Transfusion Reactions

• Transfusion-related acute lung injury (TRALI) is characterized by the onset of hypoxemia and bilateral pulmonary edema within 6 hours of a transfusion, in the absence of other causes such as heart failure. It is attributed to donor plasma human leukocyte antigen class I and II antibodies activating recipient neutrophils, leading to a lung immune response. In 2006, US blood collection agencies instituted a male-only plasma donor policy because multiparous females are more likely to carry the offending antibodies. The TRALI rate decreased to about one-third of its previous level. TRALI is now the leading cause of transfusion-related mortality. Treatment of this noncardiogenic pulmonary edema is aggressive supportive care.

• Transfusion-associated circulatory overload (TACO) occurs in 1% to 6% of transfused patients and can cause pulmonary edema secondary to fluid overload. Large amounts of plasma transfused during MT or coagulopathy correction increase the likelihood of TACO.

• Transfusion-related immunomodulation (TRIM) is a risk with allogeneic red blood cell transfusion. Although incompletely understood, there is a decrease in immunity with an increased incidence of nosocomial infection, postoperative infection, and cancer recurrence.

• Febrile reactions occur in approximately 1% of all transfusions. In an awake patient, this is usually no more than an annoyance that requires antipyretics and decreasing the infusion rate. Leukoreduction decreases the likelihood of a febrile reaction.

• Allergic (nonanaphylactic/nonanaphylactoid) nonhemolytic reactions to properly crossmatched blood manifest as an increase in temperature, pruritus, and urticaria. This can be difficult to diagnose in the anesthetized patient. Treatment consists of the administration of antihistamines and discontinuation of the transfusion.

• Hemolytic reactions occur when incompatible blood is administered. The risk of an ABO- incompatible transfusion is 1:33,500 for red blood cell transfusion. Mortality remains high at approximately 40%. Caused by activation of the complement system, hemolytic reactions can be life threatening. In the awake patient, fever, chills, dyspnea, and substernal and lumbar pain are seen in addition to hypotension. Under general anesthesia, the only sign that is not masked is hypotension. Free hemoglobin detected in the plasma or urine is indicative of a transfusion reaction. Substances released by the hemolyzed cells can lead to disseminated intravascular coagulation (DIC) and acute renal failure (ARF). Treatment consists of immediate discontinuation of the transfusion. Hypotension should be treated with hydration, vasopressors, and inotropic agents if needed. Urinary output must be maintained by adequate hydration. Although its value is uncertain, sodium bicarbonate has been used to alkalinize the urine to improve the solubility of the hemoglobin degradation products.

• Other reactions include posttransfusion purpura, microchimerism, and graft-versus-host disease.

Transmission of Disease

• Human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, and cytomegalovirus can all be transmitted by transfusion of blood products. Because the risk of disease transmission increases with each unit of blood or its components given, they must be carefully scrutinized before being administered. Currently, the incidence of posttransfusion HIV 1 and 2 infection is 1:1,476,000 per transfused unit of blood, similar to the risk of hepatitis C transmission, which is 1:1,149,000 per unit transfused. In comparison, the risk of hepatitis B transmission is higher, approximately 1 per 350,000 units. Nevertheless, cytomegalovirus remains the most common viral agent transmitted by transfusion; it produces clinically important infections only in patients with immunosuppression. Laboratory testing done to detect these viruses includes enzyme immunoassays and nucleic acid testing.

• Malaria, syphilis, Lyme disease, Chagas disease, West Nile virus, Creutzfeldt-Jakob disease, and other diseases can also be transmitted through transfusion of blood.

• Bacterial infection occurs in 1:75,000 transfusions. As new nonhemoglobin solutions appear on the market, less blood will be transfused and disease transmission will diminish.

Microembolization

Microembolization can occur from the transfusion of blood or its components. Stored blood forms microaggregates that are too small to be removed by standard 170-µm blood filters. Smaller filters have been developed to remove these particles. When using blood filters in the 20- to 40-µm range, the rate of transfusion is dramatically decreased because of the increased resistance of the filters. Some early reports suggested that these microaggregates lead to pulmonary dysfunction, but this has never been proven.

References

• Blumberg N, Refaai MA, Heal JM. Transfusion-induced immunomodulation. In: Murphy MF, Roberts DJ, Yazer MH, Dunbar NM, eds. Practical Transfusion Medicine. 6th ed. Wiley-Blackwell; 2022:153-167.
• Chestnut DH, Wong CA, Tsen LC, et al, eds. Chestnut's Obstetric Anesthesia: Principles and Practice. 6th ed. Elsevier; 2020:920-921, 1291.
• Steurer MP, Sikorski RA, Richards JE, Galvagno SM. Anesthesia for trauma. In: Gropper MA, Cohen NH, Eriksson LI, Fleisher LA, Johnson-Akeju S, Leslie K, eds. Miller's Anesthesia. 10th ed. Elsevier; 2024:2000-2043.
• Virk MS, Pandey S, Andrews J. Transfusion medicine. In: Means RT, Arber DA, Glader BE, et al, eds. Wintrobe's Clinical Hematology. 15th ed. Wolters Kluwer; 2024:558-598.