Transfusion Reactions in Emergency Medicine 

Patients with acute blood loss or symptomatic anemia frequently require blood replacement therapy in the emergency department (ED). Although blood replacement therapy is generally safe, it should be understood that certain risks accompany the transfusion of blood and plasma components. Accordingly, emergency physicians must be familiar with and be able to manage adverse transfusion reactions, ranging from self-limited febrile responses to life-threatening intravascular hemolysis.

Hemolytic transfusion reactions

Hemolytic transfusion reactions are the result of antibodies in the recipient's plasma directed against antigens on the donor's erythrocytes. This results in rapid intravascular hemolysis of the donor red blood cells. ABO incompatibility due to clerical error is the most frequent cause. This results in hemoglobinemia, hemoglobinuria, disseminated intravascular coagulation (DIC), renal failure, and complement-mediated cardiovascular collapse.

The recipient's antibodies to Rh or non-ABO antigens cause extravascular hemolytic reactions. These patients usually have been exposed to the antigen through previous pregnancies, transplantation, or transfusions. Antibody titers often are too low to be detected through routine antibody screening, but production of antibodies becomes amplified with reexposure. These antibodies do not activate complement; therefore, no intravascular hemolysis occurs. Instead, the RBCs are tagged for removal by splenic macrophages.

Nonhemolytic febrile reactions

Nonhemolytic febrile reactions are thought to stem from the formation of cytokines during the storage of the blood. These reactions seldom proceed to hypotension or respiratory distress.

Anaphylactic reactions

Anaphylactic reactions most often are observed in those patients with a hereditary immunoglobulin A (IgA) deficiency. Some of these patients have developed complement-binding anti-IgA antibodies that cause anaphylaxis when exposed to donor IgA.

Proteins in the donor plasma can cause minor allergic reactions. This is an anaphylactoid reaction and is observed more frequently with components containing large amounts of plasma, such as whole blood, pooled platelets, and fresh frozen plasma.

Acquired diseases

Infectious diseases also may be transmitted through transfusion.

Graft-versus-host disease

Graft-versus-host (GVH) disease occurs when donor lymphocytes mount an immune response against the recipient's lymphoid tissue. Normally, the donor lymphocytes are recognized as being foreign and are destroyed. In situations when the donor is immunocompromised or when the donor is homozygous and the recipient is heterozygous for an HLA haplotype, these normal defense mechanisms may fail, resulting in GVH disease.

Transfusion-related acute lung injury

Transfusion-related acute lung injury may be caused by transfusing any plasma-containing blood product. It is caused by the interaction between the recipient's leukocytes and preexisting donor antileukocyte antibodies. This results in complement activation and increased pulmonary vascular permeability. In addition, mediators of inflammation that form while the blood is in storage are also felt to be contributory.^[1]

Massive transfusion complications

Massive transfusion is defined as the replacement of more than one-half of the blood volume within a 24-hour period or the replacement of 10 units of blood over the course of a few hours. Complications of massive transfusion include the following:

• Coagulopathy is caused by a dilutional effect on the host's clotting factors and platelets, as well as the lack of platelets and clotting factors in packed red blood cells.
• Volume overload
• Hypothermia
• Hyperkalemia may be caused by lysis of stored red cells and is increased in irradiated red blood cells.
• Metabolic alkalosis and hypokalemia may be caused by the transfusion of a large amount of citrated cells.
• Hypocalcemia due to citrate toxicity may occur in those with hepatic failure, congestive heart failure (CHF), or other low-output states. It is increasingly uncommon with the use of component therapy.

Frequency

United States

• Hemolytic transfusion reactions occur in 1 per 40,000 transfused units of packed RBCs.
• Nonhemolytic febrile reactions and minor allergic reactions are the most common transfusion reactions, each occurring in 3-4% of all transfusions.
• Nonhemolytic febrile reactions and extravascular hemolysis are observed more commonly in patients who have developed antibodies from prior transfusions.
• Anaphylactic reactions occur in 1 per 20,000 transfused units.
• Due to improved preventative measures, the incidence of GVH disease is less than 0.15%
• Transfusion-related acute lung injury complicates 0.1-0.2% of all transfusions.
• Risk of transfusion-related hepatitis B is 1 per 50,000 units transfused. Risk for hepatitis C is 1 per 3000-4000 units transfused.
• Risk of transfusion-related HIV infection is 1 per 150,000 units transfused.

Mortality/Morbidity

Hemolytic transfusion reactions result in death in 1 per 100,000 units transfused.

• Transfusion-related hepatitis C causes chronic hepatitis and occurs in 50% of infected recipients.
• Cirrhosis develops in 10% of those with hepatitis.
• Transfusion-associated GVH disease is associated with an 80-90% mortality rate.
• The mortality rate of transfusion-related acute lung injury is 5%.

Sex

Nonhemolytic febrile reactions and extravascular hemolytic reactions are more common in parous females.

Age

Children have a greater risk of developing transfusion-related HIV than adults.