Reference Work Entry

Encyclopedia of Molecular Mechanisms of Disease

pp 2097-2098

Transfusion Reactions

  • Karina YazdanbakhshAffiliated withLaboratory of Complement Biology, New York Blood Center
  • , Millicent SuttonAffiliated withLaboratory of Complement Biology, New York Blood Center


Acute hemolytic transfusion reactions; Delayed transfusion reactions; Febrile non-hemolytic transfusion reactions; Transfusion associated circulatory overload; TACO; Transfusion related acute lung injury; TRALI

Definition and Characteristics

A transfusion reaction is an adverse event which occurs during or after the transfusion of a blood product [1,2]. In hemolytic transfusion reactions (HTRs), transfused donor red blood cells (RBCs) are destroyed by the host’s immune system and they can be acute (immediate) or delayed, and severe or mild. In severe acute hemolytic transfusion reactions (AHTRs), RBCs are destroyed intravascularly as seen with ABO-incompatible transfusion reactions and disseminated intravascular coagulation (DIC) and renal failure can also occur. In delayed transfusion reactions (DHTRs), RBCs are destroyed extravascularly, rarely causing hemoglobinemia and hemoglobinuria. Febrile non-hemolytic transfusion reactions (FNHTRs) are caused by antibodies in the transfusion recipient to white cells present in the donor blood or component. Transfusion associated circulatory overload (TACO) results from a rapid or massive transfusion of blood. Transfusion related acute lung injury (TRALI) is characterized by acute respiratory distress resulting from transfusion of blood components. Another possible type of transfusion reaction is an allergic reaction to the transfused plasma products.


AHTRs and DHTRs occur as frequently as one per 1,500 units transfused. The mortality rate is estimated at one per 100,000 units transfused which is mostly due to transfusion of ABO incompatible blood, the major cause of which is due to clerical errors in issuing the wrong unit [3]. TRALI is the most common cause of fatal transfusion reactions with a mortality rate of one in 5,000 transfusions.


No genes are known to affect transfusion reactions.

Molecular and Systemic Pathophysiology

Factors influencing the severity of a HTR include: the class and the subclass of the antibody causing the reaction, the specifically, titer and avidity and its ability to activate the complement system; the number and density of the target RBC antigen that the antibody reacts with and the amount of incompatible red cells transfused [4]. If complement activation goes to completion, direct cell lysis can occur as seen in intravascular hemolysis, releasing complement split products C3a, responsible for the hypotension and tachycardia and C5a which can induce the activation of granulocytes and neutrophils. Intravascular hemolysis with excessive production of plasma free hemoglobin production competes with nitric oxide, a potent vasodilator resulting in renal ischemia and renal failure. In DHTR, RBCs are sensitized by antibodies and possibly complement factor C3 and are subsequently removed by macrophages in spleen and liver by phagocytosis. Release of endogenous pyrogens induced by antibodies to donor leukocytes or platelets occur in non hemolytic reactions, while immune mediated proinflammatory cytokine responses produced by activated macrophages are responsible for fevers associated with HTRs. Passive transfer of donor antibodies directed against recipient human leukocyte (HLA) antigens has been implicated in TRALI.

Diagnostic Principles

Laboratory tests to determine presence of hemolysis include: reticulocyte count, serum haptoglobin, LDH and bilirubin levels and examination of the peripheral smear. A direct antiglobulin test, DAT, should be performed to detect donor RBC sensitization. A newly positive DAT in the absence of hemoglobinemia and hemoglobinuria is consistent with DHTRs occurring typically 10–14 days after a transfusion. Elution off the RBCs can elucidate the identification and specificity of the antibodies. Acute intravascular hemolysis is generally evident within minutes. Fever involving increase in body temperature of >1oC with chills are the most common features of AHTR and DHTR. Allergic reactions to plasma products are usually mild but can be severe manifesting as hives, wheezing, hypotension or shock. Shortness of breath, dyspnea, pulmonary edema and increased systolic blood pressure are symptoms of TACO which can result in deterioration of cardiovascular status in some recipients who are already compromised. TRALI is defined as acute onset pulmonary edema, in the absence of cardiogenic components, occurring within 1–6 h of transfusion and in many cases symptoms resolves within 24–48 h. Testing of the donor for HLA or granulocyte antibodies and demonstration of the specificity against recipient antigen may be helpful in the diagnosis.

Therapeutic Principles

Careful monitoring of the recipient’s renal and coagulation status and rigorous diuresis to maintain adequate urinary output is the mainstay of therapy of intravascular hemolysis. DIC and shock should be treated if present. FNHTRs are typically mild and are managed with antipyretics administered prior to transfusion and can be prevented with the use of leuko-reduced products. Antihistamines are administered for mild non-systemic allergic reactions to plasma proteins however corticosteroids may be required for more severe reactions. If bacterial contamination is suspected, the recipient should be cultured and prompt administration of broad spectrum antibiotic should be initiated. All components from that donor should be cultured and quarantined to prevent the possibility of subsequent recipients being affected. Management of TACO is supportive. Symptoms generally resolve when the transfusion is stopped. Phlebotomy is rarely used however diuretics may be warranted in particular situations. There is no specific therapy for TRALI. Care is supportive and diuresis may not be beneficial.

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© Springer-Verlag GmbH Berlin Heidelberg 2009
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