TRANSFUSION REACTIONS

Acute Hemolytic Transfusion Reaction

Lecture 10
o AHTR consists of acute hemolysis with
Services is to provide blood products for accompanying presenting symptoms within
transfusion and follow the transfusion process to 24 hours of transfusion.
assure that the products are administered in the o Etiology: immune or nonimmune
safest possible manner. In addition, transfusion of o Pathophysiology: interaction of preformed
any blood product should provide maximum benefit antibodies in the recipient with the donor red
to its recipient with minimum complications or side cell antigens
effects. o Most severe reactions = ABO
incompatibility
The entire process, beginning with donor o A small amount of incompatible blood, as
recruitment and screening through posttransfusion little as 10 mL, can cause rapid hemolysis.
monitoring of the recipient, is focused on a positive,
uneventful outcome. A transfusion reaction is
defined as any unfavorable response in a blood or
blood product recipient. Transfusion reactions
display a range of symptoms from mild exacerbation
up to and including death. (S. Whitlock)
Adverse Effects of Blood Transfusion
o Acute Transfusion Reaction - reaction with
signs and symptoms present during or
within 24 hours of transfusion
o Delayed Transfusion Reaction - reaction with
signs and symptoms present after 24 hours
of transfusion.
SYMPTOMS DIAGNOSIS
immune or nonimmune Fever/chills DAT (+)
infectious or non-infectious Back pain ↓ Hgb
Hemoglobinemia ↑ LDH
↑ Bilirubin
Acute Transfusion Reactions Hemoglobinuria
Hypotension, renal ↓ Haptoblogulin
 Acute Hemolytic Transfusion Reaction failure
 Transfusion-Associated Sepsis Shock DIC
 Febrile Nonhemolytic Transfusion Reaction
 Allergic Transfusion Reactions
 Transfusion-Related Acute Lung Injury
o Membrane attack complex (lytic arm) of the
 Transfusion-Associated Circulatory Overload complement cascade causes
 Adverse Events Associated with Massive Transfusions hemoglobinemia and hemoglobinuria =
hallmark of intravascular hemolysis
o DIC – proteins that control blood clotting
become overactive.
o LDH is often used as a marker of tissue
breakdown as LDH is abundant in red blood
cells and can function as a marker for
hemolysis. A blood sample that has been
handled incorrectly can show false-positively
high levels of LDH due to erythrocyte
damage.

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 o Haptoglobin is primarily produced in the o It occurs when a bacteria-contaminated
liver and is functionally important for binding blood component is transfused.
free hemoglobin from lysed red cells in o Mortality risks include:
vivo, preventing its toxic effects.  Contamination by a gram-negative
o When an immune AHTR is suspected, the bacilli
transfusion must be discontinued  patient’s age
immediately, a clerical verification  volume transfused
performed, and notify the patient’s physician.  PLT storage time
o Intravenous access should be maintained for
Sources of bacterial contamination:
further or supportive therapy.
TREATMENT PREVENTION
 Skin flora
Discontinue transfusion  GUT flora associated with transient
Follow SOP for bacteremia in an asymptomatic donor
Maintain vascular access
identification of the
Maintain blood pressure  Bacterial endotoxins generated during
patient
Maintain renal blood flow storage
Treat DIC if present

SYMPTOMS Dx TREATMENT PREVENTION

Acute Nonimmune Hemolytic Transfusion Reaction  Fever/chills  DAT (-)  Discontinue
 Hypotension  Gram stain transfusion
o Most frequently presents as asymptomatic  Shock blood bag  Maintain
 Culture vascular
hemoglobinuria blood bag access
Occasionally associated with renal Follow SOP
o  Culture  Consider
for collection
dysfunction and rare related death has been patient initial
broad-
reported spectrum
o It can be caused by chemical damage or antibiotic
mechanical damage: coverage
*A broad-spectrum antibiotic is an antibiotic that acts on the
 Improper shipping or storage
two major bacterial groups, gram- positive and gram-negative,
temperature or any antibiotic that acts against a wide range of disease-
 Incomplete deglycerolization of causing bacteria.
frozen RBC
 Small bore of needle used Febrile Nonhemolytic Transfusion Reaction
 Improper use of blood warmer o An acute complication of transfusion
o Its pathophysiology is independent of the presenting with at least a 1°C increase in
presence of antibodies body temperature.
o Other causes: bacterial contamination o An increase in body temperature in a
hypothermic patient to normal body
SYMPTOMS Dx TREATMENT PREVENTION
temperature SHOULD NOT be considered
 Asymptomatic DAT  Discontinue as FNHTR.
 Hemoglobinuri (-) transfusion
Follow SOP for o Etiology: white blood cell-related
a  Maintain vascular
equipment
access
operation
mechanisms
 Maintain renal o Immune mediated and is due to the presence
blood flow
of preformed antibodies reacting against
white cells in the blood component
Transfusion-Associated Sepsis o Related to platelet storage changes, which
involve the production and release of
o An acute nonimmune transfusion reaction biologically active cytokines.
presenting with body temperatures usually o Occasionally, shaking chills is the only
2°C or more above normal and rigors that initial presenting symptoms, followed by an
can be accompanied by hypotension.

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 increase in body temperature up to SEVERE ALLERGIC REACTION
SYMPTOMS Dx TREATMENT PREVENTION
30mins. After discontinuing the transfusion.  Angioedema  DAT (-)  Discontinue
o FNHTR is self-limited, as fever will resolve (Periorbital edema,  IgA transfusion
tongue swelling) deficiency  Maintain
within 2 to 3 hours.  (Bronchoconstrictio work up vascular
For IgA
o Since rigors do not respond to antipyretic n) Wheezing when access
absolute
 Gastrointestinal indicated  Treat with
therapy, meperidine may quickly resolve the symptoms subcutaneo
deficient
patients,
fever.  Cardiovascular us
provide I gA
o Leukoreduction before storage before instability epinephrine
deficient
(Hypotension,  Maintain
their release of cytokines, thus making it the blood
cardiac arrhythmia, blood
components
most effective in preventing and reducing loss of pressure
consciousness,  Provide
incidence of FNHTR. shock, cardiac respiratory
arrest) support
SYMPTOMS Dx TREATMENT PREVENTION Symptoms associated with more severe reactions will
 Fever/chills  DAT  Treat with
Pre-storage generally appear shortly after the transfusion has been
 Nausea/vomiting (-) antipyretics
leukoreduction started and minimal volume has been transfused.
 Tachycardia  For rigors,
of PRBC and
 Tachypnea treat with
platelets Most classic example of a triggering factor for severe
 ↑ Blood pressure meperidine
ALTR is associated with IgA-deficiency-related
anaphylactic reaction
Allergic Transfusion Reactions
Angioedema – rapid edema or swelling of the area
o It occurs as a response of recipient beneath the skin or mucosa
antibodies to an allergen present in the
blood component. Bronchoconstriction - the constriction of the
o It can range from minor urticarial effects to airways in the lungs due to the tightening of
fulminant anaphylactic shock and death. surrounding smooth muscle, with consequent
o Pathophysiology: due to activation of mast coughing, wheezing, and shortness of breath
cells in the recipient triggered most
frequently by an allergen present in the
plasma of the blood component. Patient TREATMENT PREVENTION
preformed IgE antibodies interact with the Discontinue transfusion
donor-derived allergen Maintain vascular access
For IgA absolute deficient
Treat with subcutaneous
o The binding of the allergen to the IgE bound patients, provide IgA
epinephrine
to the mast cell results in the release of deficient blood
Maintain blood pressure
histamine and other granule contents (type components
Provide respiratory
I hypersensitivity reaction) support
Washed blood component is suggested.
Anaphylaxis causes your immune system to release a
flood of chemicals that can cause you to go into shock – Transfusion-Related Acute Lung Injury
low blood pressure and your airways narrow, blocking
breathing. o Consists of an acute transfusion reaction
presenting with respiratory distress and
severe hypoxemia during or within 6 hours
MILD ALLERGIC REACTION of transfusion in the ABSENCE of other
SYMPTOMS Dx TREATMENT PREVENTION causes of acute lung injury.
 Weals/Hives  Clinical  Temporary
 Erythema diagnosis discontinue For repeated
o Accompanied by fever or hypotension it is
 Pruritus  DAT not transfusion reactions, now considered the leading cause of
required  Treat with consider
antihistamines premedication
transfusion-associated fatalities,
 If symptoms with anti- SURPASSING ABO incompatibility and
improve restart histamines
transfusion
bacterial contamination.
Symptoms associated with milder reactions may occur any time during
or after the transfusion. If symptoms do not subside, the transfusion
must not be restarted.

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Acute Respiratory Distress Syndrome (ARDS) is is exceeded, manifesting as congestive
a severe lung condition. It occurs when fluid fills up heart failure.
the air sacs in your lungs. Too much fluid in your o TACO is also associated with increased
lungs can lower the amount of oxygen or increase morbidity and mortality
the amount of carbon dioxide in your bloodstream. o TACO typically occurs in patients who
receive a large volume of a transfused
o Acute lung injury is a disorder of acute
product over a short period of time, or in
inflammation that causes disruption of the
those with underlying cardiovascular or renal
lung endothelial and epithelial barriers.
disease.
o Immune TRALI
o These signs and symptoms may occur
 antibody-mediated
during or after transfusion
 antibodies against the HLA or HNA in
o Brain Natriuretic Peptide (BNP), also
the transfused blood component
known as B-Type Natriuretic Peptide, is a
react with recipient leukocytes,
hormone secreted by cardiomyocytes in the
causing aggregates that occlude the
heart ventricles in response to stretching
pulmonary circulation.
caused by increased ventricular blood
o Nonimmune TRALI volume.
 may result in priming of the patient’s
neutrophils SYMPTOMS Dx TREATMENT PREVENTION
 Severe  CXR:  Upright  Slower
 activation of the primed neutrophils. hypoxemia pulmonary posture transfusion
 Cough, edema,  Supplemental rate
Though the pathogenesis is not fully understood, two headache, cardiomegaly, oxygen  Transfuse in
chest distended Diuresis smaller
different hypothetical pathways have been tightness pulmonary volumes
postulated.  ↑ Blood artery
Pressure  Brain
Noncardiogenic Pulmonary Edema (NCPE) is a  Jugular natriuretic
vein peptide (BNP)
specific form of pulmonary edema that results from distension
an increase in permeability of the normal alveolar-  ↑ Central
venous
capillary barrier pressure

SYMPTOMS
 Severe
hypoxemia
CXR:
Dx

bilateral
TREATMENT
 Discontinue
transfusion
PREVENTION
 Use male only
plasma
Delayed Transfusion Reactions
 No evidence infiltrates  Maintain  Exclude or Delayed Serologic/Hemolytic Transfusion Reaction
of left atrial Donor test vascular screen female
hypertension for access platelet donors
HLA/HN A  Supplemental
o Defined as the detection of “new” red cell
antibodies oxygen antibodies AFTER 24 hours of transfusion.
Recipient Mechanical
test for ventilation
It may be discovered when a new sample is
HLA/ HNA tested during a request for a type and
antigens
crossmatch and the hemoglobin levels are
A pulmonary infiltrate is a substance denser than air,
lower than expected for the transfusion
such as pus, blood, or protein, which lingers within the
parenchyma of the lungs.
interval.
SYMPTOMS Dx TREATMENT PREVENTION
Leukocyte antibodies are found with highest frequency
in multiparous female donors, with the incidence  Asymptomatic  (+) Ab  As needed  Accurate
increasing with the increased number of pregnancies  Fatigue screen/DAT  Transfuse record-
 ↓ Hgb antigen keeping
negative, AHG  Obtain
Transfusion-Associated Circulatory Overload crossmatched transfusion
compatible history
o Occurs when the patient’s cardiovascular PRBC  Limit
transfusions
system’s ability to handle additional workload

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Most often, the only presenting sign is an unexplained or Iron Overload
unexpected drop in hemoglobin or hematocrit.
o A delayed, nonimmune complication of
Transfusion-Associated Graft-Versus-Host Disease transfusion, presenting with multi-organ
damage secondary to excessive iron
o Defined as a delayed immune transfusion
accumulation.
reaction due to an immunologic attack by
o Each unit of red blood cells contains
viable donor lymphocytes contained in the
approximately 250 mg of iron.
transfused blood component AGAINST the
o After a 10 to 15 red cell transfusions, excess
transfusion recipient.
iron is present in the liver, heart, and
o HLA antigen difference between donor and
endocrine organs.
recipient
o At Risk: Patient having chronic red cell
o Presence of donor immunocompetent cells in
transfusions causing anemia.
the blood component
o Recipient incapable of rejecting the donor SYMPTOMS Dx TREATMENT PREVENTION
immunocompetent cells  Multi-organ  High ferritin  Use of iron-  Prophylactic use
o Conditions that will result to TA-GVHD to failure levels chelating of iron- chelating
agents agents
develop in a recipient = Fresher blood  Red cell exchange
components contain more viable T-
lymphocytes
SYMPTOMS Dx TREATMENT PREVENTION

 Maculopapular  Pancytopenia  N/A  Gamma Parenteral deferoxamine

Rash  Elevated liver irradiation
 Fever function tests of cellular Oral deferiprone
 Watery  Identify donor blood
diarrhea engraftment components Oral deferasirox
as indicated
It combines with iron in the blood. The combination
of iron and deferasirox is then removed from the
Post-Transfusion Purpura body by the kidneys.

o Defined as a delayed immune complication Hemochromatosis is an iron overload disorder in

of transfusion that presents with profound which a person absorbs too much iron from the food
thrombocytopenia 1-24 days after a blood and drink they consume. Left untreated, it can
transfusion. damage various organs in the body. The skin takes
o Occurs when a patient who is previously on a bronze colour.
sensitized to human platelet antigens by
pregnancy or transfusion is re-exposed via Investigation for Transfusion Reaction
a transfusion.
o Investigation of transfusion reactions
o This is characteristically a RBC or whole
requires immediate action both by the
blood transfusion, expressing that human
administering personnel and the laboratory.
platelet antigen specificity and causing an
o The RMT will NOT be involved with detection
anamnestic immune response, destroying
of symptoms of a transfusion reaction nor will
NOT ONLY transfused but also the
he or she initiate the immediate steps to stop
autologous platelets.
the transfusion and begin an investigation or
SYMPTOMS Dx TREATMENT PREVENTION institute treatment.
 Bleeding  Thromobocytopenia  Intravenous  Limit o The focus of this investigation focuses on the
 HPA antibodies immunoglobulin transfusions detection of a hemolytic reaction.

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 Test for investigation of Transfusion Reaction

 ABO and RH
 Patient’s pre transfusion sample
 Patient’s post transfusion sample
 Donors segment
 Compatibility Testing
 Donor’s pre transfusion sample
 Donor’s post transfusion sample
 Donor segment
 Additional Tests
 Serum Haptoglobin and Bilirubin
 Urine Hemoglobin
 Hemoglobin and hematocrit
 Inspection of Donor Unit
 Gram Stain and Blood culture
 Culture of the Transfused Unit

o Reidentification of the recipient and the unit

being incriminated. If a discrepancy is
detected, it is documented and reported to
the physician.
o Recipient’s physician and the transfusion
service are notified.
o The physician assesses the recipient’s
symptoms and initiates intervention if
necessary.
o The intravenous line is kept open and saline
or other FDA approved solution is infused.
o If the signs and symptoms indicate that the
possibility of a serious complication—such
as acute HTR, TRALI, sepsis, anaphylaxis
or other serious complication—the following
items should be forwarded to the transfusion
service for evaluation:
 A post-reaction blood sample
(sample should be properly collected
and labeled)
 Transfusion container and
administration set
 Attached intravenous solutions
 All related forms and labels
 First voided post-reaction urine (in
some circumstances)

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