transfusion‐related mortality: the ongoing risks of allogeneic blood transfusion and the available strategies for their prevention. Blood 2009;113(15):3406‐17. [PUBMED: 19188662 ]

Wagner 2004

Wagner SJ. Transfusion‐transmitted bacterial infection: risks, sources and interventions. Vox Sanguinis 2004;86(3):157‐63. [PUBMED: 15078249]

Watkins 2008

Watkins TR, Rubenfeld GD, Martin TR, Nester TA, Caldwell E, Billgren J, et al. Effects of leukoreduced blood on acute lung injury after trauma: a randomized controlled trial. Critical Care Medicine 2008;36(5):1493‐9. [PUBMED: 18434890]

Wetterslev 2008

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Referencias de otras versiones publicadas de esta revisión

Simancas‐Racines 2012

Simancas‐Racines D, Martí‐Carvajal AJ, Hidalgo R, Bangdiwala S. Leukoreduction for the prevention of adverse reactions from allogeneic blood transfusion. Cochrane Database of Systematic Reviews 2012, Issue 3. [DOI: 10.1002/14651858.CD009745]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Bilgin 2004

Methods

Design: Parallel group RCT

Country: The Netherlands

Multicentre study: Yes (two university hospitals: Academic Medical Center and Leiden University Medical Center)

Setting: Hospital

Follow‐up: 90 days

Unit of allocation: Patients

Unit of analysis: Patients

Participants

Inclusion criteria: Adults > 18 years undergoing valve surgery

Exclusion criteria: Those with a medical indication for leukocyte‐depleted erythrocytes or who had received blood transfusions within the previous three months

Patients enrolled: 496

Patients randomised: 474

Buffy coat‐depleted packed cells: 237

Leukocyte‐depleted erythrocytes (LDs): 237

Patients transfused: not clearly reported

Patients considered for the analysis: 474

Main characteristics of patients:

Age: Buffy coat‐depleted packed cells group = 66.6 ± 12.5 years; LD group = 65.3 ± 14.7 years

Percentage of men: Buffy coat‐depleted packed cells group = 57%; LD group = 52%

Percentage of erythrocyte transfusions more or equal to four: Buffy coat‐depleted packed cells group= 55.3%; LD group= 61.2%

Storage time of the units: Buffy coat‐depleted packed cells group = 19.7 ± 5.4 ; LD group = 17.4 ± 5

Percentage of use of aprotinin: Buffy coat‐depleted packed cells group = 37.1; LD group = 36.3

Interventions

  1. Experimental: Leukocyte‐depleted erythrocytes (LDs) (pre‐storage leukoreduction).

  2. Control: Buffy coat–depleted packed cells (PCs).

Co‐intervention:

  1. Quote: "Not all patients underwent induced hypothermia (29° to 33°C). In one hospital, aprotinin was used in some patients; this hospital had a medium‐care ward. Prophylactic antibiotics were given to all patients for 48 hours." (Page 2756).

  2. Quote: "Platelet concentrates were prepared from pooled buffy coats and were all leukocyte‐depleted by filtration (< 1 x 106 leukocytes per product) before storage".

Outcomes

Primary:

  1. Mortality at 90 days after surgery.

Secondary:

  1. Incidence of in‐hospital mortality.

  2. Causes of death.

  3. Incidence of multiple organ dysfunction syndrome.

  4. Infections during the hospital stay.

  5. Duration of ICU stay.

  6. Hospitalization.

Quote: "An independent safety committee monitored the interim results of the primary end point." (Page 2757).

Notes

Trial registration: Not reported

Funding: This study was financially supported by the Netherlands Heart Foundation (grant 98.183) (Page 2760)

Rol of sponsor: Not reported

A priori sample size estimation: Yes

Conducted: Between June 1999 and May 2001

Declared conflicts of interest: Not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "a straightforward randomizations was performed by using a fixed block size (n=24) to ensure a balance between the randomizations groups" (Page 2756).

Allocation concealment (selection bias)

Low risk

Quote: "...the technicians randomly assigned the patients by opening a sealed and numbered envelope." "In the hospital electronic information system, a code was used during the study period to hide the random assignment" (Page 2756).

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "The patients, surgeons, anaesthesiologists, and the trial coordinators were blinded to the random assignment, as the technicians placed uniform study labels on the description on the erythrocyte bags" (Page 2756).

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: "The patients, surgeons, anesthesiologists, and the trial coordinators were blinded to the random assignment, as the technicians placed uniform study labels on the description on the erythrocyte bags. In the hospital electronic information system, a code was used during the study period to hide the random assignment" (Page 2756).

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Loss after transfusion: 0.4% (2/474)

Loss after transfusion in prestorage by filtration of LDs (LDs): 0.8% (2/237)

Loss after transfusion in Buffy coat–depleted packed cells (PCs): 0% (0/237)

Loss after transfusion. Imbalance between comparison groups: 0.8%

Selective reporting (reporting bias)

Low risk

Comment: The study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre‐specified (convincing text of this nature may be uncommon).

Other bias

Low risk

The study appears to be free of other sources of bias.

Boshkov 2006

Methods

Design: Parallel group RCT

Country: USA

Multicentre study: Yes (three centre trial)

Setting: Hospital

Follow‐up: 2 to 12 months

Unit of allocation: Patients

Unit of analysis: Patients

Participants

Inclusion criteria:

  • Undergoing coronary artery bypass grafting, cardiac valve replacement or a combination of the two.

Exclusion criteria: Not reported in the abstract

  • Patients enrolled: Not clearly reported in the abstract.

  • Patients randomised: 1226.

Prestorage leukoreduced RBC (LR‐RBCs): The number of patients is not clearly reported in the abstract.

Standard RBCs (S‐RBCs): The number of patients is not clearly reported in the abstract.

  • Patients transfused: 562.

  • Patients considered for the analysis: Not clearly reported in the abstract.

Main characteristics of patients:

"Groups were statistically equivalent demographically and by all Society of Thoracic Surgery risk criteria".

Interventions

  1. Experimental: LR‐RBCs (pre‐storage leukoreduction).

  2. Control: S‐RBCs.

Co‐intervention: not reported in the abstract

Outcomes

Primary:

  1. Operative and postoperative mortality at 60 days after surgery.

Secondary: Not reported in the abstract.

Notes

Trial registration: Not reported in the abstract

Funding: Not reported in the abstract

Role of sponsor: Not reported in the abstract

A priori sample size estimation: Not reported in the abstract

Conducted: Not reported in the abstract

Declared conflicts of interest: "No relevant conflicts of interest to declare" (reported in the abstract)

Other relevant information: All study characteristics were obtained from the abstract. We tried to contact two trial authors by email, but no response has not yet been obtained

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "patients (undergoing coronary artery bypass grafting, cardiac valve replacement, or a combination of the two) were pre‐operatively randomised to receive either LR‐ or S‐RBCs (Abstract).

Insufficient information to permit judgement of ‘low risk’ or ‘high risk’.

Allocation concealment (selection bias)

Unclear risk

Comment: Insufficient information to permit judgement of ‘low risk’ or ‘high risk’.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote: "Patients and clinicians were blinded as to product type" (Abstract).

The blinding methods are not clearly reported.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: "Patients and clinicians were blinded as to product type" (Abstract).

Comments: No blinding or incomplete blinding, but the review authors judge that the outcome is not likely to be influenced by lack of blinding.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

"562 patients (45.8%) were transfused: 304 received LR‐RBCs and 258 S‐RBCs" (Abstract)

Loss after transfusion: Not reported in the abstract

Loss after transfusion LR group: Not reported in the abstract

Loss after transfusion Control group: Not reported in the abstract

Loss after transfusion. Imbalance between comparison groups: Not reported in the abstract.

Comment: Insufficient reporting of attrition/exclusions to permit judgement of ‘low risk’ or ‘high risk’ (e.g. number randomised not stated, no reasons for missing data provided).

Selective reporting (reporting bias)

Unclear risk

Comment: Insufficient information to permit judgement of ‘low risk’ or ‘high risk’ (Abstract data).

Other bias

High risk

Design bias: 1226 patients randomised; only 562 (45.8) were transfused.

Collier 2001

Methods

Design: Parallel group RCT

Country: USA

Multicentre study: Yes (11 academic medical centres)

Setting: Hospital

Follow‐up: 12 months

Unit of allocation: Patients

Unit of analysis: Patients

Participants

Inclusion criteria:

Those 14 years of older, with confirmed HIV infection and documented CMV infection (by chart or antibody testing), Karnofsky performance score of ≥ 40, expected survival of more than 1 month, symptomatic anaemia requiring red blood concentrates transfusion and no received transfusions within 72 hours of enrolment.

Exclusion criteria:

Those with a surgical reason for transfusion, a priori history for transfusion, renal failure requiring dialysis, thrombocytopenic purpura, used intravenous immunoglobulin within 6 weeks of entry or those that had started new antiretroviral drugs or systematic immunomodulators within 2 weeks of entry.

  • Patients enrolled: 531.

  • Patients randomised: 531.

Leukoreduced red blood concentrates transfusion: 265

Unmodified red blood concentrates transfusion: 266

  • Patients transfused: 521.

  • Patients considered for the analysis: 470.

Main characteristics of patients:

Age: Leukoreduced group = 38.3 ± 8.2 years; Unmodified group = 38.4 ± 8.3 years

Percentage of men: Leukoreduced group = 79%; Unmodified group = 79%

Percentage of antiretroviral therapy‐potent combination: Leukoreduced group = 27%; Unmodified group = 22%

Karnofsky score: Leukoreduced group = 71.4 ± 13.2; Unmodified group = 70.9 ± 12.8

CD4 cells/μL, median: Leukoreduced group = 16 (3 to 71.5); Unmodified group = 12.5(4 to 76)

Interventions

  1. Experimental: Leukoreduced RBC transfusion (pre‐storage leukoreduction)

  2. Control: Unmodified RBC transfusion.

Cointervention: Leukoreduced platelets if was required.

Outcomes

  1. Primary (changed 3 months after beginning of study):

    1. Survival. "...additional resources were obtained to increase accrual to 640 and change the primary clinical end point to survival" (Page 1594).

  2. Secondary:

    1. Time to death.

    2. First serious HIV‐related complication (including specific AIDS‐defining conditions and serious bacterial infections associated with median survival times of < 1 year or an acute mortality > 5%).

    3. Time to new or progressive CMV end organ disease.

    4. Plasma HIV RNA and CMV DNA levels.

    5. Lymphocyte subset markers.

    6. Change in cytokine and lymphocyte activation markers.

Notes

Trial registration: Not reported

Funding: This study was financially supported by Roche Molecular systems and National Heart, Lung and Blood Institute (contract RR00046) (Page 1600).

Role of sponsor: Reagents: Funding/Support: Reagents for detection and quantitation of CMVDNA by polymerase chain reaction were contributed by Roche Molecular Systems (Alameda,Calif). Support provided by National Heart was not detailed

A priori sample size estimation: Yes

Conducted: July 1995 through June 1999

Declared conflicts of interest: Trial authors received research funding from Roche

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "The study was a randomised, double blind, comparative study" (Page 1593).

Quote: "Treatment allocation was made centrally by the study coordinating center, using stratified permuted blocks with dynamic balancing within each center" (Page 1593).

Allocation concealment (selection bias)

Low risk

Quote: "Treatment allocation was made centrally by the study coordinating center, using stratified permuted blocks with dynamic balancing within each center" (Page 1593).

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "The participants, investigators, study coordinators, and persons having any contact with the patients were blinded to study treatment assignments. Blood bank technical staff who prepared the blood products were aware of the treatment assignments" (Page 1593).

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: "The participants, investigators, study coordinators, and persons having any contact with the patients were blinded to study treatment assignments. Blood bank technical staff who prepared the blood products were aware of the treatment assignments" (Page 1593).

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Loss after transfusion: 9.8% (51/521)

Loss after transfusion LR group: 10.8 (28/259)

Loss after transfusion Control group: 8.8% (23/262)

Imbalance between comparison groups: 2%

Selective reporting (reporting bias)

Low risk

Comment: The study protocol is available and all of the study's pre‐specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre‐specified way.

Other bias

Low risk

Comment: The study appears to be free of other sources of bias.

Donati 2014

Methods

Design: Parallel group RCT

Country: Italy

Multicentre study: No

Setting: Hospital

Follow‐up: Not clearly reported, outcomes were measured up to 1 hour after blood transfusion

Unit of allocation: Patients

Unit of analysis: Patients

Participants

Inclusion criteria: Adult patients admitted to ICU of the AOU Ospedali Riuniti of Ancona with sepsis, severe sepsis or septic shock as diagnosed according to standard criteria and requiring blood transfusion for haemoglobin (Hb) levels of less than 8 g/dL or as indicated by the attending physician in accordance with the local hospital guidelines.

Exclusion criteria: Aged < 18 years, previous blood transfusions during ICU stay, previous history of coagulation disorders, cardiogenic or hemorrhagic shock, pregnancy and factors impeding the sublingual microcirculation evaluation (oral surgery and maxillofacial trauma)

  • Patients enrolled: 20

  • Patients randomised: 20

Leukodepleted RBC transfusion: 10

Non‐leukodepleted RBC transfusion: 10

  • Patients transfused: 20

  • Patients considered for the analysis: 20

Main characteristics of patients:

Age: Non‐leukodepleted group = 70 (65 to 72) years; leukodepleted group = 74 (64 to 79) years

Percentage of men: Non‐leukodepleted group = 50%; leukodepleted group = 70%

Interventions

  1. Experimental: Leukodepleted RBC transfusion: leukoreduction was performed by a blood bank physician using the filter Sepacell RZ‐200 (Fenwal, Inc., Lake Zurich, IL, USA) within a maximum of 5 days after donor blood withdrawal (post‐storage leukoreduction).

  2. Control: Non‐leukodepleted RBC transfusion.

Cointervention: Related to sepsis treatment (fluid therapy, vasopressors and inotropic agents, antibiotics, etc.)

Outcomes

  1. Primary:

    1. Microcirculatory Flow Index (MFI) before and after blood transfusion.

  2. Secondary:

    1. Peripheral tissue oxygen saturation (StO2).

    2. Tissue Hb index (THI).

    3. Vascular lumen perfused boundary region (PBR).

    4. Glycocalyx damage markers.

Notes

Trial Registration: NCT01584999

Funding: Not reported

Role of sponsor: Not reported

A priori sample size estimation: Yes

Conducted: February 2011 and 2012

Declared conflicts of interest: One trial author "CI is the inventor of Sidestream Dark Field imaging technology" technique used to measure the outcomes, this author "holds shares in MicroVision Medical and was a consultant for this company more than four years ago but has had no further contact with the company since then. He declares that he has no other competing interests in this field other than his commitment to promoting the importance of the microcirculation during patient care and no other relationships or activities that could appear to have influenced the submitted work. HV holds the position of chief scientific officer in GlycoCheck BV. The other authors declare that they have no competing interests".

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not reported.

Allocation concealment (selection bias)

Low risk

"Blood product randomization was performed through sealed envelopes by a physician at the blood bank" (Page 2).

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

"a physician at the blood bank blindly provided the blood bags to the ICU; neither the attending physician nor the investigators nor the patients were aware of the type of RBCs transfused" (Page 2).

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

"a physician at the blood bank blindly provided the blood bags to the ICU; neither the attending physician nor the investigators nor the patients were aware of the type of RBCs transfused" (Page 2).

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: All patients transfused were analysed.

Patients lost to follow‐up: None.

Selective reporting (reporting bias)

Low risk

Comment: The study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre‐specified.

Other bias

Low risk

Jensen 1996

Methods

Design: Parallel group RCT

Country: Denmark

Multicentre study: Yes (2 university departments of colorectal surgery; page 844).

Setting: Hospital

Follow‐up: 30 days after surgery

Unit of allocation: Patients

Unit of analysis: Patients

Participants

Inclusion criteria: Patients admitted for elective colorectal surgery

Exclusion criteria: < 18 years of age, need for emergency surgery, or immunosuppressive treatment, except steroids

  • Patients enrolled: 589

  • Patients randomised: 589

Leucocyte‐depleted red cells group: 290

Buffy‐coat‐poor red cells group: 299

  • Patients transfused: 260

  • Patients considered for the analysis: 586

Main characteristics of patients:

Age = Median (range): Leucocyte‐depleted red cells group = 69 (35 to 89) years; Buffy‐coat‐poor red cells group = 68 (29 to 92) years

Percentage of men: Leucocyte‐depleted red cells group = 50%; buffy‐coat‐poor red cells group = 48%

Number of procedures: Sigmoid resection: Leucocyte‐depleted red cells group = 11; Buffy‐coat‐poor red cells group = 19

Blood loss = Median (range): Leucocyte‐depleted red cells group = 715 (50 to 3500) mL; Buffy‐coat‐poor red cells group = 805 (10 to 4300) mL.

Interventions

  1. Leucocyte‐depleted red cells group (the timing of leukoreduction is not reported).

  2. Buffy‐coat‐poor red cells group.

Cointervention:

Quote: "All patients received an intravenous dose of cefuroxime 3 g and metronidazole 1.5 g after induction of anaesthesia" (Page 842).

Outcomes

This RCT did not specify by primary or secondary outcomes.

  1. Abdominal wound infection: Accumulation of pus with spontaneous discharge or requiring surgical drainage.

  2. Deep surgical infection: Intraabdominal abscess or septicaemia.

  3. Pneumonia: Fever and infiltrate on chest radiography.

  4. Surgical complications: Anastomotic leakage, abdominal wound dehiscence, intra‐abdominal bleeding and ileus.

  5. Operation‐related mortality: Death during hospital stay or within 30 days after surgery.

Notes

Trial Registration: Not reported.

Funding: Not reported.

Role of sponsor: Not stated.

A priori sample size estimation: Yes.

Conducted: Between January 1992 and January 1995.

Declared conflicts of interest: Not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "were randomly allocated using sealed envelopes to receive either..." (Page 841).

Comment: Insufficient information to permit judgement of ‘low risk’ or ‘high risk’.

Allocation concealment (selection bias)

Unclear risk

Quote: "were randomly allocated using sealed envelopes to receive either..." (Page 841) Use of opaque envelopes is not reported.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Comment: Insufficient information to permit judgement of ‘low risk’ or ‘high risk’.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: "Physicians who were blinded to the transfusion protocol performed follow‐up examinations..." (Page 842).

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: All patients transfused were analysed. (Page 842).

Selective reporting (reporting bias)

Low risk

Comment: The study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre‐specified.

Other bias

Unclear risk

Comment: Sample size estimation took into account loss to follow‐up due to no transfusion.

Lapierre 2007

Methods

Design: Parallel group RCT

Country: France

Multicentre study: No

Setting: Hospital

Follow‐up: 6 months

Unit of allocation: Patients

Unit of analysis: Patients

Participants

Inclusion criteria: "Patients included in the trial were more than 18 years of age and of both sexes and were to undergo surgery for cancer...with a transfusion‐during‐surgery (TdS) risk greater than 30 percent".

Exclusion criteria: "Patients were not eligible for inclusion if they presented contraindications to the use of UN‐RBCs or presented any RBC antibodies and/or anti‐HLA and/or antigranulocyte alloimmunization" (page 1692).

  • Patients enrolled: 161

  • Patients randomised: 37

Unmodified RBCs (UN‐RBC): 19

Leukoreduced RBCs (LR‐RBC): 18

  • Patients transfused: 36

  • Patients considered for the analysis: 35

Main characteristics of patients:

Age = Median (range): Unmodified RBCs group = 56 (40 to 73) years; Leukoreduced RBCs group= 54 (37 to 65) years

Percentage of men: Unmodified RBCs group = 33%; Leukoreduced RBCs group = 47%

Tumour location: Pelvis: Unmodified RBCs group = 11; Leukoreduced RBCs group = 8. Head and neck: Unmodified RBCs group = 6; Leukoreduced RBCs group = 7. Miscellaneous: Unmodified RBCs group = 1; Leukoreduced RBCs group = 2

Blood loss = Median (range): Unmodified RBCs group = 1500 (300 to 3650) mL; Leukoreduced RBCs group = 1325 (300 to 6800) mL

Interventions

  1. Unmodified RBCs.

  2. Leukoreduced RBCs (post‐storage leukoreduction).

Cointervention: Two patients (11%) in the unmodified RBCs group and three patients (18%) received fresh‐frozen plasma. None of the patients received platelet concentrate.

Outcomes

"The main endpoint of the study was to compare immune status in both treatment groups" (page 1692). This was measured through surrogate variables (i.e. microchimerism, peripheral blood cell counts and cytokine production capacity). However, other outcomes were described: "In addition to immune status, other factors compared between the two groups were survival and incidence of nosocomial infection" (page 1694).

Notes

Trial registration: ClinicalTrials database NCT00180869

Funding: "grants from the French Association for Cancer Research (L'Association pour la Recherche sur le Cancer [9653]) and the French Association for Blood Transfusion Research (L'Association pour la Recherche enTransfusion [081997])" (page 1691)

Role of sponsor: Not stated

A priori sample size estimation: Yes

Conducted: between 15 September 1997 and 28 February 1998

Declared conflicts of interest: Not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "The randomization was performed centrally by computer in the Gustave Roussy Cancer Institute Biostatistics Unit after the investigator had sent a fax indicating the minimization factors of the patient" (page 1693).

Allocation concealment (selection bias)

Unclear risk

Comment: Insufficient information to permit judgement of ‘low risk’ or ‘high risk’.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Quote: "Patients and surgeons were not blinded of the treatment allocation" (page 1693).

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Quote: "Patients and surgeons were not blinded of the treatment allocation" (page 1693).

Incomplete outcome data (attrition bias)
All outcomes

Low risk

36 patients were transfused: 18 received unmodified RBCs (UN‐RBC) and 18 received Leukoreduced RBCs (LR‐RBC).

Loss after transfusion: 2.77% (1/36).

Loss after transfusion LR group: 1 died during surgery.

Loss after transfusion Control group: None.

Loss after transfusion. Imbalance between comparison groups: 5%.

Selective reporting (reporting bias)

Unclear risk

Survival after perioperative transfusion is reported in Figure 2. However, number of death is not clearly reported.

Other bias

Unclear risk

Comment: Sample size estimate was calculated based on Th2 polarization. It is unclear what dropout rate was considered in the sample size estimation of 75 participants.

Nathens 2006

Methods

Design: Parallel group RCT

Country: USA

Multicentre study: No

Setting: Hospital

Follow‐up: 28 days after randomisation

Unit of allocation: Patients

Unit of analysis: Patients

Participants

Inclusion criteria: Age of above 17 years and red cell transfusion within 24 hours of injury

Exclusion criteria: Those with an anticipated survival of less than 48 hours, active infection at presentation, receipt of blood products for the current injury before randomisation, individuals with blood group AB Rh negative or B Rh negative, patients with clinically significant red cell alloantibodies requiring an antiglobulin crossmatch, recipients with prior requirements for irradiation, leukoreduction, od CMV protection, subjects enrolled in a concurrent study of pre‐hospital hypertonic saline resuscitation or incarcerated subjects.

  • Patients enrolled: 1864

  • Patients randomised: 1864

Standard transfusion: 935

Leukoreduced transfusion: 929

  • Patients transfused: 515

  • Patients considered for the analysis: 324

Main characteristics of patients included in full analysis.

Age: Standard group = 42.1 ± 18 years; Leukoreduced group = 42.3 ± 19 years

Percentage of men: Standard group = 69%; Leukoreduced group = 66%

Percentage of penetrating injury mechanism: Standard group = 18%; Leukoreduced group = 19%

Injury Severity Score: Standard group = 25.5 ± 11; Leukoreduced group = 23.9 ± 11

Interventions

  1. Leukoreduced transfusion: Prestorage‐Leucoreduced RBC (pre‐storage leukoreduction).

  2. Standard transfusion: Non Prestorage‐Leucoreduced RBC (standard units).

Cointerventions: "All patients received apheresis platelets when platelets were required" (Page 343).

Outcomes

  1. Primary:

    1. Infection within 28 days of randomisation.

  2. Secondary:

    1. Resource use: ventilator days, lengths of hospital stay and length of ICU.

    2. Degree of multiple organ dysfunction.

    3. Mortality.

Note: TRALI was assessed by Watkins 2008 as a secondary analysis.

Notes

Trial registration: www.clinicaltrials.gov, August 23, 2005. Registration No.: NCT00135291

Funding: National Institutes of Health (NIH)

Role of sponsor: The sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review or approval of the manuscript.

A priori sample size estimation: Yes

Conducted: Between 3 February 2003 and 30 August 2004.

Declared conflicts of interest: Not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "The hospital‐based transfusion support service performed the randomization in a 1:1 ratio, using a permuted block scheme (block size of six)" (Page 344).

Allocation concealment (selection bias)

Low risk

Quote: "Using preprinted sealed opaque envelopes containing the study identification number and randomization arm (listed as arm 1 or arm 2) to conceal allocation" (Page 344).

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "Before unit issue, the transfusion service added a Food and Drug Admnistration approved study label to blind the leukoreduction process; the transfusion report accompanying the red cell unit was also blinded" (Page 343).

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: "Before unit issue, the transfusion service added a Food and Drug Admnistration approved study label to blind the leukoreduction process; the transfusion report accompanying the red cell unit was also blinded" (Page 343).

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Loss after transfusion: 5% (16/324).

Loss after transfusion LR group: 7% (11/156).

Loss after transfusion Control group: 3% (5/168).

Imbalance between comparison groups: 4%.

Selective reporting (reporting bias)

Low risk

Comments: The study protocol is available and all of the study's pre‐specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre‐specified way.

Other bias

Low risk

Comment: The study appears to be free of other sources of bias.

Sanfilippo 1985

Methods

Design: Parallel group RCT

Country: USA

Multicentre study: No

Setting: Hospital

Follow‐up: 1 year

Unit of allocation: Patients

Unit of analysis: Patients

Participants

Inclusion criteria: All potential cadaver renal allograft recipients

Exclusion criteria: Not clearly reported

  • Patients enrolled: 126

  • Patients randomised: 107

PRBCs group: 42

Leukocyte poor red cells group: 45

Mixed group: 20

  • Patients transfused: 107

  • Patients considered for the analysis: 107

Main characteristics of patients included in full analysis were not fully stated:

Quote: "there were no significant differences between transfusion groups in terms of demographic factors, including number of transfusions, age, race, sex, degree of HLA match, number of diabetics or the use of ATG posttransplant" (Page 117).

Interventions

  1. PRBCs group: PRBCs.

  2. Leukocyte poor red cells group: Leukocyte poor red cell (the timing of leukoreduction is not reported).

Cointerventions: "All transplant recipients received conventional maintenance immunosuppressive therapy with azathioprine and prednisone, and antithymocyte globulin (ATG) and/or bolus methylprednisolone was used for the treatment of rejection episodes" (Page 117).

Outcomes

This RCT did not specify by primary or secondary outcomes.

  1. Panel reactive antibody (PRA) levels: percent of panel cells showing at least 20% lysis with patients' serum, regardless of serum dilution, as determined by the antiglobulin modification.

  2. Allograft and patient survival.

Notes

Trial registration: Not reported.

Funding: National Kidney Foundation of North Carolina

Role of sponsor: Not stated

A priori sample size estimation: No

Conducted: Between September 1980 and June 1982

Declared conflicts of interest: Not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "...after obtaining informed consent, patients were randomly assigned to receive" (Page 116).

Comment: Insufficient information to permit judgement of ‘low risk’ or ‘high risk’.

Allocation concealment (selection bias)

Unclear risk

Quote: "...after obtaining informed consent, patients were randomly assigned to receive..." (Page 116).

Comment: Insufficient information to permit judgement of ‘low risk’ or ‘high risk’.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Comment: Insufficient information to permit judgement of ‘low risk’ or ‘high risk’.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Comment: Insufficient information to permit judgement of ‘low risk’ or ‘high risk’.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Comment: Insufficient information to permit judgement of ‘low risk’ or ‘high risk’.

Selective reporting (reporting bias)

High risk

Comment: The study report fails to include results for a key outcome that would be expected to have been reported for such a study.

Other bias

High risk

Design bias.

Tartter 1998

Methods

Design: Parallel group RCT

Country: USA

Multicentre study: No

Setting: Hospital

Follow‐up: Unclear. Quote: "Patients were followed up daily in the hospital until discharge (...) and contacted by phone following discharge to elicit possible symptoms of infection".

Unit of allocation: Patients

Unit of analysis: Patients

Participants

Inclusion criteria: Those scheduled for inpatient gastrointestinal surgery under general anaesthesia

Exclusion criteria: Not clearly reported

  • Patients enrolled: 224

  • Patients randomised: 224

Filtered group: 106

Unfiltered group: 118

  • Patients transfused: 59

  • Patients considered for the analysis: 221

Main characteristics of patients:

Age (Unclear if median or mean): Filtered group = 54 years; Unfiltered group = 50 years

Percentage of men: Filtered group = 49%; Unfiltered group = 50%

Hematocrit (Unclear if median or mean): Filtered group = 38; Unfiltered group = 37

Percentage of hypertension: Filtered group = 14%; Unfiltered group = 10%

Percentage of diagnosis of malignancy: Filtered group = 38%; Unfiltered group = 38%

Interventions

  1. Filtered group: Leukocyte‐filtered RBCs (the timing of leukoreduction is not reported).

  2. Unfiltered group: PRBCs.

Cointerventions: "Preoperative preparation included intravenous antibiotics for all patients and bowel cleansing with Golytely for patients in whom transection of the colon or rectum was anticipated" (Page 463)

Outcomes

This RCT did not specify by primary or secondary outcomes.

  1. Postoperative infectious complications: abdominal wound infections, urinary tract infections, Pneumonia, intra‐abdominal collections.

  2. Length of stay

  3. Hospital charges.

Notes

Trial Registration: Not reported.

Funding: Pall Corporation, Gel Cove, NY

Role of sponsor: Not stated.

A priori sample size estimation: Unclear. Trial authors reported the criteria for sample size calculation, including a 60% of dropout rate ("40% of gastrointestinal surgery patients at our institution receive blood transfusions"). The software or method for sample size calculation is not reported. Using the ARCSINUS approximation, and using the same criteria reported by authors, 174 subjects are necessary in first group and 174 in the second to find as statistically significant a proportion difference, expected to be of 0.2 in group 1 and 0.05 in group 2, with an anticipated drop‐out rate of 60%. The study included 224 participants (118 and 106 patients in each group), 59 were transfused (26%) and 50 participants received allogeneic RBC transfusions.

Conducted: Between 1 August 1993 and 31 January 1994

Declared conflicts of interest: Not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Patients were randomly allocated by the study personnel in the blood bank" (Page 463).

Comment: Insufficient information to permit judgement of ‘low risk’ or ‘high risk’.

Allocation concealment (selection bias)

Unclear risk

Comment: Insufficient information to permit judgement of ‘low risk’ or ‘high risk’.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Comment: Insufficient information to permit judgement of ‘low risk’ or ‘high risk’.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Comment: Insufficient information to permit judgement of ‘low risk’ or ‘high risk’.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: all patients transfused were analysed (Page 842).

Selective reporting (reporting bias)

High risk

This RCT did not report mortality.

Comment: The study report fails to include results for a key outcome that would be expected to have been reported for such a study.

Other bias

High risk

Design bias.

Sample size bias. Trial authors reported the criteria for sample size calculation, including a 60% of dropout rate ("40% of gastrointestinal surgery patients at our institution receive blood transfusions"). The software or method for sample size calculation is not reported. Using the ARCSINUS approximation, and using the same criteria reported by the study authors, 174 subjects are necessary in first group and 174 in the second to find as statistically significant a proportion difference, expected to be of 0.2 in group 1 and 0.05 in group 2, with an anticipated drop‐out rate of 60%. The study included 224 participants (118 and 106 patients respectively), 59 were transfused (26%) and 50 participants received allogeneic RBC transfusions.

Titlestad 2001

Methods

Design: Parallel group RCT

Country: Denmark

Multicentre study: No

Setting: Hospital

Follow‐up: 30 days

Unit of allocation: Patients

Unit of analysis: Patients

Participants

Inclusion criteria: Patients admitted —acute and elective— to the Department of Colorectal surgery, undergoing open colorectal surgery

Exclusion criteria: Those receiving blood transfusions within the final 3 months prior to surgery and those below 18 years

  • Patients enrolled: 279

  • Patients randomised: 279

Leukocyte‐depleted erythrocyte suspensions group (LD‐SAGM): 139 patients

Buffycoat‐depleted group: 140 patients

  • Patients transfused: 125 (112 to the allocated group)

  • Patients considered for the analysis: 279

Main characteristics of patients:

Age: Median/range: Leukocyte‐depleted erythrocyte group = 71 (66 to 77) years; Leukocyte‐depleted erythrocyte = 73 (62 to 79) years

Percentage of men: LD‐SAGM group = 51%; Non‐leukocyte‐depleted erythrocyte suspensions (SAGM) group = 60%

Number of malignant colorectal disease: LD‐SAGM group = 37; SAGM group = 56

Hemoglobin: Median/range: LD‐SAGM group = 12.6 (10.6 to 14.2) g/dL; SAGM group = 12.4 (11.1 to 13.9) g/dL

Interventions

  1. Experimental: LD‐SAGM (pre‐storage leukoreduction).

  2. Control: SAGM.

Cointervention: "all patients received perioperative prophylactic antibiotics intravenously (3 g ampicillin or 3 g cefuroxim and 1.5 g metronidazol)" (Page 149).

Platelet transfusion as co‐intervention was not reported

Outcomes

This RCT did not specify by primary or secondary outcomes.

  1. Posooerative infectious complications: Abdominal wound infection, intra‐abdominal abscess, septicaemia, pneumonia.

  2. Non‐infectious surgical complications: Anastomosis leakage, wound rupture, intra‐abdominal bleeding, acute myocardial infarction, deep vein thrombosis, pulmonary embolism, cerebral ischaemic stroke, death.

Notes

Trial registration: Not reported

Funding: Not reported

Role of sponsor: Not reported

A priori sample size estimation: Yes (but not fulfilled)

Conducted: Between May 1997 and November 1999

Declared conflicts of interest: Not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Patients were allocated in the blood bank to receive either..." Page 148.

Comment: Insufficient information to permit judgement of ‘low risk’ or ‘high risk’.

Allocation concealment (selection bias)

Unclear risk

Comment: Insufficient information to permit judgement of ‘low risk’ or ‘high risk’.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "The blood units were supplied by the blood bank, and all units were blinded. White labels were placed on the unit product code numbers, but bar code labels were intact, ensuring safe handling" (Page 149).

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: "Surgeons who were blinded to the transfusion protocol performed the follow‐up examinations" (Page 149).

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Loss after transfusion: 10.4% (13/125).

Loss after transfusion LR group: 12.7 % (7/55).

Loss after transfusion Control group: 8.5% (6/70).

Imbalance between comparison groups: 4.2%.

Selective reporting (reporting bias)

Low risk

The study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre‐specified.

Other bias

High risk

Sample size bias. "Discontinued study due to large exclusions than expected, as well as higher rates of infection, insufficient sample size" (Page 149).

The estimation of sample size bias considered 10% of random error and did not reported it.

Design bias.

Industry bias: Unclear.

van de Watering 1998

Methods

Design: Parallel group RCT

Country: The Netherlands

Multicentre study: No

Setting: Hospital

Follow‐up: 60 days after surgery

Unit of allocation: Patients

Unit of analysis: Patients

Participants

Inclusion criteria: Adults patients undergoing Coronary Artery Bypass grafting (CAGB) surgery, cardiac valve surgery or a combination of both, who had not received blood within the last 6 months.

Exclusion criteria: None clearly reported

  • Patients enrolled: 944

  • Patients randomised: 914

Packed cells without buffy coat: 306

Fresh‐filtered units: 305

Stored‐filtered units: 303

  • Patients transfused: 866

  • Patients considered for the analysis: 914

Main characteristics of patients:

Age: Standard packed cells without buffy coat group = 64.4 ± 9.5 years; Fresh‐filtered units group = 62.9 ± 9.8 years. Stored‐filtered units group = 63.3 ± 9.1 years

Percentage of men: Standard packed cells without buffy coat group = 72%; Fresh‐filtered units group = 74%. SF group = 68%

Percentage of history of myocardial infarction: Standard packed cells without buffy coat group = 50.3%; Fresh‐filtered units group = 44.6%. Stored‐filtered units group = 46.4%

Preoperative Hb: Standard packed cells without buffy coat group = 8.8 ± 0.9 mmol/L; Fresh‐filtered units group = 8.9 ± 0.9 mmol/L. Stored‐filtered units group = 8.8 ± 0.9 mmol/L

Postoperative Hb: Standard packed cells without buffy coat group = 6.6 ± 0.7 mmol/L; Fresh‐filtered units group = 6.6 ± 0.7 mmol/L. Stored‐filtered units group = 6.5 ± 0.7 mmol/L

Interventions

  1. PC trial arm: Standard packed cells without buffy coat.

  2. FF trial arm: Fresh‐filtered units (pre‐storage leukoreduction).

  3. SF trial arm: Stored‐filtered units (post‐storage leukoreduction).

Cointervention: Quote: "Antibiotic prophylaxis was given for 24 hours with CABG and for 48 hours with valve or combined surgery" (Page 563).

Outcomes

  1. Primary:

    1. Incidence of postoperative infections.

    2. HLA antibody formation.

  2. Secondary:

    1. Duration of hospitalisations.

    2. Postoperative mortality within 60 days.

    3. Other postoperative complications.

Notes

Trial registration: Not reported

Funding: NPBI bv, Emmer‐Compascuum, The Netherlands

Role of sponsor: Not reported

A priori sample size estimation: unclear. Trial authors reported the only two criteria for sample size calculation (the proportion expected in each group). The dropout rate expected is not reported.

Conducted: Between March 1992 and August 1994

Declared conflicts of interest: Not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "patients were, by means of a randomizations list at the hospital transfusion service, randomly allocated..." (Page 563).

Allocation concealment (selection bias)

Unclear risk

Comment: Insufficient information to permit judgement of ‘low risk’ or ‘high risk’.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote: "The surgeons and anesthetists were blind to the randomizations result" (Page 563).

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote: "The surgeons and anesthetists were blind to the randomization result" (Page 563).

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: All patients transfused were analysed (Page 567).

Selective reporting (reporting bias)

Low risk

The study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre‐specified.

Other bias

Low risk

van Hilten 2004

Methods

Design: Parallel group RCT

Country: The Netherlands

Multicentre: Yes, 19 hospitals (3 university, 10 clinical, 6 general)

Setting: Hospital

Follow‐up: 15 months

Unit of allocation: Patients

Unit of analysis: Patients

Participants

Inclusion criteria: Patients with ruptured aortic aneurysm elective non‐ruptured AA surgery or gastrointestinal oncology)

Exclusion criteria: Those aged under 18 years, had received transfusions in the three month before the date of randomisation, or had a previous adverse reaction to blood transfusions or had a specific indications for filtered products.

  • Patients enrolled: 1200

  • Patients randomised: 1200

Non‐filtered products: 605

Filtered products: 595

  • Patients transfused: 494

  • Patients considered for the analysis: 1051

Main characteristics of patients allocated to groups (transfused+non‐transfused):

Age: Non‐filtered group = 67 ± 11 years; Filtered group = 66 ± 11.5 years

Percentage of men: Non‐filtered group = 69%; Filtered group = 68%

Percentage of patients transfused: Non‐filtered group = 53%; Filtered group = 51%

Duration of surgery: Non‐filtered group = 210 min; Filtered group = 205 min

Interventions

  1. Experimental group: Filtered RBC transfusions (pre‐storage leukoreduction).

  2. Control group: Non‐filtered RBC transfusions. (buffy coat removed and were plasma reduced).

Outcomes

Primary:

  1. Mortality and duration of stay in intensive care.

Secondary:

  1. Multi‐organ failure.

  2. Infections.

  3. Length of hospital stay.

Notes

Trial registration: www.clinicaltrials.gov, 23 August 2005. Registration No.: NCT00135291

Funding: Health insurance Board, the Netherlands, The National Sanquin Bllod banks.

Role of sponsor: Not reported

A priori sample size estimation: Yes

Conducted: Since June 2000 until December 2001

Declared conflicts of interest: Yes

Note: 22 patients because of administrative and logistic errors. The intake of patients in the study had to be stopped at the end of 2001 because of the implementation of universal leucocyte depletion of RBCs in The Netherlands. This measure was taken by the Dutch Ministry of Health in an effort to reduce the risk of possible transmission of variant Creutzfeldt‐Jacob disease in non‐filtered transfusions.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "randomisation was performed either by telephone (central registration of randomisation) or by opening numbered and sealed envelopes at the hospital blood transfusion services. The transfusion service ensured that the released RBCs appeared identical" (Page 2).

Allocation concealment (selection bias)

Low risk

Quote: "randomisation was performed either by telephone (central registration of randomisation) or by opening numbered and sealed envelopes at the hospital blood transfusion services. The transfusion service ensured that the released RBCs appeared identical" (Page 2).

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "Neither the identity of the patient nor the randomisation group was stored in the main database. The actual randomisation was provided to the statistician only at the final analysis. (Page 2).

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote: "During the study, protocol violations were reported monthly to the national trial office. Patients who received products in violation of randomisation remained in the assigned arm for intention to treat analysis." (Page 2).

Incomplete outcome data (attrition bias)
All outcomes

High risk

Loss after transfusion: 9.35% (51/545).

Loss after transfusion filtered RBC transfusions: 11% (30/267).

Loss after transfusion non‐filtered RBC transfusions: 7.5% (21/278).

Imbalance between comparison groups: 3.5%.

Comment: Missing outcome data are balanced in numbers across study groups. However, reasons for missing outcome data are likely to be related to true outcome (Protocol violations).

Selective reporting (reporting bias)

Low risk

The study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre‐specified.

Other bias

High risk

Design bias.

Wallis 2002

Methods

Design: Parallel group RCT

Country: UK

Multicentre study: No

Setting: Hospital

Follow‐up: 3 months after discharge

Unit of allocation: Patients

Unit of analysis: Patients

Participants

Inclusion criteria: Patients admitted for elective coronary artery bypass grafting or aortic or mitral valve replacement, either singly or in combination

Exclusion criteria: Those with a history of recurrent infections, had a current blood disorder, were taking steroid or other immunosuppressive drugs or received transfusions within the past 12 months

  • Patients enrolled: 597

  • Patients randomised: 597

Plasma reduced group: 198 patients

Buffy coat‐depleted group: 204 patients

WBC filtered group: 195 patients

  • Patients transfused: 509

  • Patients considered for the analysis: 597

Main characteristics of patients (included non‐transfused):

Age: Plasma reduced group = 62.2 ± 9.1 years; Buffy coat‐depleted group = 62.4 ± 8.1 years. WBC filtered group = 61.7 ± 8.6 years

Gender ratio (men to women): Plasma reduced group = 2.9; Buffy coat‐depleted group = 2.6; WBC filtered group= 2.9

Preoperative Hb in g/dL: Plasma reduced group = 14.2 ± 1.2; Buffy coat‐depleted group = 14.1 ± 1.2. WBC filtered group = 14.2 ± 1.2

Discharge Hb in g/dL: Plasma reduced group = 11.3 ± 0.9; Buffy coat‐depleted group = 11.3 ± 1. WBC filtered group = 11.1 ± 0.9

Interventions

  1. Plasma reduced.

  2. Buffy coat‐depleted.

  3. WBC filtered (pre‐storage leukoreduction).

Outcomes

Primary

  1. Events coded as hospital acquired infection.

Secondary:

    1. Length of hospital stay.

    2. Postoperative fever.

    3. Use of antibiotics in hospital.

    4. Evidence of infection after discharge from hospital.

Notes

Trial registration: Not reported

Funding: This study was supported in part by a grant from the Northern and Yorkshire R & D directorate of the National Health Service

Role of sponsor: Not reported

A priori sample size estimation: Yes

Conducted: Not reported

Declared conflicts of interest: Not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Patients were randomly assigned to receive, in the event of a transfusion, PR, BCD, or WCF blood" (Page 1128).

Allocation concealment (selection bias)

Unclear risk

Quote: "Randomization by sealed envelopes was carried out in the hospital blood transfusion department at the time of the admission clinic" (Page 1128). Use of opaque envelopes is not reported.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Quote: "The surgical staff were not blinded as to the blood component given, but were unaware of the randomization when the first decision to transfuse was made" (Page 1128).

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: Collection and review of data to determine postoperative infections and other variables were carried out without knowledge of the randomization or type of blood given" (Page 1128).

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: All patients transfused were analysed.

Selective reporting (reporting bias)

Low risk

The study protocol is unavailable but it is clear that the published reports include all expected outcomes, including those that were pre‐specified (convincing text of this nature may be uncommon).

Other bias

Low risk

Comment: The study appears to be free of other sources of bias.

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Bowden 1995

The study population received other blood components along with or different from PRBC transfusion.

Bracey 2002

Non‐randomised clinical trial.

Connery 2005

Study protocol included patients with no indication of RBCs. Intervention poorly specified.

de Vries 2003

No control group.

de Vries 2004

No transfusion intervention.

Dzik 2002

Study protocol included patients with no indication of RBCs.

Efstathiou 2003

Autologous transfusion as intervention.

Gilbert 1989

The study population received other blood components along with or different from PRBC transfusion.

Gu 1996

The study population received other blood components along with or different from PRBC transfusion.

Gu 2009

Autologous transfusion as intervention.

Hayashi 2000

Autologous transfusion as intervention.

Houbiers 1994

Study protocol included patients with no indication of RBCs.

Jensen 1992

The study population received other blood components along with or different from PRBC transfusion.

Kao 1995

The study population received other blood components along with or different from PRBC transfusion (platelets intervention).

Koskenkari 2005

No transfusion intervention.

Leal‐Noval 2005

No transfusion intervention.

Llewelyn 2004

Non‐randomised clinical trial.

Nielsen 1999

Study protocol included patients with no indication of RBCs.

Opelz 1997

Control group did not receive transfusion.

Salamonsen 2005

No transfusion intervention.

Skånberg 2007

Non‐randomised clinical trial.

So‐Osman 2010

Did not report a control group.

Vamvakas 2007

Meta‐analysis.

van de Watering 2004

Narrative review.

Characteristics of studies awaiting assessment [ordered by study ID]

NCT00810810

Methods

Study design: Parallel group RCT

Allocation: Randomized

Endpoint classification: Efficacy study

Intervention model: Parallel assignment

Masking: Single blind (Investigator)

Primary purpose: Prevention

Participants

Inclusion criteria:

  • At least 18 years of age.

  • Scheduled for open heart surgery of cardiopulmonary bypass that involves: CABG, CABG with valve, aneurysm repair.

  • Urgent or elective surgery.

Exclusion criteria:

  • Scheduled for open heart surgery of cardiopulmonary bypass that involves: placement of a ventricular assist device, cardiac transplantation, aortic dissection repair.

  • Emergent surgery.

  • Participation in other clinical research studies within 30 days of randomisation.

  • Immunosuppressive treatment.

  • Refuse blood transfusion.

  • Disease or condition placing subject at undue risk or decision of attending doctor.

Condition requiring high volume transfusion therapy.

Interventions

Active comparator 1:

Standard blood components

Transfusion, if ordered by physician, with unfiltered RBCs and apheresis platelets

Experimental 2:

Leukoreduced blood components

Transfusion, if ordered by a physician, of leukoreduced RBCs and apheresis platelets

Experimental: 3

Leukoreduced and irradiated

Transfusion, if ordered by physician, of gamma irradiated leukoreduced RBCs and gamma irradiated apheresis platelets

Outcomes

Primary outcomes:

  • Production, de novo, of antibody to HLA antigens (Time frame: 0 to 5 weeks after surgery).

Secondary outcomes:

  • Changes in number or cytokine profile of CD4 T regulatory cells or NKT cells.

(Time frame: 0 to 5 weeks after surgery)

Notes

This study has been completed, but we did not find any publication related to it in the search.

Inclusion or exclusion decision cannot be made because sufficient information is not currently available.

Waghmare 2012

Methods

Study Design: RCT

Allocation: Randomized

Endpoint classification: Efficacy study

Intervention model: Parallel assignment

Masking: Open labeled

Primary purpose: Prevention

Participants

Sixty‐four consecutive ICU. All had severe falciparum malaria and required blood transfusion. Pregnant women and patients with previous blood transfusion were excluded.

Interventions

Filtered group: Leukodepleted blood transfusion using bedside leukodepletion filter versus regular

Control group: non‐leukodepleted blood transfusion

Outcomes

Death from all cases at 28 days, incidence of Acute Respiratory Distress Syndrome and sepsis, severity of multiple organ dysfunction, and length of ICU stay in the two treatment groups.

Patients were studied over 16 months.

Notes

Registration number: Unknown

Inclusion or exclusion decision cannot be made because sufficient information is not currently available.

Zhao 2004

Methods

Study design: RCT

Allocation: Randomized

Endpoint classification: Efficacy study

Intervention model: Parallel assignment

Masking: Unknown

Primary purpose: Prevention

Participants

One hundred patients with cirrhosis of liver, gastric ulcer and cancer were selected to receive RBC concentrates with leukocyte filtration. Another group of 50 patients with liver necrosis, gastric ulcer and cancer were selected to receive non‐filtered RBC concentrates. Two hundred and forty patients with acute or chronic leukaemia, aplastic anaemia, multiple myeloma, thrombocytopenia purpura, diabetes mellitus, cirrhosis of liver, upper gastrointestinal haemorrhage, severe hepatitis, burn and cancer post radioactive or chemical treatment were divided into 2 groups with 120 patients in each one and selected randomly to receive platelet concentrates.

Interventions

RBC concentrates with leukocyte filtration versus non‐filtered RBC concentrates.

Outcomes

incidence rates of febrile nonhaemolytic transfusion reactions (FNHTR).

Notes

Registration number: Unknown.

Inclusion or exclusion decision cannot be made because sufficient information is not currently available.

Data and analyses

Open in table viewer
Comparison 1. Leukoreduced PRBC versus non‐leukoreduced PRBC. Main analysis (randomised patients)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 TRALI. Number of events of the total of randomised patients reported Show forest plot

1

1864

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.67, 1.36]

Analysis 1.1

Comparison 1 Leukoreduced PRBC versus non‐leukoreduced PRBC. Main analysis (randomised patients), Outcome 1 TRALI. Number of events of the total of randomised patients reported.

Comparison 1 Leukoreduced PRBC versus non‐leukoreduced PRBC. Main analysis (randomised patients), Outcome 1 TRALI. Number of events of the total of randomised patients reported.

2 Death. Number of events of the total of randomised patients reported Show forest plot

9

6485

Risk Ratio (M‐H, Random, 95% CI)

0.81 [0.58, 1.12]

Analysis 1.2

Comparison 1 Leukoreduced PRBC versus non‐leukoreduced PRBC. Main analysis (randomised patients), Outcome 2 Death. Number of events of the total of randomised patients reported.

Comparison 1 Leukoreduced PRBC versus non‐leukoreduced PRBC. Main analysis (randomised patients), Outcome 2 Death. Number of events of the total of randomised patients reported.

3 Infection. Number of events of the total of randomised patients reported Show forest plot

10

6709

Risk Ratio (M‐H, Random, 95% CI)

0.80 [0.62, 1.03]

Analysis 1.3

Comparison 1 Leukoreduced PRBC versus non‐leukoreduced PRBC. Main analysis (randomised patients), Outcome 3 Infection. Number of events of the total of randomised patients reported.

Comparison 1 Leukoreduced PRBC versus non‐leukoreduced PRBC. Main analysis (randomised patients), Outcome 3 Infection. Number of events of the total of randomised patients reported.

4 Adverse events. Number of events of the total of randomised patients reported Show forest plot

2

634

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.64, 1.02]

Analysis 1.4

Comparison 1 Leukoreduced PRBC versus non‐leukoreduced PRBC. Main analysis (randomised patients), Outcome 4 Adverse events. Number of events of the total of randomised patients reported.

Comparison 1 Leukoreduced PRBC versus non‐leukoreduced PRBC. Main analysis (randomised patients), Outcome 4 Adverse events. Number of events of the total of randomised patients reported.

4.1 Fever

2

634

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.64, 1.02]

Open in table viewer
Comparison 2. Leukoreduced PRBC versus non‐leukoreduced PRBC. Secondary analysis (transfused patients)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 TRALI. Number of events of the total of transfused patients reported Show forest plot

1

268

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.74, 1.29]

Analysis 2.1

Comparison 2 Leukoreduced PRBC versus non‐leukoreduced PRBC. Secondary analysis (transfused patients), Outcome 1 TRALI. Number of events of the total of transfused patients reported.

Comparison 2 Leukoreduced PRBC versus non‐leukoreduced PRBC. Secondary analysis (transfused patients), Outcome 1 TRALI. Number of events of the total of transfused patients reported.

2 Death. Number of events of the total of transfused patients reported Show forest plot

10

4060

Risk Ratio (M‐H, Random, 95% CI)

0.80 [0.60, 1.07]

Analysis 2.2

Comparison 2 Leukoreduced PRBC versus non‐leukoreduced PRBC. Secondary analysis (transfused patients), Outcome 2 Death. Number of events of the total of transfused patients reported.

Comparison 2 Leukoreduced PRBC versus non‐leukoreduced PRBC. Secondary analysis (transfused patients), Outcome 2 Death. Number of events of the total of transfused patients reported.

3 Infection. Number of events of the total of transfused patients reported Show forest plot

10

3557

Risk Ratio (M‐H, Random, 95% CI)

0.76 [0.58, 1.00]

Analysis 2.3

Comparison 2 Leukoreduced PRBC versus non‐leukoreduced PRBC. Secondary analysis (transfused patients), Outcome 3 Infection. Number of events of the total of transfused patients reported.

Comparison 2 Leukoreduced PRBC versus non‐leukoreduced PRBC. Secondary analysis (transfused patients), Outcome 3 Infection. Number of events of the total of transfused patients reported.

4 Adverse events. Number of events of the total of transfused patients reported Show forest plot

2

544

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.60, 0.94]

Analysis 2.4

Comparison 2 Leukoreduced PRBC versus non‐leukoreduced PRBC. Secondary analysis (transfused patients), Outcome 4 Adverse events. Number of events of the total of transfused patients reported.

Comparison 2 Leukoreduced PRBC versus non‐leukoreduced PRBC. Secondary analysis (transfused patients), Outcome 4 Adverse events. Number of events of the total of transfused patients reported.

4.1 Fever

2

544

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.60, 0.94]

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies.
Figures and Tables -
Figure 2

'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies.

'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study.
Figures and Tables -
Figure 3

'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study.

TSA calculated to reliably detect a 25% relative change in the incidence of death from any cause, assuming a control group event rate of 9.34% with a power of 80% at an alpha of 5%
Figures and Tables -
Figure 4

TSA calculated to reliably detect a 25% relative change in the incidence of death from any cause, assuming a control group event rate of 9.34% with a power of 80% at an alpha of 5%

Funnel plot of comparison: 1 Leukoreduced PRBC versus non‐leukoreduced PRBC. Main Analysis (Randomised patients), outcome: 1.3 Infection. Number of events of the total of randomised patients reported.
Figures and Tables -
Figure 5

Funnel plot of comparison: 1 Leukoreduced PRBC versus non‐leukoreduced PRBC. Main Analysis (Randomised patients), outcome: 1.3 Infection. Number of events of the total of randomised patients reported.

TSA calculated to reliably detect a 25% relative change in the incidence of infection from any cause, assuming a control group event rate of 20.4% with a power of 80% at an alpha of 5%.
Figures and Tables -
Figure 6

TSA calculated to reliably detect a 25% relative change in the incidence of infection from any cause, assuming a control group event rate of 20.4% with a power of 80% at an alpha of 5%.

TSA calculated to reliably detect a 25% relative change in the incidence of fever, assuming a control group event rate of 38.7% with a power of 80% at an alpha of 5%.
Figures and Tables -
Figure 7

TSA calculated to reliably detect a 25% relative change in the incidence of fever, assuming a control group event rate of 38.7% with a power of 80% at an alpha of 5%.

Comparison 1 Leukoreduced PRBC versus non‐leukoreduced PRBC. Main analysis (randomised patients), Outcome 1 TRALI. Number of events of the total of randomised patients reported.
Figures and Tables -
Analysis 1.1

Comparison 1 Leukoreduced PRBC versus non‐leukoreduced PRBC. Main analysis (randomised patients), Outcome 1 TRALI. Number of events of the total of randomised patients reported.

Comparison 1 Leukoreduced PRBC versus non‐leukoreduced PRBC. Main analysis (randomised patients), Outcome 2 Death. Number of events of the total of randomised patients reported.
Figures and Tables -
Analysis 1.2

Comparison 1 Leukoreduced PRBC versus non‐leukoreduced PRBC. Main analysis (randomised patients), Outcome 2 Death. Number of events of the total of randomised patients reported.

Comparison 1 Leukoreduced PRBC versus non‐leukoreduced PRBC. Main analysis (randomised patients), Outcome 3 Infection. Number of events of the total of randomised patients reported.
Figures and Tables -
Analysis 1.3

Comparison 1 Leukoreduced PRBC versus non‐leukoreduced PRBC. Main analysis (randomised patients), Outcome 3 Infection. Number of events of the total of randomised patients reported.

Comparison 1 Leukoreduced PRBC versus non‐leukoreduced PRBC. Main analysis (randomised patients), Outcome 4 Adverse events. Number of events of the total of randomised patients reported.
Figures and Tables -
Analysis 1.4

Comparison 1 Leukoreduced PRBC versus non‐leukoreduced PRBC. Main analysis (randomised patients), Outcome 4 Adverse events. Number of events of the total of randomised patients reported.

Comparison 2 Leukoreduced PRBC versus non‐leukoreduced PRBC. Secondary analysis (transfused patients), Outcome 1 TRALI. Number of events of the total of transfused patients reported.
Figures and Tables -
Analysis 2.1

Comparison 2 Leukoreduced PRBC versus non‐leukoreduced PRBC. Secondary analysis (transfused patients), Outcome 1 TRALI. Number of events of the total of transfused patients reported.

Comparison 2 Leukoreduced PRBC versus non‐leukoreduced PRBC. Secondary analysis (transfused patients), Outcome 2 Death. Number of events of the total of transfused patients reported.
Figures and Tables -
Analysis 2.2

Comparison 2 Leukoreduced PRBC versus non‐leukoreduced PRBC. Secondary analysis (transfused patients), Outcome 2 Death. Number of events of the total of transfused patients reported.

Comparison 2 Leukoreduced PRBC versus non‐leukoreduced PRBC. Secondary analysis (transfused patients), Outcome 3 Infection. Number of events of the total of transfused patients reported.
Figures and Tables -
Analysis 2.3

Comparison 2 Leukoreduced PRBC versus non‐leukoreduced PRBC. Secondary analysis (transfused patients), Outcome 3 Infection. Number of events of the total of transfused patients reported.

Comparison 2 Leukoreduced PRBC versus non‐leukoreduced PRBC. Secondary analysis (transfused patients), Outcome 4 Adverse events. Number of events of the total of transfused patients reported.
Figures and Tables -
Analysis 2.4

Comparison 2 Leukoreduced PRBC versus non‐leukoreduced PRBC. Secondary analysis (transfused patients), Outcome 4 Adverse events. Number of events of the total of transfused patients reported.

Summary of findings for the main comparison. Leukoreduced PRBCs versus non‐leukoreduced PRBCs for preventing adverse reaction from allogeneic blood transfusion

Leukoreduced PRBCs versus non‐leukoreduced PRBCs for preventing adverse reaction from allogeneic blood transfusion

Patient or population: Patients receiving RBC transfusion
Settings: Any
Intervention: Leukoreduced PRBCs
Comparison: Non‐leukoreduced PRBCs

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Non‐leukoreduced packed RBCs

Leukoreduced packed RBCs

TRALI
Follow‐up: mean 28 days

Study population

RR 0.96
(0.67 to 1.36)

1864
(1 study)

⊕⊕⊝⊝
low1

TSA yielded an inconclusive result.

63 per 1000

61 per 1000
(42 to 86)

Death due to any cause
Follow‐up: median 2.5 months

Study population

RR 0.81
(0.58 to 1.12)

6485
(9 studies)

⊕⊝⊝⊝
very low2

TSA yielded an inconclusive
result.

93 per 1000

76 per 1000
(54 to 104)

Infection from any cause
Follow‐up: mean 2.5 months

Study population

RR 0.80
(0.62 to 1.03)

6709
(10 studies)

⊕⊝⊝⊝
very low3

TSA yielded an inconclusive
result.

204 per 1000

163 per 1000
(127 to 210)

Adverse events
Follow‐up: mean 3 months

Study population

RR 0.81
(0.64 to 1.02)

634
(2 studies)

⊕⊕⊝⊝
low4

TSA yielded an inconclusive
result.

387 per 1000

314 per 1000
(248 to 395)

Non‐infectious complication

Study population

Not estimable

No trial assessed this outcome.

Not estimable

Not estimable

*The basis for the assumed risk was the median control group risk across studies. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio; TRALI: Transfusion‐related acute lung injury; RBC: Red blood cell; PRBC: Packed red blood cell; DARIS: Diversity‐adjusted required information size.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Downgraded by two due to imprecision: small sample size as compared with the calculated DARIS and the wide CI overlapping zones of no effect, as well as potential harm or benefit, or both. Few events reported.
2Downgraded due to: high risk of bias (Six of nine included studies have high or unclear risk of bias. ‐1); important heterogeneity (I² statistic: 63%, ‐1); and imprecision as reflected in the wide CI and an insufficient accrued information size compared with the DARIS (‐1).

3Downgraded due to: high risk of bias (Seven of 10 included studies were at high or unclear risk of bias, ‐1); important heterogeneity (I² statistic: 84%, ‐2); and imprecision due to the CI crossing the threshold of meaningful effect and an insufficient sample size as compared with the DARIS (‐1)

4Downgraded due to: high risk of bias (All included studies evaluated were at high risk of bias, ‐1) and imprecision due to the CI crossing the threshold of meaningful effect and an insufficient sample size as compared with the DARIS (‐1).

Figures and Tables -
Summary of findings for the main comparison. Leukoreduced PRBCs versus non‐leukoreduced PRBCs for preventing adverse reaction from allogeneic blood transfusion
Comparison 1. Leukoreduced PRBC versus non‐leukoreduced PRBC. Main analysis (randomised patients)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 TRALI. Number of events of the total of randomised patients reported Show forest plot

1

1864

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.67, 1.36]

2 Death. Number of events of the total of randomised patients reported Show forest plot

9

6485

Risk Ratio (M‐H, Random, 95% CI)

0.81 [0.58, 1.12]

3 Infection. Number of events of the total of randomised patients reported Show forest plot

10

6709

Risk Ratio (M‐H, Random, 95% CI)

0.80 [0.62, 1.03]

4 Adverse events. Number of events of the total of randomised patients reported Show forest plot

2

634

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.64, 1.02]

4.1 Fever

2

634

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.64, 1.02]

Figures and Tables -
Comparison 1. Leukoreduced PRBC versus non‐leukoreduced PRBC. Main analysis (randomised patients)
Comparison 2. Leukoreduced PRBC versus non‐leukoreduced PRBC. Secondary analysis (transfused patients)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 TRALI. Number of events of the total of transfused patients reported Show forest plot

1

268

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.74, 1.29]

2 Death. Number of events of the total of transfused patients reported Show forest plot

10

4060

Risk Ratio (M‐H, Random, 95% CI)

0.80 [0.60, 1.07]

3 Infection. Number of events of the total of transfused patients reported Show forest plot

10

3557

Risk Ratio (M‐H, Random, 95% CI)

0.76 [0.58, 1.00]

4 Adverse events. Number of events of the total of transfused patients reported Show forest plot

2

544

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.60, 0.94]

4.1 Fever

2

544

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.60, 0.94]

Figures and Tables -
Comparison 2. Leukoreduced PRBC versus non‐leukoreduced PRBC. Secondary analysis (transfused patients)