Transfusion-related immunomodulation

Transfusion-related immunomodulation

Transfusion-related immunomodulation refers to the transient depression of the immune system following transfusion of blood products. This effect has been recognized in groups of individuals who have undergone kidney transplantation or have had multiple miscarriages. [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 Mar;29(2):88-94. PMID 8329110] Some research studies have shown that, because of this immune depression, blood transfusions increase the risk of infections and cancer recurrence. However, other studies have not shown these differences and the degree of impact transfusion has on infection and tumor recurrence is not well understood. [Goodnough LT, Brecher ME, Kanter MH, AuBuchon JP. "Transfusion medicine. First of two parts--blood transfusion." N Engl J Med. 1999 Feb 11;340(6):438-47. Review. PMID 9971869] The Blood Products Advisory Committee of the Food and Drug Administration recommends that all transfused blood products undergo leukocyte reduction in order to offset the contribution of donor white blood cells to immune suppression. [American Association of Blood Banks. "BPAC recommends universal leukoreduction." AABB News Briefs 1998;20(11):16.]


The topic of transfusion immunomodulation (the "related" is redundant and thus unnecessary) is actually of considerably greater importance in medicine and broader in scope than one might think. With the exception of life threatening hemorrhage, the only convincing evidence for the benefit of transfusion therapy as currently practiced is in preventing recurrent stroke in sickle cell disease. The rest of medical uses of transfusion remain of uncertain benefit to risk ratio. What has been definitively demonstrated is that in most clinical situations, the patients who are transfused do considerably worse than those not transfused and those who get more transfusions almost always do worse than those getting fewer transfusions. While some of this effect is due to ascertainment bias (sicker patients get transfused or receive more transfusions), the cause and effect nature of these observations is virtually certain. Some of the effects demonstrating some or all the conditions for cause and effect (dose dependence, reproducibility, biologic plausibility, etc.) include increased post-operative infections (ameliorated in part by leukoreduction or use of autologous transfusions in randomized trials), increased allograft survival, decreased spontaneous abortions, decreased severity of inflammatory bowel disease, increased acute lung injury, increased myocardial infarction and other thrombotic complications, etc. Thus transfusion immunomodulation has been broadened to encompass not only decreases in cellular adaptive immunity but inappropriate activation of innate inflammatory immunity and the hemostatic system, including platelets. Fortunately, some of these effects can in part be mitigated by leukoreduction of blood transfusions or avoidance of blood transfusions. Additional promising preliminary research demonstrates that removal of supernatant plasma from stored transfusions may have beneficial effects. Clearly there are both cells and small molecule biologic mediators in stored donor blood that modulate not only recipient immune function, but hemostatic and organ specific functions. This is one of the more important research agendas in transfusion medicine in terms of clinical outcomes for patients, which has been recognized by the NIH directing its research funds into this area of research beginning in 2008.

For a recent history of this subject, see the commentary below.

Blumberg N.Deleterious clinical effects of transfusion immunomodulation: proven beyond a reasonable doubt.Transfusion. 2005 Aug;45(2 Suppl):33S-39S.

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