Transfusion Reactions Clinical Presentation

Updated: Jan 12, 2021
  • Author: S Gerald Sandler, MD, FCAP, FACP; Chief Editor: Emmanuel C Besa, MD  more...
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A history of previous blood transfusions or pregnancy is often present but is not essential for the diagnosis of a febrile nonhemolytic transfusion. Acute transfusion reactions caused by ABO antibodies, transfusion-related acute lung injury (TRALI; from donor's antibodies), allergy, IgA/anti-IgA anaphylaxis, or sepsis may occur during the first transfusion or subsequent transfusions.

Persons known to have formed red cell alloantibodies as the result of previous transfusions or pregnancy should be informed and provided with a written report listing the antibodies to be presented to the transfusion service if additional transfusions are required at another hospital.

Red cell antibodies may decrease in titer and, although remaining clinically important, may not be detected by routine compatibility testing before future red cell transfusions. Ask patients scheduled for red cell transfusions about any history of previous transfusions and if they are aware of any complications or blood bank antibody problems. Obtain details of any previous transfusions during the medical history or when obtaining the patient's informed consent for a transfusion.

In individuals with sickle cell disease, clinical manifestations of delayed hemolytic transfusion reactions (DHTRs) usually appear 5–15 days after the triggering transfusion, and include hemoglobinuria, jaundice, and pallor due to acute hemolysis. In addition, patients may have signs and symptoms that mimic severe vaso-occlusive crisis (ie, pain, fever, and acute chest syndrome), as well as profound anemia, often with reticulocytopenia. If DHTR is misdiagnosed as vaso-occluisive crisis and the patient is treated with an additional transfusion, this may further exacerbate hemolysis and clinical symptoms and cause life-threatening multiorgan failure. [5, 6]



Acute hemolytic reactions manifest as follows:

  • Early signs may include fever, hypotension, flushing, wheezing, anxiety, and/or red-colored urine
  • Late signs may include a generalized bleeding tendency (DIC) and/or hypotension

Nonhemolytic febrile reactions typically involve only fever. However, some patients also have severe rigors, shaking, chills, hypotension, and vomiting.

Allergic reactions typically comprise maculopapular rash and/or urticaria without fever or hypotension. Anaphylactic reactions manifest as follows:

  • Dyspnea
  • Wheezing
  • Anxiety
  • Hypotension without fever
  • Bronchospasm in severe cases

Transfusion-related acute lung injury (TRALI) manifests as rapid onset of shortness of breath, hypoxemia, and rales, without signs of acute cardiogenic pulmonary edema and fever.

Circulatory (volume) overload manifests as follows:

  • Shortness of breath
  • Rales
  • Orthopnea
  • Tachycardia
  • Distended jugular veins
  • Other evidence of cardiac decompensation

Continuous monitoring of vital signs during general anesthesia may prevent acute circulatory (volume) overload, but it may not detect early signs of other reactions (eg, acute hemolytic transfusion reactions). However, the onset of abnormal bleeding/generalized oozing during surgery in a transfused patient should raise the question of a hemolytic transfusion reaction with disseminated intravsacular coagulation (DIC).

Bacterial contamination manifests as high fever, shock, tachycardia, and weak pulse, without a clear focus of infection. Examination of the contents of the container of blood being transfused may reveal clots, discoloration, or a difference in color between the contents of the bag (hemolyzed by contaminating bacteria) and the contents of the segmented tubing attached to the bag (not hemolyzed, no bacteria). In a review of septic transfusion reactions resulting from bacterially contaminated platelets, Hong et al reported that the reactions developed 9 to 24 hours posttransfusion, and occurred only in neutropenic patients. [54]



Acute hemolytic reactions (ABO incompatibility)

Accidental transfusion of RBCs of a different ABO type than the patient's typically occurs for one of two reasons, as follows:

  • Misidentification of either the patient or the blood component when the blood sample was collected for compatibility testing

  • Failure to recognize that two patients have the same or similar names but different ABO blood types

Most transfusions of incorrect RBCs to the incorrect patient due to misidentification are clinically benign. More than 60% of random units of RBCs in a blood bank are serologically compatible with random recipients because approximately 40% are type O (ie, universal donor) and 20% are the same blood type as the patient or are otherwise ABO-compatible.

Febrile nonhemolytic reactions

Cytokines and other normal constituents of leukocytes, platelets, or plasma accumulate in blood components during storage. When blood components are transfused, some recipients react with varying generalized symptoms, of which fever is the most common symptom.

Allergic reactions

The clinical presentation of rash, pruritus, and/or urticaria during a transfusion suggests that the recipient was exposed to a foreign substance in the blood product to which the recipient is sensitized. Usually, a specific allergen is not identified. Studies in the medical literature suggest that causes of allergic reactions include polymorphic proteins in the donors' plasma, food (eg, nuts, tomatoes), or medications (eg, penicillin) that the donor ingested immediately before collection of the implicated blood product.

Anaphylactic reactions

Most cases of anaphylaxis are reported in recipients with IgA deficiency who developed anti-IgA and whose transfused product contains donor plasma with a normal content of IgA. Not all IgA-deficient persons who have anti-IgA have a history of transfusions or pregnancy. Similar reactions in ahaptoglobinemia have been reported.

Transfusion-related acute lung injury

Neutrophils are the effector cells that adhere to the pulmonary endothelium to increase permeability and cause pulmonary edema. Elements leading to activation of the neutrophils include transfused human leukocyte or neutrophil antigen (HLA or HNA) antibodies and transfused bioactive substances such as lipids or cytokines. Patients with certain clinical conditions (eg, infection, inflammation, surgery) have primed neutrophils that are susceptible to activation by transfused bioactive substances.

Because pregnancy is a common cause of alloimmunization to HLAs and HNAs, most cases of TRALI have been traced to plasma-containing blood components collected from female blood donors. [55] When the American Red Cross converted to predominantly male-donated plasma, the number of cases of TRALI decreased very significantly from 2006 to 2008. [55]

Circulatory (volume) overload

Increased fluid volume in susceptible patients, including those with cardiovascular compromise, elderly patients, and small children, may result in pulmonary edema. A usual transfusion rate is 2-2.5 mL/kg per hour. In at-risk patients, blood products can be transfused at a slower rate.

Bacterial contamination (sepsis)

Bacteria may enter the blood product container if it is opened at any time from collection from the donor until transfusion to the recipient. Bacteria on the donor's skin may enter the container if the needle entry site on the donor's skin is sterilized incompletely.

Some donors implicated in septic reactions have low concentrations of bacteria (eg, Yersinia enterocolitica) in their blood (eg, bacteremia) but do not have a fever or other signs at the time of collection. If such contaminated blood is stored for a few days at room temperature (eg, platelets) or for a few weeks at refrigerated temperature (eg, red cells), bacteria may grow and elaborate endotoxin, which is a major adverse factor in such reactions. [56]