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Transfusion-Related Immunomodulation in Relation to Perioperative Infection/Cancer: Biology, Evidence, and Controversy in Transfusion

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Essentials of Blood Product Management in Anesthesia Practice

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Abstract

Transfusion-related immunomodulation is a side effect of allogeneic transfusion. During the development of orthotopic renal transplantation, red cell transfusions were administered as an effective immunosuppressant. In the 1980s–90s, the focus and lay hysteria was on viral transmission (hepatitis and AIDS) as risks for blood transfusion. These viral risks are now reduced to very low levels and evidence has emerged that transfusion-related immunomodulation contributes to a number of adverse outcomes associated with allogeneic transfusion. Controversy remains due to the largely retrospective data published. This review will outline historical perspectives as well as look into mechanisms and outcomes. It is important to understand the controversy so that research going forward may be well focused and evidence based.

The work contained within is solely the author’s own and each has contributed from conception through writing and reviewing.

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References

  1. Ellingson KD, Sapiano MRP, Haass KA, et al. Continued decline of blood collection and transfusion in the United States-2015. Transfusion. 2017;57:1588–98.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Edens C, Haass KA, Cumming M, et al. Evaluation of the National Healthcare Safety Network Hemovigilance Module for transfusion-related adverse reactions in the United States. Transfusion. 2019;59:524–33.

    Article  PubMed  Google Scholar 

  3. Block TM, Alter HJ, London WT, Bray M. A historical prospective on the discovery and elucidation of the hepatitis B virus. Antivir Res. 2016;131:109–23.

    Article  CAS  PubMed  Google Scholar 

  4. Stramer SL. Current perspectives in transfusion-transmitted infectious diseases: emerging and re-emerging infections. ISBT Sci Ser. 2014;9:30–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Perrotta PL, Snyder EL. Non- infectious complications of transfusion therapy. Blood Rev. 2001;15:69–83.

    Article  CAS  PubMed  Google Scholar 

  6. Hendrickson JE, Hillyer CD. Noninfectious serious hazards of transfusion. Anesth Analg. 2009;108:759–69.

    Article  PubMed  Google Scholar 

  7. Gilliss BM, Looney MR, Gropper MA. Reducing non-infectious risks of blood transfusion. Anesthesiology. 2011;115:635–49.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Harvey AR, Basavaraju S, Chung KW, Kuehnert M. Transfusion-related adverse reactions reported to the National Healthcare Safety network Hemovigilance Module, United States 2010–2012. Transfusion. 2015;55:709–18.

    Article  PubMed  Google Scholar 

  9. Manoukian S, Stewart S, Dancer S, et al. Estimating excess length of stay due to healthcare-associated infections: a systemic review and meta-analysis of statistical methodology- Review. J Hosp Acquir Infect. 2018;100:222–35.

    Article  CAS  Google Scholar 

  10. Opelz G, Sengar DP, Mickey MR, Terasaki PI. Effect of blood transfusions on subsequent kidney transplants. Transplant Proc. 1973;5:253–9.

    CAS  PubMed  Google Scholar 

  11. Morris PJ, Ting A, Stocker J. Leukocyte antigens in renal transplantation. 1. The paradox of blood transfusions in renal transplantation. Med J Aust. 1968;24:1088–90.

    Article  Google Scholar 

  12. Fabre JW, Morris PJ. The mechanism of specific immunosuppression of renal allograft rejection by donor strain blood. Transplantation. 1972;14:634–40.

    Article  CAS  PubMed  Google Scholar 

  13. Thoenes GH, Pielsticker K, Schreiber MA. Blood transfusion-induced facilitation of kidney graft survival in rats (congenic-resistant strains). Clin Nephrol. 1980;13:133–41.

    CAS  PubMed  Google Scholar 

  14. Keowan PA, Descamps B. Improved renal allograft survival after blood transfusion: a non-specific, erythrocyte-mediated immunoregulatory process? Lancet. 1979;8106:20–2.

    Article  Google Scholar 

  15. Gatenby PA, Cameron K, Simes RJ, Adelstein S, Bennett MJ, Jansen RP, Shearman RP, Stewart GJ, Whittle M, Doran TJ. Treatment of recurrent spontaneous abortion by immunization with paternal lymphocytes: results of a controlled trial. Am J Reprod Immunol. 1993;29:88–94.

    Article  CAS  PubMed  Google Scholar 

  16. Gantt CL. Red blood cells for cancer patients. Lancet. 1981;2:363.

    Article  CAS  PubMed  Google Scholar 

  17. Murphy P, Heal JM, Blumberg N. Infection or suspected infection after hip replacement surgery with autologous or homologous blood transfusions. Transfusion. 1991;31:212–7.

    Article  CAS  PubMed  Google Scholar 

  18. 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;348:841–5.

    Article  CAS  PubMed  Google Scholar 

  19. van de Watering LMG, Hermans J, Houbiers JGA, van den Broek PJ, Bouter H, Boer F, Harvey MS, Huysmans HA, Brand A. Beneficial effect of leukocyte depletion of transfused blood on post-operative complications in patients undergoing cardiac surgery: a randomized clinical trial. Circulation. 1998;97:562–8.

    Article  PubMed  Google Scholar 

  20. Vamvakas EC, Blajchman MA. Transfusion-related immunomodulation (TRIM): an update. Blood Rev. 2007;21:327–48.

    Article  PubMed  Google Scholar 

  21. Kao KJ. Induction of humoral immune tolerance to major histocompatibility complex antigens by transfusions of UV-B irradiated leukocytes. Blood. 1996;88:4375–82.

    Article  CAS  PubMed  Google Scholar 

  22. Bordin JO, Heddle NM, Blajchman MA. Biologic effects of leukocytes present in transfused cellular blood products. Blood. 1994;84:1705–21.

    Article  Google Scholar 

  23. Blajchman MA, Bardossy I, Carmen R, Sastry A, Singal DP. Allogeneic blood transfusion-induced enhancement of tumor growth: two animal models showing amelioration by leukodepletion and passive transfer using spleen cells. Blood. 1993;81:1880–2.

    Article  CAS  PubMed  Google Scholar 

  24. Clark DA, Gorczynski RM, Blajchman MA. Transfusion-related immunomodulation due to peripheral blood dendritic cells expressing the CD200 tolerance signaling molecule and alloantigen. Transfusion. 2008;48:814–21.

    Article  PubMed  Google Scholar 

  25. Reed SG. TGF-β in infections and infectious disease. Microbes Infect. 1999;1:1313–25.

    Article  CAS  PubMed  Google Scholar 

  26. Beko KR, Tran HO, Hewitt CW, Black KS, Patel MP, Ramsamooj R, Martin DC. Mechanisms of prior blood transfusion-cyclosporine-induced tolerance: a potential role for immune-cellular chimerism. Transplant Proc. 1991;23:147–8.

    PubMed  Google Scholar 

  27. Dzik WH. Mononuclear cell microchimerism and the immunomodulatory effect of transfusion. Transfusion. 1994;34:1007–12.

    Article  CAS  PubMed  Google Scholar 

  28. Kirkley SA, Cowles J, LPelligrini Jr VD, Harris CM, Boyd AD, Blumberg N. Blood transfusion and total joint replacement surgery: T-helper 2 cytokine secretion and clinical outcome. Transf Med. 1998;8:195–204.

    Article  CAS  Google Scholar 

  29. Gafter U, Kalechman Y, Sredni B. Blood transfusion enhances production of T-helper-2 cytokines and transforming growth factor beta in humans. Clin Sci (Lond). 1996;91:519–23.

    Article  CAS  Google Scholar 

  30. Utter GH, Lee TH, Rivers RM, Montalvo L, Wen L, Chafets DM, Reed WF, Busch MP. Microchimerism decades after transfusion among combat-injured US veterans from the Vietnam, Korean, and World War II conflicts. Transfusion. 2008;48:1609–15.

    Article  PubMed  Google Scholar 

  31. Nelson JL. HLA relationships of pregnancy, microchimerism and autoimmune disease. J Reprod Immunol. 2001;52:77–84.

    Article  CAS  PubMed  Google Scholar 

  32. Reed W, Lee TH, Norris PJ, Utter GH, Busch MP. Transfusion-associated microchimerism: a new complication of blood transfusions in severely ill patients. Semin Hematol. 2007;44:24–31.

    Article  PubMed  Google Scholar 

  33. Nielsen HJ, Reimert CM, Pedersen AN, Brünner N, Edvardsen L, Dybkjaer E, Kehlet H, Skov PS. Time-dependent, spontaneous release of white cell- and platelet-derived bioactive substances from stored human blood. Transfusion. 1996;36:960–5.

    Article  CAS  PubMed  Google Scholar 

  34. Ghio M, Contini P, Mazzei C, Brenci S, Barberis G, Filaci G, Indiveri F, Puppo F. Soluble HLA class I, HLA class II, and Fas ligand in blood components: a possible key to explain the immunomodulatory effects of allogeneic blood transfusion. Blood. 1999;93:1770–7.

    Article  CAS  PubMed  Google Scholar 

  35. Puppo F, Contini P, Ghio M, Brenci S, Scudeletti M, Filaci G, Ferrone S, Indiveri F. Soluble human MHC class I molecules induce soluble Fas-ligand secretion and trigger apoptosis in activated CD8+ Fas (CD95)+ T lymphocytes. Int Immunol. 2000;12:195–203.

    Article  CAS  PubMed  Google Scholar 

  36. Magee CC, Sayegh MH. Peptide-mediated immunosuppression. Curr Opin Immunol. 1997;9:669–75.

    Article  CAS  PubMed  Google Scholar 

  37. Roelen DL, van Rood JJ, Brand A, Claas FH. Immunomodulation by blood transfusions. Vox Sang. 2000;78:273–5.

    PubMed  Google Scholar 

  38. Brunson ME, Alexander JW. Mechanisms of transfusion-induced immunosuppression. Transfusion. 1990;30:651–8.

    Article  CAS  PubMed  Google Scholar 

  39. Vamvakas EC, Blajchman MA. Deleterious clinical effects of transfusion-associated immunomodulation: fact or fiction? [review]. Blood. 2001;97:1180–95.

    Article  CAS  PubMed  Google Scholar 

  40. 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;42:1127–34.

    Article  CAS  PubMed  Google Scholar 

  41. 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. Int J Color Dis. 2001;16:147–53.

    Article  CAS  Google Scholar 

  42. Blumberg N. Deleterious clinical effects of transfusion immunomodulation: proven beyond a reasonable doubt. Transfusion. 2005;45:33S–9; discussion 39S–40.

    Article  PubMed  Google Scholar 

  43. Fergusson D, Aaron SD, Guyatt G, Hebert P. Post-randomization exclusions: the intention to treat principle and excluding patients from analysis. BMJ. 2002;325:652–4.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Blumberg N, Zhao H, Wang H, Messing S, Heal JM, Lyman GH. The intention to treat principle in clinic trials and meta-analysis of leukoreduced blood transfusion in surgical patients. Transfusion. 2007;47:573–81.

    Article  PubMed  Google Scholar 

  45. Kwon S, Lew S, Chamberlain RS. Leukocyte filtration and postoperative infections. J Surg Res. 2016;205:499–509.

    Article  CAS  PubMed  Google Scholar 

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Conflict of Interest

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Author information

Authors and Affiliations

  1. Vanderbilt University Medical Center, Department of Anesthesiology, Nashville, TN, USA

    Atish Patel

  2. University of Florida Health, Gainesville, FL, USA

    Bruce D. Spiess

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  1. Atish Patel
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  2. Bruce D. Spiess
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Corresponding author

Correspondence to Atish Patel .

Editor information

Editors and Affiliations

  1. NYU-Grossman School of Medicine, Department of Anesthesiology, New York, NY, USA

    Corey S. Scher

  2. Departments of Anesthesiology and Pharmacology Toxicology, and Neurosciences, Louisiana State University School of Medicine-Shreveport, Shreveport, LA, USA

    Alan David Kaye

  3. Department of Anesthesiology and Perioperative Medicine, Milton S. Hershey Medical Center, Penn State College of Medicine, Hershey, PA, USA

    Henry Liu

  4. NYU Grossman School of Medicine, Department of Anesthesiology, Perioperative Care and Pain Medicine, New York, NY, USA

    Seth Perelman

  5. NYU-Grossman School of Medicine, Department of Anesthesiology, New York, NY, USA

    Sarah Leavitt

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Patel, A., Spiess, B.D. (2021). Transfusion-Related Immunomodulation in Relation to Perioperative Infection/Cancer: Biology, Evidence, and Controversy in Transfusion. In: Scher, C.S., Kaye, A.D., Liu, H., Perelman, S., Leavitt, S. (eds) Essentials of Blood Product Management in Anesthesia Practice. Springer, Cham. https://doi.org/10.1007/978-3-030-59295-0_31

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  • DOI: https://doi.org/10.1007/978-3-030-59295-0_31

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  • Publisher Name: Springer, Cham

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  • Online ISBN: 978-3-030-59295-0

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