ADVERSE TRANSFUSION

REACTIONS (ATR) AND ITS

MANAGEMENT
Herwindo Pudjo Brahmantyo

Hematology - Medical Oncology Division, Dept. of Internal Medicine

Saiful Anwar General Hospital – Brawijaya University, Faculty of Medicine
 Introduction
• Transfusion did the first time at 1667
• Rapidly grow up after the first World War  Massive
transfusion
• Blood and blood products provide unique and life‐saving
therapeutic benefits to patients.
• However, due to resource constraints or even the source
of human product, it is not always possible for the blood
product to reach the patient at the right time or without
any risk

Transfusion Reaction
 Transfusion Risk
• Receiving the wrong blood component: 1 in 16,500 to 1 in 77,000
• ABO Mismatching: 1 in 100,000
• Headache, mild fever, itching & hives: 1-3 in 100
• Death risk due to Incomptability Blood Component Transfusion
(IBCT): 1 in 1.500.000
• HIV / AIDS : Approximately 1 in 35.2 million
• Hepatitis C : Approximately 1 in 3.2 million
• Hepatitis B : Approximately 1 in 1.9 million

Data source: ARCBS 2006-2007

 Adverse Transfusion Reactions
• Adverse Transfusion Reactions is define as any unfavorable
event occurring in a patient during or after blood transfusion
• 2 type of ATR: Imunologic & Non imunologic
• Imunologic ATR: the cause of ATR is an immunological
mechanism.
• Non-imunologic ATR: ATR caused by ‘physical effects‘ from
blood component or infection.
• According to the time of transfusion :
– Acute or Immediate (<24 jam)
– Delayed (>24 jam)
 AHTR:
Acute Hemolytic Transfusion Reactions
• AHTR is hemolytic reaction that occurred within 24 hours of the
initiation of the transfusion
• The most cause: blood group incompatibility
• Incidence:1 in 38,000 RBCs transfusions
• Caused by clerical or clinical error; i.e. misidentification patients
(In blood bank or In the ward)
• Prevention:
– Positive patient identification
– Sample is labeled and packed with the blood request form in one container
at bedside
– Blood bags are packed in one container with the blood request form
 AHTR : How to manage ?
• Stop transfusion immediately if AHTR suspected.
• Check the possibility a clerical error (identity of patient vs.
patient identity on blood product label, etc).
• Notify hospital transfusion service (blood bank).
• Send samples to blood bank to re-check ABO-group.
• Return residual of blood product(s) and tubing (clamped) to the
blood bank
• Send first post-transfusion urine sample.
• Provide supportive care :
– Maintain good urine output
– Manage DIC and hemorrhage as clinically indicated
 DHTR = Delayed Hemolytic Transfusion
Reactions
• Hemolytic reaction occurring more than 24 hours after
transfusion, in a patient who has been immunized to minor red
cell Ag (E, Jk, c, Fy, K) by previous transfusion, pregnancy or
transplant.
• The antibodies may be undetectable by routine blood bank test
• Red cell transfusion can induce a secondary immune response
that boosts the antibody level results in intravascular hemolysis.
• Incidence: 1 in 6715 units of RBCs transfusion
• Clinical presentation: hemolytic anemia within 3 days to 2 weeks
after transfusion
 DHTR : How to prevent and manage ?
• Prevention: Medical history of previous transfusions,
pregnancies, transplants and transfusion reactions should be
taken.
• Request RBC to the blood bank with special requirement.
• Use of antibody screening methods with maximal sensitivity. It
should be performed to the patient:
– who have previously received RBCs transfusion, or
– who have known risk factors (pregnancy or previous RBCs transfusion,
transplantation).
• Management: transfusion with compatible-
Ag negative blood for pts with persistent-
anemia.
 FNHTR = febrile non hemolytic
transfusion reaction
• FNHTR defines as fever (>1oC rise) during or soon after transfusion and
having no medical explanation other than blood transfusion.
• Incidence:1% of transfusions.
• Are caused by leukocyte antibodies and cytokines in the recipient that react
with leukocytes in the transfused components (donors).
• This reaction is unpleasant but not life threatening;
• Fever or rigors could be the first warning of a severe acute reaction.
• Prevention: transfusion with leuco-depleted red blood cells.
• Management:
– Premedication with acetaminophen in patients with documented histories of FNHTR.
– Meperidine (Demerol®) 25-50 mg IV may be effective for severe rigors
 Allergic Reactions
• Probably it is the most frequent of ATR (1-2%)
• Clinical presentations: range from hives (urticarias) to severe
respiratory or anaphylactic.
• IgE or IgG antibodies are involved in many allergic reactions.
• Allergic reactions are more likely to occur from components that
have been stored longer because histamines and vasoactive
substance produced by leukocyte increase during storage.
• Prevention:
– Use plasma-deficient blood components or washed blood components
– Premedication with antihistamin for patients with documented histories of
allergic reactions
 Anaphylactic and Anaphylactoid
Reactions
• 1 in 20.000 to 1 in 47.000 transfusions.
• Antibodies against IgA, complement C4, haptoglobin, or other
unknown plasma proteins.
• Immediate hypersensitivity type but clinically more severe,
involving any organ of the body.
• Anti IgA titers are not predictive of the likelihood of a reaction.
• Prevention: use washed-red blood cells to remove all plasma
IgA or use plasma components prepared from IgA-deficient
donors.
• Management: according to treatment of anaphylactic Rx.
 Alloimmunization
• As a result of exposure to blood  patients may form antibodies to RBCs;
lymphocyte, granulocyte, or platelet surface antigens; or plasma proteins.
• Antibody formation depends on the immunogenicity of the antigen and the
ability of the individual to mount an antibody response.
• Clinical presentation: generally it doesn’t clinical manifestations yet
• Later it can cause clinical problem if the patient: requires subsequent
transfusions or organ or tissue grafts, or becomes pregnant.
• Prevention: Cannot be completely prevented
• Strategy :
– The matching of donor and patients RBC phenotypes
– The use of single-donor platelets and leuco-depleted blood components to
prevent platelet refractoriness. (HLA / HPA matched)
 TRALI = Transfusion Related Acute Lung
Injury
• Acute insufficiency respiratory with diffuse pulmonary infiltrates on x-
ray and the general clinical presentation of non-cardiogenic pulmonary
edema which begins 4 to 6 hours of initiating the transfusion.
• Incidence: 1 in 5.000 transfusions (Popovsky), but underreported and
underdiagnosed
• Pathophysiology: passive transfusion of donor antibodies of HLA Class
I & II/Granulocyte Antibodies (90%)  activate complement  leads
to Neutrophil aggregation/ sequestration in the Lungs  neutrophil
enzymes damage endothelium  pulmonary edema
 TRALI :
How to prevent & manage ?
• If TRALI is caused by patient antileukocyte Ab, leuco-depleted
blood component should be used.
• If TRALI is caused by donor antileukocyte Ab, no special blood
component preparations in the future.
• Management:
– Ventilatory support as required
– Maintenance of hemodynamic status: Inotropes, vasopressors
– 80% of patients show clinical improvement within 48-96 hours
– In most patients, there are no long-term complications.
– Fatal cases about 5-10%
 Post Transfusion Purpura (PTP)
• PTP is purpura caused by a rapid onset of
thrombocytopenia that occurred within 7-14 days after
platelet transfusions.
• The thrombocytopenia is usually self-limited.
• During PTP treatment period, platelet transfusion should
be avoided.
• Furthermore, there are no good ways to prevent post-
transfusion purpura.
• Record patient history of prior transfusion and any adverse
reactions
 TA-GVHD = transfusion-associated
graft-versus-host disease
• The syndrome characterized by: fever, liver dysfunction, skin rash,
diarrhea and marrow hypoplasia (pancytopenia), diffuse mucositis,
and bleeding
• Etiology: viable T-lymphocytes (HLA-haploidentical) from the donor-
blood components.
• Patients at risk: Immunocompromized pts, marrow or stem cell
transplant recipients, Congenital T-cell deficient (DiGeorge,s),
Neonatal/intrauterine transfusions, Getting blood from first-degree
relative, Hodgkin,s disease
• Develop begins less than 30 days of following transfusions (1-2 weeks
after transfusion)
• Prevention: irradiating the blood components-
prior to transfusion.
 TACO = Transfusion-Associated
Circulatory Overload
• TACO: LVF caused by circulatory overload due to fluid excessive or too
rapid blood transfusion
• Especially at children <3 yo, elderly patients (>60 yo) and patients with
chronic normovolumic anemia, cardiac disease, thalassemia major or sickle
cell disease.
• The usual rate of transfusion is about 200 mL per hour. In patients at risk or
with histories of circulatory overload, rates of 100 mL per hour or less are
appropriate.
• Donor units should be split into to permit transfusion for longer time period.
• Red blood cells (PRCs) should be used instead of whole blood.
 Bacterial Contamination
Reactions
• Although the frequency of bacterial contamination of blood
components is low this type of septic reaction can have a rapid
onset and lead to death.
• Is caused by endotoxin produced by bacteria capable of growing
in cold temperatures (psychrophilic) such as Pseudomonas
species, Escherichia coli and Y.eterocolitica.
• Clinical signs and symptoms of septic reactions usually appear
rapidly during transfusion or within about 30 minutes after
transfusion.
 Bacterial contamination :
How to prevent ?
• Bacterial contamination of blood components usually occurs at
the time of phlebotomy, during the component preparation or
processing, or during thawing of blood components in water-
baths.
• Prevention:
– Strict adherence to policies and procedures regarding blood component
collection, storage, handling, preparation.
– Prudent transfusion practices.
– Visual observation of RBC units for color change at the time of issue for
transfusion.
– Make sure the blood components are infused within standard allowable
maximum time limits (usually 4 hours).
 Physically or chemically
induced transfusion reactions
• Red cells are susceptible to membrane damage and
intravascular lysis by hypertonic or hypotonic solutions, heat
damage, freezing damage in the absence of a cryoprotective
agent, or mechanical damage such as that caused by roller
pumps in a blood pump.

• Prevention :
– Use NaCl 0,9% infusion
– Close monitoring of RBC transfused through blood pumps.
 Hypothermia
• Hypothermia: a core body temperature of less than
35oC
• Prevention :
– over 1 hour transfusion or at a flow rate in an adult
of about 5 mL per minute or less because the cold
blood is effectively mixed with the patient’s body-
temperature blood.
– Use Blood warmers
 Conclusions
• Adverse Transfusion Reactions (ATR) is any unfavorable event occurring in
a patient during or after blood transfusion
• The most common ATR are allergic reaction and febrile reaction.
• Strict adherence to policies and procedures of blood transfusion can reduce
the incidence of ATR
• It is important to recognize type of ATR promptly and managed
appropriately to reduce morbidity and mortality
• General management whenever an ATR is suspected include: stop
transfusion, monitor vital signs, suportive treatment, re-check name and
other identities of patient with blood-product label, and specific treatment
according to the type of ATR itself.