Chapter 468 Risks of Blood Transfusions

The greatest risk of a blood transfusion is receiving a transfusion intended for another patient. This risk is particularly high for infants, because identification bands may not be attached to their bodies, difficulties in drawing pretransfusion compatibility testing blood sample may lead to deviations in usual policies, and infants cannot speak to identify themselves. Thus, particular care must be taken to ensure accurate patient and blood sample identification.

Although the risks of allogeneic blood transfusions are low, transfusions must be given judiciously. Taking nucleic acid amplification testing (NAT) and all other donor-screening activities (antibody and epidemiology screening) into account, a current estimate of the risk of transfusion-associated HIV is approximately one per every 2,000,000 donor exposures. Similarly, with NAT, the risk of viral hepatitis C is one per every 1,500,000 to 2,000,000 donor exposures (Table 468-1). NAT identifies circulating viral material in the window period before antibodies develop and is used to detect HIV, hepatitis C, and West Nile virus. NAT is also available for hepatitis B, but its use for this purpose is variable and controversial.

Table 468-1 ESTIMATED RISKS IN TRANSFUSION PER UNIT TRANSFUSED IN THE USA

	ESTIMATED RISK
Febrile reaction	1/300
Urticaria or other cutaneous reaction	1/50-100
Red blood cell alloimmunization	1/100
Mistranfusion	1/14,000-19,000
Hemolytic reaction	1/6,000
Fatal hemolysis	1/1,000,000
Transfusion-associated lung injury	1/5,000
HIV1 and HIV2	1/2,000,000-3,000,000
Hepatitis B	1/100,000-200,000
Hepatitis C	1/1,000,000-2,000,000
Human T-cell lymphotrophic virus (HTLV) I and II	1/641,000
Bacterial contamination	1/5,000,000
Malaria	1/4,000,000
Anaphylaxis	1/20,000-50,000
Graft versus host disease	Uncommon
Immunomodulation	Unknown

From Klein HG, Spahn DR, Carson JL: Red blood cell transfusion in clinical practice, Lancet 370:415–426, 2007.

Transfusion-associated cytomegalovirus (CMV) can be nearly eliminated by transfusion of leukocyte reduced cellular blood products or by selection of blood from donors who are seronegative for antibody to cytomegalovirus. Although it is logical to hypothesize that first collecting blood components from CMV-seronegative donors and then removing the white blood cells (WBCs) might improve safety, no data are available to document the efficacy of this combined approach. Moreover, findings from one study suggest that this combined approach, surprisingly, may be incorrect. Large quantities of CMV are present “free” in the plasma of healthy-appearing donors during primary infection (while CMV antibodies are either still absent or are newly emerging), rather than being leukocyte associated as they are during latent infection, when substantial quantities of antibodies are present. Thus, virus will not be removed by leukocyte reduction, and donors will be misclassified as CMV seronegative because antibody is below the limits of detection in window-phase or early infection. Because nearly all plasma CMV disappears after donors are seropositive for CMV antibody for several months and the virus is almost exclusively leukocyte associated at this time, the best method to reduce CMV risk may be to effectively perform leukocyte reduction of blood from donors known to be CMV seropositive for at least 1 year.

Additional infectious risks include other types of hepatitis (A, B, E) and retroviruses (human T-cell lymphotropic virus types I and II and HIV-2), syphilis, parvovirus B19, Epstein-Barr virus, human herpesvirus 8, West Nile virus, yellow fever vaccine virus, malaria, babesiosis, Anaplasma phagocytophilum, and Chagas disease. Variant Creutzfeldt-Jacob disease has also been transmitted by blood transfusions in humans.

Transfusion-associated risks of a noninfectious nature that may occur include hemolytic and nonhemolytic transfusion reactions, fluid overload, graft versus host disease, electrolyte and acid-base imbalances, iron overload if repeated transfusions are needed long term, increased susceptibility to oxidant damage, exposure to plasticizers, hemolysis with T-antigen activation of red blood cells, post-transfusion purpura, acute lung injury, immunosuppression, and alloimmunization (see Table 468-1). Immunomodulation may be reduced by leukocyte reduction. Transfusion reactions and alloimmunization to red blood cell and leukocyte antigens seem to be uncommon in infants. Adverse effects are seen primarily in massive transfusion settings, such as exchange transfusions and trauma or surgery, in which relatively large quantities of blood are needed, but are rare with the small-volume transfusions usually given.

Premature infants are known to have immune dysfunction, but their relative risk of post-transfusion graft versus host disease is controversial. The postnatal age of the infant, the number of immunocompetent lymphocytes in the transfusion product, the degree of human leukocyte antigen compatibility between donor and recipient, and other poorly described phenomena determine which infants are truly at risk for graft versus host disease. Regardless, many centers caring for preterm infants transfuse exclusively γ-irradiated cellular products. Directed donations with blood drawn from blood relatives must always be irradiated because of the risk of engraftment with transfused HLA-homozygous, haploidentical lymphocytes. Cellular blood products given as intrauterine and exchange transfusions should be γ-irradiated, as are transfusions for patients with severe congenital immunodeficiency disorders (severe combined immunodeficiency syndrome and DiGeorge syndrome requiring heart surgery) and transfusions for recipients of hematopoietic progenitor cell transplants. Other groups who are potentially at risk but for whom no conclusive data are available include patients given T-cell antibody therapy (antithymocyte globulin or OKT3), those with organ allografts, those receiving immunosuppressive drug regimens, and those infected with HIV.

Current practice uses γ-irradiation from a cesium, cobalt, or linear acceleration source at doses ranging from 2,500 to 5,000 cGy; a minimum dose of 2,500 cGy is required. All cellular blood components should be irradiated, but frozen “acellular” products, such as plasma and cryoprecipitate, do not require it. Leukocyte reduction cannot be substituted for γ-irradiation to prevent graft versus host disease.