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Guidelines for Blood Transfusion in Thallassemia Major Patients
Dr.S.Sarfaraz H.Jafry
Husaini Hematology Oncology Center
Protocols for Good Bed Side Safe Blood Transfusion Practices in Thallessemia Major
1. Pre transfusion CBC (complete blood counts) must be performed to assess Hb%,, aplastic
crisis and infections before every transfusion. Pre transfusion Hb% should be maintained
between 9 to 10.5g%
2. ELISA screened (HBV, HCV, HIV, SYPIHILIS & MALARIA); Leukocyte poor Red
cell concentrate is recommended instead of whole blood transfusion.
3. Washed red cells are recommended for those patients only who experience repeated
severe allergic transfusion reactions.
4. Blood to be transfused must be collected within a week’s time.(Can be extended to two
week’s time, if the blood bag contain nutrient / additives such as SAGM and AS-3)
5. Blood grouping and cross matching must be performed on every unit to be transfused by
WHO recommended procedures.
6. Transfusion with ABO and Rh (D) compatible Blood is a mandatory recommendation
7. Blood bags must be checked and counter checked by the transfusionist and the doctor in
charge respectively prior to transfusion for donor & recipient groups, cross match
compatibility, unit number, screening, temperature and the right recipient
8. Time interval between two transfusions ranges from two to five weeks taking into
account patient’s work, school schedule, pre transfusion Hb% and clinical condition. This
regimen ensures normal physical activities, normal growth, adequate bone marrow
suppression and low iron deposition.
The recommended volume of red cell transfusion is influenced by the use of
different anticoagulant/additive solutions, age, weight, Hb%, the clinical
condition of the patient & the target level of hemoglobin. Generally the
recommendations are 10 – 15ml/kg(based on 75% hematocrit of donor’s RBCs)
or one to two units in terms of number of units per day.
9. Blood transfusion must be completed within four hours time depending upon weight,
Hb%, clinical condition of the recipient and the quantity of blood to be transfused
Dr.S.Sarfaraz H.Jafry
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10. Blood pressure, temperature, pulse and respiration must be recorded before, during and
after the transfusion.
11. Extended red cell antigen typing only once (preferably before putting patients on
transfusion therapy) and the Antibody screening before every transfusion to detect
new antibodies of all the registered patients, then donor selection accordingly
must be an important aspect of protocols
12. Blood transfusions of units donated by 1st degree relatives should be avoided because
that might affect the outcome of a later bone marrow transplantation due to the risk of
antibodies development
Measure of effectiveness of blood transfusion
13. Rate of fall in Hb% should not exceed 1g/dl/week in splenectomised patients &
1.5g/dl/week in non splenectomised patients
14. If fall in Hb% is at a greater rate then watch for:
1. Alloimmunisation
2. Hypersplenism
3. Poor quality blood
4. Infection related hemolysis
5. Drug induced hemolysis
6. Bleeding
Blood transfusion services ; (a quality blood product)
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To safeguard the health of the transfusion recipient, including patients with thalassaemia,
blood should be obtained from carefully selected regular voluntary, non-remunerated
donors and should be collected, processed, stored and distributed, in the context of
dedicated, quality assured national blood transfusion centres.
Nationally developed legislation-based on EU, Council of Europe, North American,
World Health Organisation (WHO) or other international directives, recommendations or
relevant laws and taking into account national needs, resources and prevalence of
infectious agents, should safeguard the quality of blood transfusion services. Blood
donation practices, donor selection (e.g., through questionnaire) and product screening
constitute some of the most important strategies that contribute to the safety and
adequacy of blood
Transfusion Therapy in Thalassaemia
Five of the most common questions related to the transfusion therapy of patients with
thalassaemia major:
1.
2.
3.
4.
When to initiate transfusion therapy and whom to transfuse;
How blood is processed for effective and safe transfusion therapy in thalassaemia major;
Is there an optimal haemoglobin (Hb) level for effective transfusion;
Do transfusion requirements affect the success of iron chelation therapy;
Dr.S.Sarfaraz H.Jafry
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5. What are the most serious transfusion related (TR) reactions (common and less frequent);
Decision for blood transfusion whom,
The following should be included in the investigations:
1. Confirmed laboratory diagnosis of thalassaemia major;
2. Laboratory criteria:Hb < 7g/dl on 2 occasions, > 2 weeks apart (excluding all other
contributory causes such as infections) or
3. Laboratory and clinical criteria, including:Hb > 7g/dl with:-Facial changes, Poor growth,Fractures, and-Extramedullary haematopoiesis
Adverse Reactions of Leucocytes
•FNHTR
•HLA allo-immunization
•TRALI
•GVHD
•Transfusion related immune suppression
•Transfusion transmissible viral infection
–CMV - EBV
–HTLV - HIV
Leucodepleted packed red cells.
Patients with β-thalassaemia major should receive leucoreduced packed red blood cells with a
minimum haemoglobin content of 40g.
Reduction to 1 × 106 or less leucocytes per unit (mean counts as low as 0.05 × 106 are
achievable) (Council of Europe, RE 2006) is considered the critical threshold for
eliminating adverse reactions attributed to contaminating white cells
Leucocytes reduction
•Reduces risk of HLA allo-immunization (leucocytes < than 5x106)
•Reduces risk of transmission of Leucotropic viruses (< than 5x106)
•Reduces risk of FNHTR due to donor cytokine (5x108 , if pre-storage)
•Reduces risk of FNHTR due to reaction against donor WBCs (5x108)
Methods Of Leuco-depletion
•Concept was brought by Fleming in 1920s
•Pre Storage: Carried out in blood banks during blood collection or shortly after collection
•During Storage: Carried out in blood banks before issue
•Post Storage: Carried out at patient bed side
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Freezing, Deglycerolizing and Saline Washing (Rare)
•After WB collection buffy coat can be removed to 1.9 x 106 after freezing and de-lycerolization
•These red cells can be given to IgA deficient and PNH patients
Leuco-depleted blood
•Shelf Life: 24 hours when stored at 40C
Centrifugation Technique
•After blood collection (Top-and-Bottom Bags)
•Bag are processed to Hard Spin to obtain Plasma, Buffy Coat and RCC layer
•From Bottom RCCs are removed and from Top Plasma is removed
•These RCC contains 70-80% less leucocytes than un-modified RCCs to prevent FNHTR
•Primary bag is left with Buffy coat & platelets
Centrifugation Top & Bottom Bag
Pre Storage Leukocyte
Filters In-Line Filter bag attached to RCC Bag
Dr.S.Sarfaraz H.Jafry
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Centrifugation Technique
•After blood collection (Top-and-Bottom Bags)
•Bag are processed to Hard Spin to obtain Plasma, Buffy Coat and RCC layer
•From Bottom RCCs are removed and from Top Plasma is removed
•These RCC contains 70-80% less leucocytes than un-modified RCCs to prevent FNHTR
•Primary bag is left with Buffy coat & platelets
Than, these bags are pooled usually 4-6
•SOFT spin is done with the addition of Plasma OR Additive solution to prepare pooled platelets
•Leucocytes are discarded
•Loss of some Red Cells & Platelets are seen with this technique
Saline Wash Leuco-depleted RCC
Less commonly adopted
Washing of stored red cell concentrate with cold saline can remove leucocytes (buffy coat) and
plasma
Saline Wash Leuco-depletion prevents FNHTR & allergic reactions
Filtration
Pre-Storage Filtration
In-Line Leucocyte filtration produces <5x106 WBCs reduced Products with normal shelf life (35
days) and meet 85% retention of original RBCs
Today a single filter provide Leuco-reduced
RCCs, Platelets and FFP from a Whole Blood
Washed red Packed Cells for repeated transfusion reactions
Washed red cells may be beneficial for patients with thalassaemia who have repeated severe
allergic transfusion reactions. Saline washing of the donor product removes plasma proteins that
constitute the target of antibodies in the recipient. Other clinical states that may require washed
red cell products include immunoglobulin A (IgA) deficiency, in which the recipient’s preformed
antibody to IgA may result in an anaphylactic reaction. Washing usually does not result in
adequate leucocyte reduction and should not be used as a substitute for leucoreduction. Instead,
washing should be used in conjunction with filtration. In addition, washing of red cell units may
remove some erythrocytes from the transfusion product, and it is therefore valuable to monitor
post-transfusion haemoglobin levels to ensure attainment of the targeted Hb level.
Dr.S.Sarfaraz H.Jafry
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Cell washing procedure
1.. Dispense 4-5 drops of whole blood or packed red cells in a 4 cc tube.
2. Fill the tube ¾ full with 0.9% saline to resuspend the cells.
3. Centrifuge the tubes for 2 to 3 minutes at 3400 rpm.
4. Discard maximum supernatant fluid/saline by a plastic dropper.
5. Repeat this washing procedure three times, every time save red cells sediment.
6.. Deposit at the bottom of the tube is washed cells
Development of new antibodies (Allo-immunization)
Development of one or more specific red cell antibodies (alloimmunisation) is a common
complication of chronic transfusion therapy. Thus it is important to monitor patients carefully for
the development of new antibodies and to eliminate donors with the corresponding antigens.
Anti-E, anti-C and anti-Kell alloantibodies are the most common. However, 5–10% of patients
present with alloantibodies against rare erythrocyte antigens or with warm or cold antibodies of
unidentified specificity.
It is recommended that:
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
Before embarking on transfusion therapy, patients should have extended red cell antigen
typing that includes at least C, c, E, e and Kell, in order to help identify and characterise
antibodies in case of later immunisation;
All patients with thalassaemia should be transfused with ABO and Rh(D) compatible
blood.
In addition, the use of blood that is also matched for the C, E and Kell antigens is highly
recommended in order to avoid alloimmunisation against these antigens. Some centres
use even more extended antigen matching.

Before each transfusion it is necessary to perform a full crossmatch and screen for new
antibodies.
If new antibodies appear, they must be identified so that in future blood lacking the
corresponding antigen(s) can be used. A complete and detailed record of antigen typing,
red cell antibodies and transfusion reactions should be maintained for each patient, and
should be readily available when and if the patient is transfused at a different centre.
Transfusion of blood from first-degree relatives should be avoided because of the risk of
developing antibodies that might adversely affect the outcome of a later stem cell
transplant.
Dr.S.Sarfaraz H.Jafry
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Complications and side effects;
The repeated blood transfusions have dangers and side effects like iron overload and contraction
of transfusion-transmitted infections (TTI) such as HIV (with risk to evolve into
AIDS),HBsAg,and HCV (with high risk of developing chronic hepatitis,liver cirrhosis and
hepatocellular carcinoma),whose risks increases with the age of child and number of red cell
transfusions done.
The risk of TTI has been cut down thanks to the screening immunodeficiency virus and
hepatitis;anyway new events like West Nile Virus and babesiosis,which are not always screened
for,may be in the the blood from asymptomatic donors.
When a pre transfusion Hb level > 9-10 g/dL is obtained,then the transfusions are given every
month in the first years of age and then every 2-to-4 week. It usually starts in the first 2 years of
age.
Hepatitis B vaccination is given before starting the transfusion treatment,as is hepatitis A vaccine
when the child has the right age to do it.
Careful donor selection and screening – voluntary, regular non-remunerated blood
donation.
Screening of all blood donations should be mandatory for the following
infections and using the following markers:

HIV-1 and HIV-2: screening for either a combination of HIV antigen-antibody or HIV
ntibodies
 Hepatitis B: screening for hepatitis B surface antigen (HBsAg)
 Hepatitis C: screening for either a combination of HCV antigenantibody or HCV
antibodies
 Syphilis (Treponema pallidum): screening for specific treponemal antibodies.
 Malaria screening must be done against all specific agents (vivax,falciparum& oval)
5 Screening of donations for other infections, such as those causing malaria
6 Where feasible, blood screening should be consolidated in strategically located facilities at
national and/or regional levels to achieve uniformity of standards, increased safety and
economies of scale.
7 Adequate resources should be made available for the consistent and reliable screening of blood
donations for transfusion-transmissible infections.
8 A sufficient number of qualified and trained staff should be available for the blood screening
programme.
9 There should be a national system for the evaluation, selection and validation of all assays used
for blood screening.
10 The minimum evaluated sensitivity and specificity levels of all assays used for blood
Screening should be as high as possible and preferably not less than 99.5%.
Dr.S.Sarfaraz H.Jafry
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11 Quality-assured screening of all donations using serology should be in place before screening
strategies utilizing nucleic acid testing are considered.
Laboratory testing for screening of blood against TTI.
Various types of assay have been developed for use in blood screening over the past three
decades. The assays most commonly in use are designed to detect antibodies, antigens or the
nucleic acid of the infectious agent. However, not all assays are suitable in all situations and each
assay has its limitations which need to be understood and taken into consideration when selecting
assays.
The main types of assay used for blood screening are:
Immunoassays (IAs):
— Enzyme immunoassays (EIAs)
— Chemiluminescent immunoassays (CLIAs)
— Haemagglutination (HA)/particle agglutination (PA) assays
— Rapid/simple single-use assays (rapid tests)
Nucleic acid amplification technology (NAT) assays.
In the context of blood screening, appropriate evaluation is required in selecting the type of assay
for each TTI, based on critical assay characteristics, such as sensitivity and specificity, as well as
cost and ease of use.
Clinical record
To calculate the the annual blood requirements,it is necessary to keep track each time of the
pretransfusion Hb level,the transfused blood,including the volume given and the haematocrit,and
the child’s weight.
Blood Safety
It is very important that the transfused blood is of high quality,and the best donors have to be
screened and chosen among regular voluntary,non-remunerated donors;it should be gathered and
stored in a blood transfusion center.
Transfusion Reaction; They are categorized as follows with sign, sympto,, possibl cause &
immediate management;
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Category 1: Mild Reactions
Signs
Symptoms
Urticaria /
rash
Pruritis
(itching)
Possible
Cause
Immediate Management
Allergic
1. Stop transfusion
2. Assess patient
3. An antihistamine may be required
4. Transfusion may be restarted if no other
signs/symptoms are present
5. If signs/symptoms worsen treat as Category 2.
Category 2: Moderately severe reactions
Signs
Symptoms
Possible cause
Immediate Management
Flushing
Anxiety
Allergic (moderatelysevere)
1. Stop transfusion and maintain IV line with
N. Saline
Urticaria
Pruritis
Palpitations
Fever
Mild
dyspnoea
Febrile non-haemolytic
transfusion reaction:antibodies to white cells
or
2. Contact Medical Officer
Rigors
Platelets antibodies to
proteins including IgA
possible contamination
with pyrogens and / or
bacteria
4. Further investigation and management
according to clinical features
Restlessness
Headache
Tachycardia
Dr.S.Sarfaraz H.Jafry
3. Patient may require antihistamine and / or
paracetamol
5. If investigation required: complete
Transfusion Reaction Form and send
blood pack, form and samples to blood
bank
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Category 3: Life threatening reactions
Signs
Symptoms Possible cause
Immediate Management
Rigors
Anxiety
1.
Stop transfusion and maintain IV line with N.
.Saline
Fever
Chest pain
Acute intravascular
haemolysis (wrong
blood)
2.
Contact Medical Officer
Restlessness
Pain at
infusion
site
Bacterial
contamination
and septic shock
3.
Respiratory
distress
Fluid overload
Manage immediate needs:
i. Fluid for hypotension
ii. Oxygen
iii. Adrenaline for anaphylaxis
iv. Diuretic for fluid overload
4.
Complete Transfusion Reaction Form and
send blood pack, form and samples to blood
bank
Hypotension
Tachycardia
Dark Urine
Unexplained
bleeding
(DIC)
Anaphylaxis
Loin/back
pain
Headache
Transfusion related
acute
lung injury (TRALI)
Further management according to likely cause
Dyspnoea
Hemovigillance
Hemovigillance is a process of collection of data of all adverse reaction of blood in a transfusion
centre . A set of surveillance procedure intended to collect and asses information on unexpected
or undesirable effects resulting from transfusion of blood products, in order to prevent there
occurrence and recurrence.
Why Need Haemovigilance
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•
•
•
Error is an inherent component and an intrinsic by-product of every activity in which humans are
involved
Transfusion errors probably existed once blood transfusion became an essential component of
medical treatment
Errors and adverse events carry a high financial burden
Many transfusion errors can be benign but may be pointers to a careful re-assessment of the
process
Dr.S.Sarfaraz H.Jafry
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•
•
However, the systematic acknowledgement, recognition and analysis of these errors are certainly
a much more recent phenomenon
Sufficient detail to make effective recommendations for improved practices
Focus on improved safely and outcomes
Haemovigilance Information
Merits of Hemovigilance
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Haemovigilance data can be used to define priorities for blood transfusion
Improve public confidence and trust.
Improve the quality of Transfusion Service.
Understanding of frequency and range of transfusion related events.
Supply information to the medical community regarding the risks related to transfusion
Taking corrective measures to prevent or minimize incidences
Incomplete reporting
Detection of transfusion relationship of late events, including infections
Limited details
Variation in terminology and definitions
Influence of health care system’s or institution’s culture regarding compliance, process
improvement and reporting
Any transfusion related adverse event (including near misses) occurring in a patient is reported to
the Hospital Blood Bank (HBB) by the ward
(Transfusion related adverse event form)
Serological investigation is done in the HBB
Feedback is sent to the ward
All these incidences have to be reported by the HBB at the end of each month to the
corresponding BTA.
Dr.S.Sarfaraz H.Jafry
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Transfusion Committees;
It is highly recommende to stablish a transfusion committee I a Transfusion center
,committee should be comprises by the following members;
1.Transfusion physician
2.Hematologist/Pathologist
3.Blood Bank Officer
4.Quality Control Manager of blood bank
5. Sr.Nursing staff of the Technician
Scope of functions of transfusion committee should be as follows
•
•
•
•
•
Quality Management and Quality Tools
Transfusion Reaction Oversight
Role in Blood Management
Transfusion Guidelines
Implementation and Management
Summarized Recommendation for safe blood transfusion in
Thallassemia Major Patients
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Careful donor selection and screening – voluntary, regular non-remunerated blood
donation.
Confirm diagnosis of thalassaemia major.
Before initiation of transfusion therapy, confirm laboratory and clinical criteria.
Before first transfusion, extended red cell antigen typing of patients at least for C, E and
Kell.
At each transfusion, give ABO, Rh(D) compatible blood. Matching for C, E and Kell
antigen is recommended.
Before each transfusion, full cross-match and screen for new antibodies.
Keep record of red cell antibodies, transfusion reactions and annual transfusion
requirements for each patient.
Use leucoreduced packed red cells. Pre-storage filtration is recommended, but blood bank
pre-transfusion or bedside filtrations are acceptable alternatives.
Washed red cells for patients who have severe allergic reactions.
Use red cells stored in CPD-A, as fresh as possible (less than one week old) and in
additive solutions for less than 2 weeks.
Transfuse every 2–5 weeks, maintaining pre-transfusion Hb above 9–10.5 g/dl, but higher
levels (11–12 g/dl) may be necessary for patients with heart complications.
Dr.S.Sarfaraz H.Jafry
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Dr.S.Sarfaraz H.Jafry
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