Acute, Non-Infectious Transfusion Reactions
Associate Medical Director, Centralized Transfusion Service
Adverse events associated
with blood transfusion therapy can be classified based on time of onset
(acute vs. delayed) and etiology (immune vs. non-immune). Acute transfusion
reactions generally occur during or within 2 hours of transfusion.
Transfusion reaction manifestations may vary with the type of blood product
transfused and the clinical condition of the recipient.
DESCRIPTION AND MANAGEMENT
When a transfusion reaction
is suspected, the transfusion must be discontinued immediately, while evaluation of the event is
performed. (Only mild allergic reactions may be restarted.) A normal saline
drip should be started to maintain IV access, while a clerical check is
performed at the bedside to verify that the unit being transfused is the
unit intended for that particular patient (transfusion compatibility tag vs.
patient identification band). Post-reaction blood and urine samples, along
with the blood bag implicated in the reaction, should then be sent to the
blood bank for further testing. The initial transfusion reaction evaluation
by the blood bank is designed to rule out a hemolytic transfusion reaction.
Once the laboratory evaluation is completed, the blood bank physician will
review the case, provide a final diagnosis, and issue recommendations.
Acute Febrile Reactions
Because fever (alone or
accompanied by chills/rigors) may be the first manifestation of a
life-threatening reaction (e.g. acute hemolysis, transfusion-associated
sepsis, transfusion-related acute lung injury), as well as, the more benign
and common febrile non-hemolytic transfusion reaction (FNHTR),
any significant increase in temperature (≥1oC or 2oF)
occurring during transfusion must be taken seriously.
Acute Hemolytic Transfusion
Besides fever and chills, other presenting signs/symptoms of an AHTR
include: hypotension, flank pain, hemoglobinuria and hemoglobinemia. The
most severe reactions result from transfusion of ABO-incompatible red cells,
with resultant complement-mediated intravascular hemolysis and the release
of vasoactive amines (e.g. histamine) and other mediators/cytokines, which
cause vasodilation, hypotension, and contraction of bronchial and intestinal
smooth muscle. The combined effects of these changes can bring about renal
damage, DIC, shock and even death. These catastrophic consequences can be
observed with transfusion of as little as 10-15 mL of incompatible blood. In
an anesthetized recipient, red urine or microvascular bleeding (DIC) may be
the only observable manifestations of an AHTR.
Early recognition and
management of an immune AHTR is essential in minimizing/ preventing
associated morbidity/mortality. It is critical to maintain adequate urine
output with fluids and diuretics (furosemide). For treatment of hypotension,
low-dose dopamine is preferred (enhances renal perfusion).
AHTRs may also arise from
non-immune, in vitro hemolysis (use of non-isotonic IV solutions, heat,
cold, or mechanical stress), most often manifested by asymptomatic
hemoglobinuria. These tend to be self-limited and usually resolve within 24
hours. Maintenance of adequate renal perfusion is the focus of treatment,
especially for patients with compromised renal function.
Transfusion Reaction (FNHTR): FNHTRs are the most frequent
adverse reactions observed with transfusion. Described as a temperature
increase of ≥1ºC (2ºF) in relation to transfusion, they can also be
accompanied by chills/rigors, hypertension, tachycardia and dyspnea. The
symptoms most often present toward the end of the transfusion or within two
hours post-transfusion. Usually self-limited, the symptoms occur secondary
to the effects of cytokines actively released in vivo by interaction of a
recipient's preformed anti-leukocyte antibodies with white cells present in
the transfused blood component or from passively acquired cytokines in the
product. The fever can be treated with antipyretics and meperidine has been
found to be effective in treating the associated rigors. In those patients
with repeated reactions, it may be beneficial to premedicate with
antipyretics and/or use leukoreduced blood products
reactions range from mild itching and urticaria (hives) to generalized
reactions with bronchoconstriction (wheezing), hypotension and shock.
Mild Allergic Transfusion
Reaction: Mild allergic transfusion
reactions are frequently observed with transfusion and thought to result
from an allergic, antibody-mediated response to donor plasma proteins. They
are characterized by pruritis and urticaria, during a transfusion.
Antihistamines are generally effective in treating and/or preventing these
Generalized Allergic &
Anaphylactic Transfusion Reactions: Generalized allergic reactions
occur less frequently and, in rare cases, can progress rapidly to full-blown
anaphylactic shock. Symptoms include: wheezing, GI upset and hypotension
with no fever. Occurring primarily as an isolated episode to a particular
donor, the causative allergen is seldom identified. These reactions can
occur with as little as 5 mL of blood component transfused. Antihistamines,
steroids and, in severe cases, epinephrine are useful in
treatment/prevention of these reactions. When these measures are
ineffective, the use of washed red blood cells and platelets may be
necessary. Rarely, anaphylactic reactions due to anti-IgA antibodies in IgA-deficient
recipients are seen. This should be suspected in previously untransfused
patients. In such cases, specialized blood products – double-washed red
cells/platelets and/or blood products derived from IgA-deficient donors –
are required, in addition to steroid premedication.
These reactions are
characterized by the development of shortness of breath, most often
occurring toward the end of a transfusion or within two hours after
transfusion. They differ in the changes in the systemic blood pressure and
response to diuretics. (FNHTRs may also present with dyspnea.)
Circulatory Overload: Circulatory overload most often
manifests as cardiogenic pulmonary edema secondary to a rapid infusion or
large volume transfusion in a patient with cardiorespiratory compromise.
Respiratory distress and hypertension are seen during or shortly after
transfusion. These patients usually respond to diuresis and respiratory
support with resolution of symptoms.
Transfusion Related Acute
Lung Injury (TRALI):
TRALI is usually attributed to the interaction of passively
acquired donor antibodies directed against the recipient’s white cells.
Symptoms include: marked dyspnea, hypoxemia, and bilateral non-cardiogenic
pulmonary edema. Fever and hypotension may also be present. Diuretics are
ineffective and the patients classically require ventilatory support for 3-4
days followed by resolution of symptoms.
While the majority of acute
transfusion reactions are transient and do not result in lasting sequelae,
similarities in the presenting signs and symptoms among the various types of
reactions make it impossible to differentiate a relatively benign event from
the early stages of a severe, life-threatening transfusion reaction.
Therefore, prompt recognition and appropriate action to limit exposure,
initiate investigation by the blood bank and manage clinical manifestations
of suspected transfusion reactions is essential in minimizing the potential
adverse effects of transfusion and providing quality patient care.
Manual, 14th Edition, 2002.
Donald L. Kelley, M.D., MBA: email@example.com
For questions regarding this TMU, please
Ileana Lopez-Plaza, MD at: (412) 572-0559.
Copies of the Transfusion Medicine Update can be
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by calling Deborah Small:
(412)209-7320 or by e-mail: firstname.lastname@example.org
© 2003, Institute For Transfusion
Editor: Donald L. Kelley, M.D., MBA: email@example.com