TRANSFUSION REACTIONS AND

THEIR MANAGEMENT

By
AIDA ALAUDIN
Transfusion Reaction
 is any unfavorable transfusion-related
event occurring in a patient during or after
transfusion of blood components

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Immediate and Delayed Transfusion
Reaction
Immediate Delayed

Immune Effects
AHTR DHTR
FNHTR Alloimmunization
Allergic reaction PTP
Anaphylaxis & anaphylactoid reaction TA-GVHD
TRALI
Nonimmune Effects

Bacterial contamination Iron overload

TACO TTV

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IMMUNE HAEMOLYTIC TRANSFUSION
REACTION

Defined as the destruction of red cells in the

recipient of a transfusion caused by immune
alloantibodies of red cells.
 Acute Hemolytic Transfusion
Reaction
Pathophysiology

Ab (in recipient serum) + Ag (on RBC donor)

-Neuroendocrine responses
-Complement Activation
-Coagulation Activation
- Cytokines Effects

Acute hemolytic transfusion reaction

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Pathophysiology


Two mechanisms for RBCs destruction

 1) Intravascular hemolysis

 2) Extravascular hemolysis

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Signs and Symptoms of
AHTR
Chills , fever Feelings of doom
Hypotension Agitation
Generalized bleeding Facial flushing
Hemoglobinemia Restlessness
Hemoglobinuria Dyspnoea
Renal failure Abdominal , chest or
DIC back pain
 Pain along infusion
 vein
 Nausea,vomiting
Diarrhoea
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Acute Hemolytic Transfusion
Reactions
v Acute onset within minutes or 1-2 hours
after transfuse incompatible blood



v Most common cause is ABO-incompatible
transfusion

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Management of AHTR
Perform bedside clerical checks
 - check compatibility label to ensure that
it
 corresponse with patient’s data
 - if a mistake is found, inform blood bank
Return unit, set to blood bank
Collect appropriated post transfusion blood
 sample for evaluation
Document reaction

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 Laboratory investigation for
AHTR
 10 ml of clotted blood labelled as post Tx sample 1 for
 - repeat ABO and Rhesus grouping

 - repeat compatibility test

 - Ab screening and Direct Coomb’s Test

 Send another sample 24 hours later and label as post Tx sample 2

 Send FBC in EDTA tube
 Send blood sample for biochemistry lab for
 - serum electrolytes and renal profile
 - serum bilirubin
 Send blood for DIVC screening

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 Laboratory investigation for
AHTR
 Urine output should be monitored and presence of hemoglobinuria noted

 ECG should be done to check for evidence of hyperkalemia

 Urine should be sent to confirm presence of hemoglobinuria



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Treatment of AHTR
Depends on
 Amount of incompatible blood transfused

 Specificity of the offending antibody

 Clinical severity of the reaction

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 Acute Hemolytic Transfusion
Reaction
Treatment
u
Primary concerns :
- vigorous treatment of hypotension
- promotion of renal blood flow

To prevent renal failure

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Treatment of AHTR
Stop the transfusion immediately, inform blood
bank
IV line should be maintained with N/S infusion,
initiall 20-30ml/kg to maintain SBP
Monitor vital signs and strict I/O chart
(maintain urine output at 1-1.5ml/kg/hour
Maintain airway, give oxygen support if
necessary
Administer IV Frusemide 1 mg/kg if urine
output < 1ml/kg/hour
If patient is hypotensive, give inotrope IV
dopamine 1 µg/kg/min
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 AHTR
Prevention
upreventing or detecting errors in every phase of the transfusion

process :
usample acquisition
uat all steps in laboratory testing
uat the time of issue
uat the time of transfusion
uEnsuring that all clinical staff recognize signs and symptoms of
acute reaction

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 Delayed Hemolytic Transfusion
Reaction

Most often the result of an anamnestic

response (transfusion, pregnancy,
transplantation )
Mild clinical signs and symptoms
Unexpected or unexplained decreased in Hb or
Hct after transfusion should be investigate as
possible DHTR

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Delayed Hemolytic Transfusion Reaction
 Pathophysiology
 - 2 types of DHTR

1) secondary (anamnestic) response to
transfused RBCs  3 – 7 day after Tx

2) primary alloimmunization longer
 - Extravascular hemolysis


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 Delayed Hemolytic Transfusion Reaction

Signs & Symptoms

mild fever or fever with chill
mild anemia
mild to moderate jaundice
Uncommon  hemoglobinemia,
Hemoglobinuria, shock, renal failure

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Delayed Hemolytic Transfusion Reaction
 Therapy and Prevention
 - Goal of therapy is prevention
 - Treat severe complication if necessary
 - Alert to history of sensitization
 (previous transfusion, Pregnancy,
transplantation)


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Febrile Nonhemolytic Transfusion
Reaction
( FNHTR)
 Definition
 Temperature increase of more or equal to
1oC associated with transfusion, with no
medical explanation other than blood
transfusion

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 Pathophysiology of FNHTR
- Patients
  - Blood donors
 Leukocyte antibodies  leukocytes in
 (HLA Ab) transfused blood


Activate complement system

C 5a

Pyrogen interleukin-1
(macrophage, monocyte)

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Febrile Nonhemolytic Transfusion
Reaction
Signs & Symptoms
Fever with or without chills
most symptoms are mild
severe reaction :- headache,
hypotension, cyanosis,
tachycardia, tachypnea, dyspnea,
cough


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 Febrile Nonhemolytic Reaction
Diagnosis of FNHTR is by exclusion of other causes of transfusion
reactio as fever could be due to acute hemolytic transfusion
reaction or by bacterially contaminated blood.

Treatment
udiscontinued blood transfusion if the patient has severe reaction
uAntipyretic for fever
uIf patient has experienced 2 or more FNHTR, try

- paracetamol orally I hour before transfusion

- slow transfusion and keep the patient warm
u

Prevention
uusing leucocyte- depleted blood components

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Allergic Transfusion Reactions


Probably the most frequent kind of reaction

Pathophysiology

 Allergen – Reagin (IgE,IgG)

 Complex


 attach mast cell (degranulation)



 histamine/leukotrienes


 Allergic reactions
 (urticaria)
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Allergic Transfusion Reactions
 Signs & Symptoms
 - Urticaria (circumscribed areas of cutaneousedema and
itching)
 - severe reactions are rare


 Therapy & Prevention

 - Stop transfusion temporarily while administering
antihistamine
 (Chlorpheniramine) by slow IV, transfusion can be continued if
 urticariais the only symptom. But if patientdevelops
extensive
 urticariaor a confluent total body rash, it would be necessary
to
 stop the transfusion, even if symptoms have responded to
 treatment.
 - For patients who have had severe or frequent minor urticaria
following
transfusion, administering
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Anaphylactic and Anaphylactoid
reactions
 Anaphylaxis is a rare but life threatening
complication.


 Pathophysiology
- IgE antibody to IgA in donor plasma

 (anti-IgA antibodies)
- immediate generalized hypersensitivity

reaction due to activity of IgE antibodies or the

presence of anti Ig-A in patients with congenital
deficiency of IgA
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Anaphylactic and Anaphylactoid
reactions
Signs & Symptoms

- Anaphylactic  generalized flushing,
coughing, dyspnea, nausea, vomiting,
bronchospasm, chest pain, hypotension,
abdominal cramps, diarrhea, arrythmias,
hypotension, syncope, sndit can progress to
loss of consciousness, shock, and rarely
death.

- Anaphylactoid (less severe)  urticaria,
periorbital swelling, dyspnea, or
perilaryngeal edema
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Anaphylactic and Anaphylactoid
reactions
Therapy and Prevention
Stop transfusion
Keep IV line open with 0.9% saline
Maintain airway and give oxygen, neb Salbutamol
can also be given
Medication :-
 - IM epinephrine then repeat every 10 mins
according to
 blood pressure and pulse rate until improvement
occurs
 - slow IV of antihistamine
Wash RBCs and blood components
Transfuse IgAMD-3
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deficiency
/49
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Transfusion-related Acute Lung Injury (TRALI)
 Acute and severe type of transfusion reaction that can be fatal


 Pathophysiology
 Leukocyte Ab in donor react with pt. leukocytes


 Activate complements


Adherence of granulocytes to pulmonary

endothelium with release of proteolytic enzymes &
toxic O2 metabolites


 Endothelial damage


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 Interstitial
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Transfusion-related Acute Lung Injury
(TRALI)


 Symptoms and signs

Fever
Non-productive cough
Hypotension
Tachypnea
Dyspnea
Diffuse pulmonary infiltration on X-rays
Clinical of noncardiogenic pumonary edema
 - within 4hours of transfusion
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Transfusion-related Acute Lung
Injury (TRALI)
Therapy and Prevention


Manage in ICU setting as oxygen therapy and

assissted ventilation are often required
Adequate respiratory and hemodynamic supportive
treatment
Corticosteroids might be helpful
If antibodies are present, the blood center should
be notified so that the donor will be permanently
deferred from future donations.
Patients who develop TRALI are unlikely to have
another reaction because it is most often donor
specific.

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Transfusion-associated Circulatory
Overload (TACO)
Patients at significant risk


Children
Elderly patients
Chronic anemia
Cardiac disease
Thalassemia major or Sickle cell disease

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Pathophysiology
Volume overload

Congestive heart failure

Pulmonary edema

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Symptoms and Signs
Dyspnea Headache
Coughing Restlessness
Cyanosis Tachycardia
Orthopnea Systolic hypertension
Chest discomfort increase > 50
mm.Hg

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 Therapy & Prevention
T h e ra p y
Rapid reduction of hypervolemia
Respiratory and cardiac support
Oxygen therapy
Diuretic
Therapeutic phlebotomy

Pre ve n tio
 - Use appropiate
n transfusion rate
 - Use appropiate blood components
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Metabolic Reaction
Citrate toxicity
Hyperkalemia
Hypothermia
Coagulopathy in massive transfusion
Air embolism

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Transfusion-associated Graft-versus-Host
Disease ( TA-GVHD)

Patient at risk
 qBone marrow
transplantation
qChemotherapy
qRadiation treatment
qNewborn

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 Transfusion-associated Graft-versus-Host
Disease ( TA-GVHD)
Pathophysiology


 Infusion of Immunocompetent Cells

 (Lymphocyte)

 Patient at risk


 proliferation of donor T lymphocytes



 attack against patient tissue

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Graft-versus-Host Reaction
 Signs & Symptoms

§ Onset ~ 3 to 30 days after transfusion
§ Clinical significant – pancytopenia
§ Other effects include fever, elevated
liver enzymes,
copious watery diarrhea,
erythematousskin erythroderma

and desquamation
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 Graft-versus-Host Reaction
Therapy
Drugs
 :- corticosteroids, methotrexate, azathioprine,
antithymocyte globulin
But no adequate therapy
Prevention
Irradiation of Blood Components (25-30 Gy)

avoid potential fatalities

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Iron 1overload
unit of PRCs has ~ 250 mg of Iron
Removed by body 1 mg / day

accumulate iron Hemosiderosis

iron accumulate in tissue

Hemochromatosis

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Posttransfusion Hemosiderosis
Affected organ :- heart, liver, endocrine glands


Signs & Symptoms

 - muscle weakness, fatigue, weight loss, mild
jaundice, anemia, mild diabetes, and cardiac
arrhythmia


Therapy  Iron – chelating agent

Prevention  transfuse with young RBCs


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Alloimmunization
Result from prior exposure to donor blood
components
Significant complication  even small amount
of blood
Adverse effects may include
difficultyin finding compatible blood
transfusion reaction

platelet refractoriness

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Alloimmunization
Pathophysiology
1stexposure  moderate
production IgM and IgG
antibody by foreign antigens
2nd exposure  rapid
production of large amount of
IgG

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Alloimmunization
Signs & Symptoms
mild slight fever and Hb
severe  platelet refractoriness
with bleeding
Therapy & Prevention
depends on type and severity

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Posttransfusion Purpura
Rare complication
Rapid onset of thrombocytopenia as a result of
anamnestic production of platelet
alloantibody
Usually occurs in multiparous woman

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Posttransfusion Purpura
Pathophysiology
Platelet Ab (anti-PL ) attach platelet
A1


surface  destruction by RES



Signs & Symptoms

Purpura and thrombocytopenia
occur
 ~ 1 – 2 weeks after transfusion

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Posttransfusion Purpura
Therapy and Prevention
Get expert advise from the
Transfusion Medicine
Department
Corticosteroids combined with
high dose of IVIg
Exchange transfusion

Plasmapheresis

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Bacterial contamination
reaction

Cause gram –ve, gram +ve bacteria
 most frequent – Yersinia enterocolitica


 Pathophysiology
 Bacteria growing in cold temperature


 Produced endotoxin

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Symptoms & Signs
Acute onset within ~ 30 min after
transfusion
Dryness and flushing skin
Fever, hypotension, shaking chills, muscle
pain, vomitting, abdominal cramps, bloody
diarrhea, hemoglobinuria, shock, renal
failure, and DIC.


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Therapy & Prevention
T h e ra p y
Broad – spectrum antibiotics
Symptomatic treatment
Prevention


Ø Phlebotomy and blood components preparation &

processing , thawing by sterile technique.

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Transfusion – Transmitted Diseases
Viral Infections
Hepatitis Viruses :- HBV, HCV
Retroviruses :- HIV

Herpesviruses :- CMV, EBV

Parvovirus :- Human B19 parvovirus

Prion :- infectious particle of CJD

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Transfusion – Transmitted Diseases
Bacterial Infection
Gram negative and positive
Syphilis

Lyme disease (Borrellosis)

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Transfusion – Transmitted Diseases
Parasitic Infections
Malaria
Chagas disease
Toxoplasmosis
Leishmaniasis

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Serological Testing
for Infectious markers

HIV – Ag
Anti – HIV
HBsAg
Anti – HCV
Test for syphilis


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Steps to take when a transfusion
reaction occurs
Stop the transfusion immediately
Leave the needle in the vein and begin infusing
normal saline
Obtain vital signs
Begin O2 if pulmonary symptoms are
prominent
Carry out PE : lung, heart, skin, signs of
abnormal bleeding

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Steps to take when a transfusion
reaction occurs
Obtain a new blood sample for repeat RBC
compatibility test and inspection for
hemolysis
Obtain a urine sample if the patient can
void
Obtain a chest x-ray if pulmonary symptom
are prominent
Make a preliminary assesment of the
situation
Begin definitive treatment

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 Non - Immune - Mediated Hemolysis

Causes
uPhysical
or chemical destruction of
blood: freezing, heating, hemolytic
drug
usolution added to blood
uBacterial contamination
Treatment

–depends on the causes

umildreaction  supportive treatment
usevere reaction  intensive treatment

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Thank you