Transfusion risks are typically categorized into infectious and noninfectious complications. Adverse events are reported to complicate approximately 10% of the 14.2 million red cell units administered annually in the United States. Fortunately, less than 0.5% of these are serious reactions. Nevertheless, death related to transfusion may be significantly underreported.1 Patient concerns regarding transfusion risks have traditionally focused on the spread of viral infectious diseases. However, 40% to 50% of deaths related to transfusion result from noninfectious complications and bacterial contamination of platelets.2 The leading causes of allogeneic blood transfusion-related mortality in the United States in the order of number of reported deaths are transfusion-related acute lung injury (TRALI), ABO and non-ABO hemolytic transfusion reactions (HTR), and transfusion-associated sepsis (TAS).3
Infectious Transfusion Risks
Improvements in screening strategies for prospective donors and testing of donated blood products have significantly reduced the likelihood of viral infection from contaminated blood. In the United States, each unit of donated blood is tested for hepatitis B surface antigen and core antibody, hepatitis C antibody, HIV and human T-cell leukemia virus (HTLV) types 1 and 2 antibodies, West Nile virus, and syphilis. Nucleic acid testing is also performed for HIV-1 and hepatitis C, as it detects viral genome before an antibody response develops. Table 2-1 outlines infectious risks from transfusion and their estimated frequency. Composite risk for HIV, hepatitis B and C, and HTLV infection from transfusion is estimated to be less than 1 in 30,000.
TABLE 2-1.Infectious Risks From Transfusion and Their Estimated Frequency4,5 ||Download (.pdf) TABLE 2-1. Infectious Risks From Transfusion and Their Estimated Frequency4,5
|Hepatitis B ||1 in 100,000-1 in 400,000 |
|Hepatitis C ||1 in 1.6 million-1 in 3.1 million |
|HIV 1 and 2 ||1 in 1.4 million-1 in 4.7 million |
|HTLV 1 and 2 ||1 in 500,000-1 in 3 million |
|Bacterial contamination PRBCs ||1 in 28,000-1 in 143,000 |
|Bacterial contamination platelets ||1 in 2000-1 in 8000 |
Other infectious diseases can be transmitted through blood products but are not universally screened by direct testing of the blood product. Rather, screening of the individual donor is performed by a detailed questionnaire designed to identify persons at risk for harboring specific diseases. Some examples of these diseases include cytomegalovirus, Chagas disease, babesiosis, malaria, Creutzfeldt-Jakob disease, hepatitis A, Lyme disease, Epstein-Barr virus, and human herpes viruses. Alarmingly, 1 to 2 per 100 donations test positive for hepatitis G virus, SEN virus, and transfusion-transmitted virus. The significance of these viruses remains to be determined.2
Clinically significant cytomegalovirus (CMV) infections usually occur in immunocompromised patients. However, a small but significant portion of persons in the population has never been exposed to CMV and has no natural immunity to it. Although CMV infection in the adult is usually a benign, subclinical process, primary maternal infection confers a 40% risk of in utero transmission and can have devastating effects. Therefore, CMV seronegative, leukoreduced blood products should be administered to the seronegative pregnant patient.
Bacterial contamination of blood products, particularly platelets, accounts for 17% to 22% of infectious deaths related to transfusion, making this one of the leading causes.6
Noninfectious Transfusion Risks
Noninfectious transfusion risks are more common than infectious risks and are often underrecognized and underreported. Noninfectious risks of transfusion can be further categorized as hemolytic and nonhemolytic in nature.
Hemolytic Transfusion Reactions
Acute Hemolytic Transfusion Reaction
Over 250 red cell antigens have been identified, any of which can lead to a hemolytic transfusion reaction when administered to incompatible recipients. Testing of blood type, antibody screen, and crossmatch is performed to avoid transfusion of incompatible blood. Approximately 0.2% to 0.6% of the general population is sensitized.1 Acute hemolytic reactions occur with exposure to incompatible ABO types at a rate of 1 in 12,000 to 19,000 units transfused. Clinically, the patient develops sudden onset of fever, chills, flank and back pain, circulatory collapse, and microangiopathic thromboses. This type of reaction is most commonly the result of error.
Delayed Hemolytic Transfusion Reaction
Delayed hemolytic reactions occur as a result of exposure to incompatible human leukocyte antigen (HLA) and complicate 1 in 1000 to 9000 red cell transfusions.7 HLAs are present on all cells except mature red blood cells. HLA alloimmunization occurs in response to a prior exposure to incompatible blood or from prior pregnancy. Because these antigens are present on tissues apart from red cells, the hemolytic reaction occurs extravascularly and is less severe than reactions to incompatible red cell antigens.
Nonhemolytic Transfusion Reactions
The nonhemolytic transfusion reaction is much more common (1 in 100). Usually characterized by febrile or urticarial reactions, more serious reactions such as transfusion-related lung injury and graft-versus-host disease can also develop.
Transfusion-Related Acute Lung Injury
Transfusion-related acute lung injury (TRALI) is defined as acute lung injury which develops within 6 hours of transfusion, in the absence of left atrial hypertension or other risk factors for acute lung injury (ie, pneumonia, sepsis, aspiration, fractures, and pancreatitis).8 TRALI complicates at least 1 in 5000 transfusions with a 6% risk of mortality and is believed to be the most common cause of mortality related to transfusion.9 Clinically, patients develop sudden onset of respiratory distress, pulmonary edema, fever, and hypotension. The etiology is unclear; however, the “two-hit” hypothesis for the pathogenesis of TRALI proposes neutrophil sequestration and priming in the recipient followed by activation of recipient neutrophils by a factor in the blood product.10 Female gender and increased parity of the donor are associated with an increased risk of TRALI. A multicenter cohort study showed that plasma or whole blood from female donors was one of the 3 major blood component risk factors for TRALI.11 If TRALI is suspected, the transfusion should be immediately discontinued and reported to the blood bank. Treatment is primarily supportive and may require ventilatory support. Unlike acute respiratory distress syndrome (ARDS), TRALI typically resolves rapidly and is less likely to be fatal. It is important to consider TRALI in the differential diagnosis of acute pulmonary edema and avoid use of diuretics, as it may worsen outcome.12,13 Prevention of TRALI involves deferring donors implicated in a case of TRALI and restricting transfusion of plasma products from multiparous women which are most likely to contain antileukocyte antibodies.8
Fever associated with the administration of leukoreduced blood products occurs in 0.1% to 1% people annually and is more common if the product is not leukoreduced.14 The febrile response is hypothesized to be the result of cytokine release from white blood cells in the blood product. Utilization of leukoreduced blood products and prophylactic antipyretic therapy dramatically decreases the likelihood of a febrile reaction.1
Allergic reactions manifest primarily as urticaria, itching, flushing, rash, or angioedema without fever. These types of responses are common and can be quite severe, including anaphylaxis. Antihistamines can be administered prophylactically. With minor reactions, intravenous antihistamines may allow completion of the transfusion. More severe reactions require cessation of the transfusion.
Alloimmunization can result in platelet antibodies which may prevent therapeutic response in the thrombocytopenic patient who receives platelet transfusion. Rarely, graft-versus-host disease can occur following transfusion of some blood components (platelets, white blood cells, etc) into an immunocompromised individual.
Transfusion-Associated Graft-Versus-Host Disease
This rare complication of transfusion primarily affects immunosuppressed individuals and carries a high mortality rate (>90%). Irradiation of blood products may eliminate this risk.14
Massive transfusion, defined as replacement of an entire blood volume in 24 hours or administration of more than 10 units in a few hours, carries particular risks to the patient. The citrate component in stored blood products binds with calcium and this leads to hypocalcemia when administered in large amounts. Alkalosis is also common following massive transfusion, as is hypothermia, potassium disturbances, and decreased 2,3-DPG. Prewarming the infused blood and maintaining normothermia of the patient can minimize some of these effects. Monitoring acid-base balance as well as potassium and calcium levels is essential in the setting of massive transfusion. Coagulation defects are also common when patients receive large amounts of blood products; therefore, monitoring and correction of clotting status are warranted.
The transfusion of blood products does appear to suppress the host immune system with both beneficial and detrimental effects. Patients receiving transfusions have lower rates of renal transplant rejection and improvement in certain autoimmune disease activity, that is, rheumatoid arthritis.1 However, more recent studies suggest that patients, particularly surgical and trauma patients, receiving blood transfusions have increased rates of mortality, postoperative infections, and multiorgan system failure.2,4,15,16 This has prompted an ongoing reevaluation of the thresholds for transfusion in critically ill and surgical patients.