Chapter 46
Transfusion Reactions
Both mild and serious transfusion reactions can occur even when procedures are followed appropriately. Such reactions to blood products occur with a predictable frequency (Table 46.1). Additional laboratory testing by the blood bank is often required to determine the etiology of the suspected transfusion reaction, the specifics of which take into account the type of blood product transfused. For example, TRALI can occur with any plasma-containing product (fresh frozen plasma [FFP], units of packed red blood cells [RBCs], and platelet concentrates), whereas AHTRs occur most frequently with RBC products.
TABLE 46.1
Frequencies of Acute Transfusion Reactions
Type of Reaction | Estimated Frequency (per Transfused Unit) |
Mild allergic reaction | 1/33–1/100 |
Febrile transfusion reaction | 1/100–1/200 |
Volume overload | 1/100–10,000 |
Transfusion-related acute lung injury (TRALI) | 1/5000‡ |
Acute hemolytic transfusion reaction (symptomatic) | 1/12,000–1/33,000 |
Anaphylactic reaction Septic reaction | 1/20,000–1/50,000 1/50,000∗ |
Nonimmune hemolysis | Unknown† |
∗Apheresis platelet units that have been tested for bacteria by culture.
†Although the actual incidence of nonimmune hemolysis is not well documented, it appears to be rare.
‡Milder forms may not be rare but are likely to go unrecognized.
In the context of transfusion reactions, this chapter only considers those that are acute. Indications for transfusions are discussed elsewhere (see Chapter 19). Also discussed elsewhere are acute reactions of particular concern with massive transfusion, including hypocalcemia and other electrolyte and metabolic disorders (see Chapter 39) and hypothermia (see Chapter 55).
Definitions and Pathophysiologic Mechanisms
Acute Hemolytic Transfusion Reactions (AHTR)
Approximately 23% of transfusion fatalities reported to the FDA are due to acute hemolysis of RBCs (i.e., AHTRs). AHTRs occur when antibodies against RBC antigens strongly fix complement and produce brisk intravascular hemolysis. The activation of complement triggers the coagulation cascade and elevated bradykinin. Brisk hemolysis also leads to the formation of RBC membrane fragments (stroma) and tissue factor. Together, these responses can lead to hypotension, renal failure, disseminated intravascular coagulation (DIC), and bleeding. Hypotension occurs from elevated bradykinin and tumor necrosis factor alpha (TNF-α). Renal failure may occur because of reactive renal splanchnic vasoconstriction after bradykinin release and acute renal tubular necrosis from toxicity of the RBC stroma. Historically it was thought that AHTRs resulted from clerical errors leading to the transfusion and subsequent destruction of ABO-incompatible blood by recipient IgM anti-carbohydrate antibodies. However, FDA data indicate that fatal AHTRs can also be caused by certain complement-fixing IgG antibodies directed against protein antigens on the RBC surface, such as those in the Kidd blood group system.
Allergic and Anaphylactic Reactions
Allergic reactions occur in 1% to 3% of transfusions. Anaphylaxis occurs with 1 in 20,000-50,000 transfusions. These reactions occur when antibodies exist against soluble plasma proteins introduced by any plasma-containing blood product. The actual protein antigen that causes the reaction is generally not identified and this type of reaction is often idiosyncratic, specific to a particular donor/recipient pair who are unlikely to cross paths again. The one notable exception is when plasma containing IgA antibodies serves as the allergen, upon transfusion into an IgA-deficient patient. In the most severe cases, anaphylaxis can occur when the recipient has high titer IgE antibodies against IgA. Fortunately, most IgA-deficient recipients are incompletely deficient in IgA and thus are not at risk for anaphylaxis. Mild reactions are generally limited to urticaria.