Blood and Blood Products : Transfusion Reactions and Complications

Acute Reactions

Allogeneic blood transfusion (ABT) reactions may be categorized as acute versus delayed and immune mediated versus non–immune mediated. Specific diagnostic and management strategies will be discussed, as well as strategies to reduce transfusion-related morbidity and mortality ( Table 101.2 ).

Acute Hemolytic Transfusion Reactions

Acute hemolytic transfusion reactions (AHTRs) are life-threatening reactions caused by acute intravascular hemolysis resulting from the binding of donor red cell antigens with recipient antibodies to form immune complexes. These reactions are often caused by clerical error (incorrect blood component transfused). These Ag-Ab immune complexes cause complement fixation, leukocyte activation, intravascular hemolysis, and hemoglobinuria and induce the formation of cytokines, resulting in hemodynamic instability, flank pain, fever, chills, and disseminated intravascular coagulation (DIC). Severe reactions are usually the result of ABO incompatibility or possibly to other red blood cell (RBC) Abs from prior alloimmunization. The severity of the reaction depends on the recipient Ab titer, the volume transfused, and the rate of transfusion. Most fatalities have been associated with transfusions greater than 200 mL, and for transfusions greater than 1000 mL, the mortality rate approaches 44%. Improved administrative systems have reduced the number of ABO-incompatible AHTRs, with the Food and Drug Administration (FDA) reporting 131 ABO-incompatible AHTR fatalities in 1976 to 1985 compared with 13 in 2010 to 2014. Laboratory findings include hemoglobinemia, hemoglobinuria, positive direct Ab test (DAT), and findings of DIC (prolonged prothrombin time/partial thromboplastin time, thrombocytopenia, hypofibrinogenemia). Despite the presence of more than 250 RBC antigens, AHTRs are usually the result of ABO or RH D group incompatibility.

Febrile Nonhemolytic Transfusion Reactions

Febrile nonhemolytic transfusion reactions (FNTRs) are common reactions characterized by fever and may be associated with chills, rigors, and malaise occurring during a transfusion or a few hours after a transfusion. They are usually caused by recipient antibodies reacting to donor leukocyte antigens to form an antigen-antibody complex with the release of complement-mediated endogenous pyrogens (interleukin-1 [IL-1], IL-6, and tumor necrosis factor–alpha). Management is usually symptomatic with antipyretics, but FNTRs are a diagnosis of exclusion because febrile reactions may also accompany more serious reactions such as AHTR, transfusion-related acute lung injury, and sepsis. In most circumstances the transfusion rate can be decreased without abandoning the transfusion. In countries where universal leukoreduction has been implemented, there has been a reduction in FNTRs.

Allergic Reactions

Allergic reactions are common, are usually mild, and present with urticaria, pruritus, and possibly fever. The majority are caused by an antibody-antigen reaction to serum proteins present in donor plasma and are immunoglobulin E (IgE) mediated. The presence of an urticarial transfusion reaction (UTR) does not necessitate abandoning the transfusion. The transfusion should be stopped, antihistamines should be administered, and the transfusion may be resumed when the symptoms have diminished.

Anaphylactic transfusion reactions are rare, but serious reactions are often found in patients that have a hereditary immunoglobulin A (IgA) deficiency and have anti-IgA antibodies to IgA in the transfused product or antibodies to other donor plasma constituents. This anti-IgA IgA immune complex interaction occurs immediately and is not dose related. In addition to the urticaria, present in UTRs, clinical features include angioedema, bronchospasm, and hypotension. Management is the same as for other causes of anaphylaxis and includes fluid resuscitation, epinephrine, antihistamines, and corticosteroids, depending on the severity of the reaction.

Transfusion-Related Acute Lung Injury ( Box 101.1 )

Transfusion-related acute lung injury (TRALI) is considered to be one of the leading causes of transfusion-related morbidity and mortality in developed countries. It presents as an acute respiratory distress syndrome within 6 hours of transfusion. Its incidence varies significantly from country to country and has been most likely underestimated due to a lack of a consensus definition before 2004. The fact that it is a clinical diagnosis of exclusion and the differing methods of reporting (active vs. passive hemovigilance) have been the main factors for its underestimation. Recent reviews have noted an incidence of up to 1.12% per unit of blood transfused, with an incidence of 8% per transfused high-risk recipient, corresponding to an increase in reporting. TRALI refers to the new onset of acute lung injury (ALI) within 6 hours of completion of a transfusion where there are no other risk factors for ALI and no other signs of acute pulmonary vascular overload. Clinical features include hypoxemia, dyspnea, cyanosis, and tachycardia and may be accompanied by fever and hypotension. It is important to differentiate TRALI from other forms of ALI, including circulatory overload (TACO; see later in this chapter) and myocardial or valvular heart disease. The acute hypoxemia is defined by a Pa o ₂ /F _i o ₂ ratio less than 300 mm Hg associated with chest radiographic findings of bilateral pulmonary infiltrates without signs of cardiogenic pulmonary edema. Because patients with coexisting pulmonary disease who receive an ABT would be excluded from the diagnosis of TRALI, the Canadian consensus group in 2004 included the definition of “possible TRALI” in patients who have one or more risk factors for ALI who develop worsening ALI after a transfusion. In this high-risk population, the development of “delayed TRALI” has also been described up to 72 hours after transfusion and is associated with a high mortality rate.