Introduction

Transfusion reactions are defined as adverse events associated with the transfusion of whole
blood or one of its components. These may range in severity from minor to life-threatening.
Reactions can occur during the transfusion (acute transfusion reactions) or days to weeks later
(delayed transfusion reactions) and may be immunologic or non-immunologic. A reaction may
be difficult to diagnose as it can present with non-specific, often overlapping symptoms. The
most common signs and symptoms include fever, chills, urticaria (hives), and itching. Some
symptoms resolve with little or no treatment. However, respiratory distress, high fever,
hypotension (low blood pressure), and red urine (hemoglobinuria) can indicate a more serious
reaction.
Types of transfusion reactions include the following: acute hemolytic, delayed hemolytic, febrile
non-hemolytic, anaphylactic, simple allergic, septic (bacterial contamination), transfusion-related
acute lung injury (TRALI), and transfusion-associated circulatory overload (TACO). All
suspected reactions should result in immediately stopping the transfusion and notifying the blood
bank and treating clinician.[1][2][3]
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Etiology
Immune-mediated transfusion reactions typically occur due to mismatch or incompatibility of the
transfused product and the recipient. They include naturally occurring antibodies in the
blood recipient (such as anti-A, anti-B which are typically responsible for acute hemolytic
transfusion reactions) as well as antibodies made in response to foreign antigens (alloantibodies).
These alloantibodies account for many reactions including mild allergic, febrile non-hemolytic,
acute hemolytic and anaphylactic. Antibodies present in the blood donor can also cause reactions
and are thought to be involved in transfusion-associated lung injury (TRALI).[4][5][6]
Non-immunologic reactions are usually caused by the physical effects of blood components or
the transmission of disease. Bacterial contamination, for example, results in septic transfusion
reactions and is caused by bacterial and/or endotoxin contamination of a blood product. This
may happen at the time of collection due to inadequate blood donor arm disinfection, the
presence of bacteria in the donor’s circulation at the time of collection, or due to improper
product handling after collection.
Transfusion reactions can also occur unrelated to factors intrinsic to the blood. Examples of these
include transfusion-associated volume overload (TACO) and hypothermia.
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Epidemiology
Transfusion reactions range in frequency from relatively common, (mild allergic and febrile non-
hemolytic reactions) to rare (anaphylaxis, acute hemolytic, and sepsis). Fatal adverse events have
been reported to occur most commonly with TRALI, and long-term or later adverse events are
typically the result of disease transmission.
The severity and incidence vary depending on the type of transfusion reaction, the prevalence of
disease in the donor population, and the extent of follow-up care the patient receives. Due to
advances in donor screening, improved testing, and automated data systems, the risks and
fatalities associated with the transfusion of blood products continue to decrease.[7][8]
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Pathophysiology
The pathophysiology varies based on the transfusion reaction.[9][10][11]
Acute Transfusion Reactions
 Mild allergic: Attributed to hypersensitivity to a foreign protein in the donor product.
 Anaphylactic: Similar to a mild allergic reaction, however resulting in a more severe
reaction. Sometimes this can occur in a patient with IgA deficiency who makes
alloantibodies against IgA and then receives blood products containing IgA.
 Febrile non-hemolytic: Generally thought to be caused by cytokines released from blood
donor leukocytes (white blood cells).
 Septic: Caused by bacteria or bacterial byproducts (such as endotoxin) which may
contaminate blood.
 Acute hemolytic transfusion reactions: Can result in intravascular or extravascular
hemolysis, depending on the specific etiology (cause). Immune-mediated reactions are
often a result of recipient antibodies present to blood donor antigens. Non-immune
reactions are possible, and occur when red blood cells are damaged before transfusion
(e.g., by heat or incorrect osmotic conditions).
 Transfusion-associated circulatory overload (TACO): Occurs when the volume of the
transfused component causes hypervolemia (volume overload).
 Transfusion-related acute lung injury: Acute lung injury is due to antibodies in the donor
product (human leukocyte antigen or human neutrophil antigen) reacting with antigens in
the recipient. The recipient’s immune system responds and causes the release of
mediators that lead to pulmonary edema. Possibly contributing to this are clinical
conditions that predispose the patient including infection, recent surgery, or
inflammation.
Delayed Transfusion Reactions
 Delayed hemolytic transfusion reaction: Typically caused by an anamnestic response to a
foreign antigen that the patient was previously exposed to (generally by prior transfusion
or pregnancy).
 Transfusion-associated graft-versus-host disease: Results from engraftment of donor
lymphocytes (commonly found in cellular blood products) into an immunocompromised
recipient’s bone marrow. The donor lymphocytes recognize the patient as foreign and
 react against the recipient’s body. The patient’s immune system is unable to clear the
foreign lymphocytes. This is rare but often fatal.
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History and Physical

A thorough understanding of the patient’s medical history and state of health is needed before
the transfusion is started. Vital signs are monitored and typically recorded at 15-minute intervals.
A small amount of change in vital signs during transfusion may be considered “normal.”  These
changes may include the following: plus or minus 0.5 C in temperature, plus or minus 5
respirations per minute, plus or minus 10 beats per minute in heart rate, and plus or minus 20 mm
Hg in blood pressure.  It is important to note that changes greater than these parameters do not
mean that there is a transfusion reaction, it suggests that the bedside nurse should be extra
vigilant in monitoring for a reaction. Abnormal responses include hives, itching, fever greater
than 1 C above the temperature at the start of transfusion, chills, hypotension, and dyspnea.
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Evaluation
Diagnosis of acute transfusion reactions begins by recognition of the signs and symptoms by the
bedside. Common signs and symptoms and differential diagnosis are listed below.[12][13][14]
 Urticaria/Itching
Urticaria (hives) and/or itching can be the presenting sign of a mild allergic reaction, but can also
be associated with the onset of a life-threatening anaphylactic reaction. The transfusion should be
stopped, and the patient should be carefully monitored for progression of symptoms.
 Fever/Chills
Fever and/or chills are most commonly associated with a febrile, non-hemolytic reaction,
however; they can also be the first sign of a more serious acute hemolytic reaction, TRALI, or
septic transfusion reaction. If the temperature rises 1 C or higher from the temperature at the start
of transfusion, the transfusion should be stopped. Acute hemolytic reaction or bacterial
contamination should be suspected if there is a greater rise in temperature, or more serious
symptoms (e.g., rigors).
 Respiratory Distress/Dyspnea
Dyspnea, or shortness of breath, is a concerning sign that can often be seen with more severe
reactions including anaphylaxis, TRALI, and TACO. It can also be seen by itself without
accompanying symptoms.
 Hypotension
Hypotension can be seen with an acute hemolytic reaction, septic transfusion reactions,
anaphylaxis, and TRALI. They have also been reported without the presence of any other
associated transfusion reaction.
  Hypothermia
Hypothermia can be seen with large volume transfusions of refrigerated products. The only
intervention needed is warming the patient and/or blood product.
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Treatment / Management
When a transfusion reaction is suspected, the transfusion should be immediately stopped, and the
intravenous line should be kept open using appropriate fluids (usually 0.9% saline). A clerical
check should be performed by examining the product bag and confirming the patient’s
identification. The patient’s vital signs should be monitored and recorded at 15-minute intervals.
A post-transfusion blood sample should be drawn and sent to the lab, in addition to sending the
bag and tubing if possible. The blood bank generally completes additional testing and clerical
checks to rule out an incompatible transfusion.
Treatment of specific transfusion reactions is most often supportive. For example, antihistamines
(such as diphenhydramine) can be given for a mild allergic reaction, or an antipyretic can be
given for a non-hemolytic febrile transfusion reaction.[9][15]
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Differential Diagnosis
 Anaphylaxis
 Disseminated intravascular coagulation
 Hemolytic anemia
 Septic shock
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Complications
 Disseminated intravascular coagulation
 Lung injury
 Renal failure
 Hemolysis
 Death
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Pearls and Other Issues

Transfusion reactions are influenced by many factors including the type of component being
transfused, the storage requirements, and the patient’s co-morbid conditions at the time of
transfusion. Understanding how to quickly identify transfusion reactions and appropriately
manage and treat the patient ensures optimal patient care.
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Enhancing Healthcare Team Outcomes

Blood transfusions are often necessary in medicine, and all healthcare workers have to be
familiar with transfusion reactions. Patient on any ward can receive a blood transfusion and
similarly all nurses have to know the potential complications and how to manage them. The
majority of blood transfusion reactions occur because of a clerical/nursing error. While
some reactions can be severe and lead to death, many transfusion reactions are benign.
Anaphylactic reactions from a blood transfusion are very rare but often result in a fatality. Other
reactions include TRALI which ranges from 1-9% and often requires intensive pulmonary
support to prevent a fatal outcome. The incidence of bacterial contamination is rare but can occur
from both gram-negative and gram-positive organisms. The key to reducing the morbidity is
vigilance on the part of the nurse. During the patient medical history, one should ask about prior
transfusions and any complications. If there is ever any doubt about the patient's blood group or
the blood type being administered, the laboratory should be asked to reconfirm the status.[16]
[17] (Level V)