EMI A SO

SS

CI
THAL

ETY
M S
AU
RITIU

THALASSEMIA
SOCIETY OF MAURITIUS

STANDARD PROTOCOLS
& GUIDELINES
FOR
MANAGEMENT OF PATIENTS
WITH THALASSEMIA

With the collaboration of

Ministry
& of Health &
Wellness

UPDATED VERSION - MAY 2022

 STANDARD
PROTOCOLS & GUIDELINES
FOR
MANAGEMENT OF PATIENTS
WITH
THALASSEMIA
EM I A SO
SS
A

CI
THAL

ETY
M S
AU
RITIU

Thalassemia Society of Mauritius

With the collaboration of

&
Ministry of Health and Wellness

REPUBLIC OF MAURITIUS
UPDATED VERSION ­ May 2022

Official Launch 01.06.2022

 We would like to express our deepest thanks to the following
medical experts (in alphabetical order) who have contributed to the
review and updating of these Standards, with the coordination and
support of the Thalassemia International Federation (TIF) and also
to our local collaborators as mentioned below:

Prof. Antonio Piga, Professor of Paediatrics, Dean of the Medical

School of the University of Torino, Head of the Division of Pediatrics
and Thalassemia Centre of the S. Luigi University Hospital of
Orbassano, Torino, Italy.

Dr Dimitris Farmakis, Consultant Cardiologist, Associate Professor

of the Medical School of the University of Cyprus, Attending
Cardiologist, University of Athens Medical School, First Department
of Internal Medicine.

Laiko Hospital, Second Department of Cardiology, Attikon Hospital,

Athens, Greece.

Dr Michael Angastiniotis, Paediatrician, Former Director of the

Thalassaemia Centre and Paediatrics Department of the Arch.
Makarios Hospital, Nicosia, Cyprus.

Dr Mohammed Naveed, Consultant Geneticist, Fujairah Hospital,

UAE Ministry of Health, Fujairah, United Arab Emirates.
ii
Local Collaborators are as follows :

Dr Mrs. Janaki Sonoo – Consultant Pathologist, Head of National

Blood Transfusion Service, Director of the Central Lab, Founder
Member/Managing Commitee Member of the Society.

Dr. Mrs. Nasseema Aumeer ­ Consultant Paediatrics J. Nehru Hospital

Dr. Leeraj Ramdani – Community Physician at Dr A.G. Jeetoo Hospital,

Vice President of the Society.

Dr. Dooshanveer Chowbay Nuckchaddy – Specialist in Internal

Medicine and Infectious Diseases at Dr A. G. Jeetoo Hospital.

Ms Sabina Moideen Saib – Charge Nurse at Thalassemia Day Care

Ward at J. Nehru Hospital.

iii
 Preface

Thalassemia is a heterogeneous group of haemoglobin disorders

due to a decreased or absent production of normal globin chains.
They are the most common recessive diseases worldwide, with an
estimation of 1–5% of the global population carriers of a genetic
Thalassemia mutation. The thalassemias are most frequent in south­
eastern and southern Asia, in the Middle East, in the Mediterranean
countries, and in North and Central Africa; however, in view of
continued migration, thalassemias are now also becoming increasingly
common in North Europe and North America. These changes have
challenged health professionals and policymakers throughout the
region in providing equitable access to quality services for prevention,
diagnosis and adequate treatment of thalassemias.

In Mauritius, it is estimated that there are around 250 patients with

Transfusion Dependent Thalassemia (TDT). Majority of these are over
the age of 15 years. At the time of publishing of this report, in the
Republic of Mauritius there is no specialized unit for managing these
patients. Currently the management of Thalassemia is being done in
various regional hospitals and private health institutions. In the absence
of a dedicated Thalassemia treatment Center, with a clinical hematologist
trained in this subspecialty, the treatment and management of
Thalassemia remains quite varied from hospital to hospital.
iv
 An effort has been made to publish this protocol to guide the
healthcare practitioners in adhering to the best practices in the care
and management of Thalassemia patients. This is a comprehensive
coverage of practical aspects of management of Thalassemia patients.

The readers are referred to the official Thalassemia International

Federation (TIF) publications for more details. These TIF publications
can also be downloaded from TIF website at:

https://thalassaemia.org.cy/publications/tif­publications/

v
 Table of Contents
Genetics, Pathophysiology and Diagnosis of Thalassemia ................1
Transfusion Dependent Thalassemia (Thalassemia Major)...............4
Diagnosis of Thalassemia Major .......................................................4
Confirmation of Beta thalassemia major: .........................................5
Goals of Transfusion Therapy:...........................................................5
Precautions before starting regular blood transfusions:...................6
Investigations before First Blood Transfusion: ..................................6
Type of Blood (Red Cell Component): ...............................................7
Preparation before starting blood transfusion:.................................8
Pre­Transfusion Process: ...................................................................9
Checking of Compatibility: ................................................................9
Blood Calculation Formula:.............................................................10
Blood Transfusion process: .............................................................10
Flow Rate and blood volume transfused: .......................................11
The desired level of Hemoglobin: ...................................................13
Interval between blood transfusions: .............................................14
Assessing Transfusion Efficiency: ....................................................14
Post Transfusion: .............................................................................14
Transfusion record to be kept for each patient:..............................15
Non­transfusion­dependent thalassemia .......................................16
Definition of NTDT ..........................................................................16
Types of NTDT: ................................................................................16
Diagnosis of NTDT ...........................................................................16
Indications for giving occasional blood transfusions in NTDT: ........17
Indications for giving regular blood transfusions in NTDT:..............17

vi
Transfusion Interval in NTDT: ..........................................................18
Transfusion record in NTDT: ............................................................18
Practical Recommendations in NTDT: .............................................18
Iron Load ­ Monitoring and Treatment ...........................................19
Importance of Iron Chelation:.........................................................19
Estimation of Iron overload ............................................................19
Time to start Iron Chelation ............................................................20
Iron Chelation Medications:............................................................20
Desferrioxamine (DFO)...................................................................21
Deferiprone .....................................................................................23
Deferasirox ......................................................................................25
Iron Chelation initiation: .................................................................25
Monitoring during Iron Chelation: ..................................................26
Chelation Therapy in previously untreated patients
(above 2 years of Age).....................................................................26
Chelation Therapy in Patients with HIGH iron stores......................27
Chelation Therapy in Patients with increased risk of
Cardiac Disease &/or Diabetes Mellitus...............................................27
Chelation Therapy in Patients with satisfactory iron stores............29
Long term care & other management: ...........................................29
Nutrition & Diet ..............................................................................30
Psycho­social Issues ........................................................................30
Consideration For Referral For Bone Marrow Transplantation .......30
Surgery in Thalassemia patients .....................................................31
Splenectomy in Thalassemia patients .............................................31
Vaccines Pre & Post Splenectomy Table..........................................33
Routine Immunisation in Thalassemia Patients ..............................34

vii
Hepatitis­B Vaccination for Thalassemia patients...........................35
Hepatitis­A Vaccination...................................................................36
Transition from Pediatric Care and Management of Adults............37
Prevention and management of Cardiac Complications.................37
Prevention and management of Endocrine Complications.............37
Prevention and management of Liver Complications .....................38
Prevention and management of Bone Complications ....................38
Counselling......................................................................................39
Thalassemia minor / carrier ............................................................39
Clinical picture.................................................................................39
Lab Investigation .............................................................................40
Objectives of diagnosing carriers ....................................................40
COVID 19 and Thalassemia Patients ...............................................41

References:

1. TIF Guidelines for management of TDP.

2. Trust Guideline for Patients with an Absent or Dysfunctional
Spleen NHS Norfolk and Norwich University Hospitals –
NHS Foundation ­ Date approved 01/04/2020

Are also attached:

1. Checklist for monthly, quarterly, yearly, biennial medical
assessment
2. Notes relating to Covid­ 19 Pandemic
3. Iron toxicity chart
viii
1. Genetics, Pathophysiology and
Diagnosis of Thalassemia
1.1 Thalassemias are group of blood diseases characterized by
decreased or absent synthesis of normal globin chains of
Hemoglobin molecule. Normal adult hemoglobin molecule
comprises of two α and two β globin chains. Other types of globin
chains which are present are γ and δ. According to the globin
chains involved, Thalassemias are called α, β, γ, δ, δβ or γδβ

1.2 Phenotypic classification

1.3 This is based on clinical severity and transfusion requirements.

1. Thalassemia Minor/Trait
2. Thalassemia Intermedia
3. Thalassemia Major

NTDTs - Non Transfusion Dependent Thalassemias (Thalassemia)

Transfusion Occasional Intermittent Regular lifelong

seldom required transfusion transfusion transfusion

Ƚ Thalassemia Trait Mild HbE/ Ⱦ Moderate HbE/ Ⱦ Non Deletional Hb H

Ⱦ Thalassemia Trait Thalassemia Thalassemia Ⱦ Thalassemia Major

HbC/ Ⱦ Deletional Hb H Severe HbE/ Ⱦ

Thalassemia Thalassemia Thalassemia

TDTs : Transfusion Dependent Thalassemia

1
Pathophysiology

Basic defect in B thalassemia is a decrease or absence of βchain

synthesis with relative excess of α chains. This leads to
• Decrease in hemoglobin
• Ineffective erythropoiesis
• Hemolysis

Ineffective erythropoiesis leads to increased erythropoietin

secretion which causes marked bone marrow erythroid
hyperplasia leading to :
• Skeletal deformities
• Osteoporosis
• Extramedullary masses (hematopoiesis)

Anemia causes
• Retarded growth
• Cardiomegaly and cardiac failure

Increased of red cells in peripheral circulation contributes to

splenomegaly

Ineffective erythropoiesis also leads to increased intestinal iron

absorption due to deficiency of hepcidin which plays a major role
in iron homeostasis.
2
 Effects of excess production of free α globin chains in β
thalassemia

Reduced levels of Ⱦ Absence of Ⱦ

globin chains (Ⱦ+) globin chains (Ⱦͼ)
Excess free Ƚ globin chains

Membrane damage to Precipitation within erythroid precursors

peripheral erythrocytes within bone marrow

Premature death of erythroid precursors

Hemolysis
Ineffective erytrhopoiesis

Anemia

Erythropoietin
Increased Blood Transfusion
Iron Absorption
Increased

Bone marrow Iron Loading

expansion

Organ failure
Skeletal changes

Hypermetabolic
stage

3
Transfusion Dependent Thalassemia
(Thalassemia Major)

Diagnosis of Thalassemia Major

1.1 Thalassemia major is a Transfusion Dependent state, needing
regular (monthly transfusion) from early infancy.
1.2 Clinical presentation usually occurs between 6 and 24 months of life.
1.3 Persistent and progressive pallor, poor appetite, weakness,
failure to thrive and intercurrent infections are common
symptoms of Thalassemia major.
1.4 Mild jaundice, hemolytic facies (if not adequately transfused)
and enlarged liver and spleen (if not adequately transfused)
are commonly seen during physical examination.
1.5 Characteristically, patients with Thalassemia major have low
Hb <7.0 g/dL (in the absence of any recent febrile illness).
1.6 Patients with Thalassemia major have severe anemia with
MCV <80 fl and MCH <27 pg and peripheral blood smear
showing severe erythrocyte morphologic changes with aniso
poikilocytosis and target cells.
1.7 In the classical form Beta­Thalassemia major, at hemoglobin
analysis, HbA is absent and HbF represents the 92–95% of the
total hemoglobin.
1.8 In other types of Beta­Thalassemia major forms, the HbA
levels can be variable between 10 and 30%; and HbF between
70 and 90%.
4
 1.9 Both parents usually have typical hematological parameters
of beta­thalassemia carriers.

Confirmation of Beta Thalassemia major:

1.1 Hb < 7 g/dl on 2 occasions more than 2 weeks apart with no
other associated stressful conditions (including febrile illness).
1.2 Hb > 7g/dl with facial changes, poor growth, pathological
fractures, extra medullary hematopoiesis.
1.3 Molecular characterization by DNA supporting Thalassemia
Major Diagnosis (Presence of two severe β –Thalassemia
mutations; Absence of readily detectable forms of alpha
Thalassemia; Absence of the Gγ Xmn1cleavage site or other
relevant polymorphisms)

Principle of management of thalassemia major

Goals of Transfusion Therapy:

1.4 Achievement of appropriate hemoglobin level to control
symptoms of anemia and chronic hypoxia, and prevent
1.4.1 Ineffective erythropoiesis,
1.4.2 Secondary bone changes,
1.4.3 Hepatosplenomegaly
1.4.4 Hypervolemia.
1.5 Achieve near normal quality of life
5
Precautions before starting regular blood transfusions:
1.1 The decision to place a thalassemia patient on regular blood
transfusion program for life is rarely urgent; however the
earlier the decision, the better. This observation phase is very
important and its duration is often variable.
1.2 Observe the patient for Hb drop over several weeks and record
lowest Hb reached.
1.3 Observe the patient for signs of ineffective erythropoiesis.
1.4 Observe the patient for signs of growth failure or bone expansion.
1.5 Transfusion should be started promptly when there is
sufficient clinical evidence of severe anemia, failure to thrive,
and/or thalassemic bone deformity.
1.6 Infants and children with a Thalassemia Intermedia phenotype
should be identified and they should not be given transfusion
inappropriately.

Investigations before First Blood Transfusion:

1.1 Complete blood count (CBC)
1.2 Extended blood grouping (if not done earlier) at least for C, E,
and Kell, Coomb’s test
1.3 Liver Function tests
1.4 Serum Calcium and Phosphate
1.5 Urea & Electrolytes
1.6 Hepatitis B Markers including HBsAb titer
1.7 HCV­Ab; if positive HCV­RNA (PCR)
6
 1.8 HIV screening
1.9 Ferritin and iron level
1.10 G6PD screening
1.11 Sickle cell test

Type of Blood (Red Cell Component):

1.1 At each transfusion, give ABO, Rh (D) compatible blood. Red
cell units which are matched for Rh (D, C, c, E, e) and Kell (K)
blood group antigens should be selected.
1.2 CPD­A unit/SAGAM unit which are leukodepleted. Pre­storage
filtration is strongly recommended.
1.3 Hematocrit of CPD­A unit should be approximately 70 and
80%, SAGAM unit approximately 50­65%.
1.4 Transfuse red cells stored in SAGM or CPD­A within 5 days of
collection.
1.5 Large volume units should be chosen, preferably greater than
300 mls (when one or more full unit is required), and
whenever possible units should be less than five days old.
1.6 Cannulation should be undertaken by an experienced nurse
or doctor.
1.7 Transfusions should be planned, and pre arranged with cross
matching unit and given promptly.
1.8 Transfusions should be given on each occasion in a designated
area (Thalassemia Day Care Wards) with suitable facilities,
experienced nurses and a familiar supervising medical team.
7
 1.9 A nurse should be in continuous attendance throughout the
transfusion.

Preparation before starting blood transfusion:

1.1 Check if the patient’s blood transfusion consent is valid. This
should be a yearly written informed consent.
1.2 Ensure that extended blood group, HIV, HBV, HCV and Coomb’s
test are done before 1st transfusion.
1.3 Ensure that HIV, HBV and HCV tests are repeated before
transfusing patients who received recent transfusion outside
the country.
1.4 Send patients’ duly filled cross­matching request form
accompanied by appropriately labelled sample for cross­
matching to the blood bank.
1.5 Ensure that there is no discrepency between the patient
identification on the medical file, blood sample and
crossmatching request form. The minimum identifier should
include patients full name, DOB and hospital unit number and
NID number.
1.6 Confirm with the blood bank, the availability of the blood for
the patient.
1.7 Inform the patient regarding blood availability & reconfirm the
patient’s hospital admission for blood transfusion.

8
Pre­Transfusion Process:
1.1 Assess the patient prior to transfusion and re­inform the
patient about the possible transfusion reactions.
1.2 Verify the doctor’s instructions for blood transfusion.
1.3 Insert IV Cannula and collect blood for investigations.
1.4 While collecting blood from the blood bank, double check the
information on cross matched blood with the Blood Issue Form.
1.5 Transport the cross matched blood in cooler box/bag.

Checking of Compatibility:
1.1 Note the temperature and time on arrival and ensure that the
cooler box temperature was maintained at 2­10°C.
1.2 Check that Cross Match Form details matches with blood bag
details and document same in patient’s folder.
1.2.1 Patient identification (full name & Hospital Record
number),
1.2.2 Blood group,
1.2.3 Donation number of the blood unit
1.2.4 Compatibility status as indicated by blood bank,
1.2.5 Blood bag weight,
1.2.6 Leukodepleted packed red cells,
1.2.7 Collection date
1.2.8 Expiry Date.
1.3 Ensure the blood bag is without leaks, clots, not turbid and
there is no hemolysis.
9
 1.4 Two nurses should verify the blood bag with the cross match
form and sign the form if above mentioned data matches.
1.5 Prime the blood transfusion set with normal saline to check
the patency or any leakage of the set.
1.6 Check Doctor’s instructions and start blood transfusion as per
Standard Precautions.

Blood Calculation Formula:

1.1 If Hb > 8.5 gm/dl:
(13 – Hb) x Weight x 5 = ml to be transfused

1.2 If Hb < 8.5 gm/dl:

Weight x 20 = ml to be transfused

Blood Transfusion process:

1.1 Transfusion should begin as soon as possible after the blood
has arrived in ward.
1.2 Assess the cannula for infusion before starting blood
transfusion and before starting each unit of blood.
1.3 Take the order from the attending physician for flow rate and
amount to be transfused for asymptomatic & symptomatic
cardiac failure patients.
1.4 Any patient exhibiting any cardiovascular symptoms as specified
in the nursing assessment form is to be re­evaluated by
attending physician for flow rate and amount to be transfused.
10
 1.5 Two nurses should countercheck the blood bag again with the
transfusion requisition and the I.D Band at the bedside, prior
to commencing the transfusion.
1.6 Ask the patient to state his/her full name. If there is any
discrepancy or the patient condition doesn’t allow for
transfusion, return the blood bag to the blood bank within 30
minutes.
1.7 Transfuse blood using the infusion pump.
1.8 Do not interrupt a transfusion but let it go to completion. If
interruption is absolutely necessary, in case of reaction or any
other complaint, stop the blood transfusion or, if needed, run
0.9 % saline at a slow drip to keep the vein open as per
physician order.
1.9 Observe that blood that has been stopped can be restarted
within 30 minutes as per the attending physician order, which
should finish within 3 hrs.(Maximum within 4 hours from the
time of blood collection from the blood bank).
1.10 Supervise the patient if they are moving around with blood on
flow, patient is not allowed to leave the ward frontier.
1.11 The second unit of blood may be given in a 30 minutes of interval.

Flow Rate and blood volume transfused:

1.1 Flow Rates: If there is no history of cardiac failure/ Hb > 7 gm/ dl
1.1.1 Administer blood SLOWLY for the first 15 minutes
at 2­3ml/kg/hr (80­120ml/hr).
11
 1.1.2 If there is no reaction in first 15 minutes, flow rate
can be increased to 4­5 ml/kg/hr; (150­200 ml/hr)
1.1.3 The recommended volume should not exceed
20ml /kg/visit for adult patients.
1.1.4 The recommended volume should not exceed
15ml/kg /visit for pediatric patients.
1.1.5 The recommended volume should not exceed
1200 ml per visit.
1.1.6 The recommended flow rate is 5 ml/Kg/hr if the
patient is < 40 Kg.
1.1.7 The recommended maximum flow rate is 200
ml/hr for patients > 40 Kg.
1.2 Flow Rates: For patients with symptoms of cardiac failure or
symptomatic or asymptomatic severe anemia (Hb <7gm/dl)
and patients with Ejection Fraction (EF) <45% and
asymptomatic):
1.2.1 Administer blood SLOWLY for the first 15 minutes
at 1­2ml/kg/hr (60­80ml/hr)
1.2.2 If there is no reaction in first 15 minutes, flow rate
can be 2­3 ml/kg/hr
1.2.3 For patients with EF < 45% and asymptomatic, or
asymptomatic severe anemia (Hb less than 7
grams) or has history of cardiac decompensation,
the recommended flow rate is 2­3 ml / Kg/ hour
with a maximum of 15ml /kg/visit.
12
 1.2.4 For patients with symptoms of cardiac failure or
symptomatic severe anemia, the recommended
flow rate is 2ml / Kg per hour with a maximum of
12ml /kg/visit in addition to Furosemide
intravenously prior to commencing the transfusion
as advised by the physician.
1.3 Transfuse exact calculated amount for children and patients
diagnosed with cardiac problems using blood transfusion
burette.
1.4 Blood for adult patients is to be rounded to the nearest one
bag volume.
1.5 If patient’s blood requirement is more than the above, then
further appointments are to be planned and arranged as
needed. For example if a blood bag has 200 ml of blood and
patient request is for 275 ml then transfuse 1bag only (200 ml)
and schedule an earlier appointment instead of using another
bag where most blood will be wasted

The desired level of Hemoglobin:

1.1 Pre transfusion hemoglobin level should be between 9 ­10.5 g/dL.
1.2 If Pre transfusion Hb is 8.5 and above, Hb is to be raised to 13 g/dL.
1.3 If Pre transfusion Hb is 8.5 and less, Hb is to be raised by 4 grams.
1.4 The increment in Hb should not exceed 5 g/dL per visit.

13
Interval between blood transfusions:
1.1 Lifelong regular blood transfusions are usually administered every
2 to 4 weeks, to maintain a pre­transfusion hemoglobin level of Hb
9.0 ­ 10.5 g/dl and mean annual pre­transfusion Hb of > 9.5 g/dL.
1.2 For patients with cardiac failure try to maintain pre­
transfusion hemoglobin levels more than 10 g/dL through
frequent transfusions.

Assessing Transfusion Efficiency:

1.1 Pre transfusion­ Hb: ≥ 9.0 g/dl; and Post­Hb should not be
greater than 13 g/dl.
1.2 Mean annual pre­transfusion Hb >9.5 g/dl.
1.3 Post­ transfusion Hb should be determined, only if indicated.
1.3.1 To evaluate the degree of hypersplenism.
1.3.2 To evaluate unexplained changes in response to
transfusion

Post Transfusion:
1.1 Check vital signs prior to, during and after transfusion.
1.2 Notify the physician for any changes in the vital signs or if
patient develops new symptoms.
1.3 Document the procedure, vital signs, and reaction if any,
along with nurses notes.
1.4 After completion of the transfusion document the time the
transfusion ended and the amount of blood that was transfused.
14
 1.5 Collect Post transfusion Hb, only if indicated and this should
be done only after 30 minutes of transfusion, from another
fresh IV line.
1.6 Continue monitoring the patient for 1 hour post transfusion.
1.7 Inform the patient about the possible delayed transfusion
reactions and what to do in case he/she develops such a
reaction and how to seek help from the nearest clinic/ hospital.
1.8 Collect a sample of the remnant of the blood bag, label it with
the patient identification and donor number in an EDTA tube
and store this sample in a refrigerator at 4 degree centigrade
and this can be discarded 48 hours later if no adverse reactions
are reported within this time.
1.9 Fill the blood reaction form, if there is a reaction.

Transfusion record to be kept for each patient:

1.1 Pre transfusion Hb,
1.2 Volume of blood transfused,
1.3 Weight of patient,
1.4 Antigen typing, red cell antibodies,
1.5 Any transfusion reactions,
1.6 Annual Packed Red Cells consumption in ml/kg of body
weight/year should be calculated and recorded when
evaluating a state of increased blood consumption.
1.7 Development of any auto or alloantibodies.

15
Non­Transfusion­Dependent Thalassemia

Definition of NTDT
1.1 NTDT are those patients who do not require regular lifelong
transfusions for survival, although they may require occasional
or even frequent transfusions in certain clinical settings and
for defined periods of time.

Types of NTDT:
1.1 β­thalassemia Intermedia,
1.2 Hemoglobin E/β­thalassemia (mild and moderate forms),
1.3 α­thalassemia Intermedia (HbH disease)

Diagnosis of NTDT
1.1 This should be suspected in patients who present at a later age
with similar but milder clinical findings than thalassemia major.
1.2 The clinical spectrum of NTDT is very wide as well as the
hematological phenotype.
1.3 Patients with milder forms may have moderate­to­mild
anemia
1.4 The levels of HbA and HbF are very much dependent on the
underlying molecular defects and the degree of ineffective
erythropoiesis.
1.5 These patients are usually capable of surviving without regular
blood transfusions.
16
 1.6 Even in patients with more severe forms of NTDT, Hb levels are
>7 g/dL with drop in hemoglobin occuring when there is
intercurrent infection, surgery or pregnancy.
1.7 Family study, whenever possible, is extremely helpful to
evaluate hematological variations.
1.8 Molecular analysis remains the definitive diagnostic tool for
NTDT

Indications for giving occasional blood transfusions in NTDT:

1.1 Hemoglobin level should not be an indicator for initiation of
transfusion therapy, except in patients with considerably
severe anemia (hemoglobin level frequently < 7 g/dL).
1.2 Occasional blood transfusions should be considered in NTDT
patients within any setting with anticipated acute stress
and/or when there is sudden hemoglobin drop (example:
blood loss, pregnancy, surgery, infections).

Indications for giving regular blood transfusions in NTDT:

1.1 Declining hemoglobin level parallel with enlargement of the
spleen.
1.2 Growth failure (height is more indicative of growth pattern).
1.3 Diminished exercise tolerance.
1.4 Failure of secondary sexual development.
1.5 Delayed bone age.
1.6 Severe bony changes.
17
 1.7 Frequent hemolytic crisis (hemoglobin H disease).
1.8 Poor quality of life.
1.9 Heart disease.

Transfusion Interval in NTDT:

1.1 Lifelong blood transfusions are usually not recommended.
1.2 Maintain a pre­transfusion hemoglobin level of Hb 7 – 9 g/dl.

Transfusion record in NTDT:

1.1 Pre­ transfusion Hb,
1.2 Volume of blood transfused,
1.3 Weight of patient,
1.4 Red cell phenotype, red cell antibodies,
1.5 Any transfusion reactions,
1.6 Annual Packed Red Cells consumption in ml per kg of body
weight / year should be calculated and recorded when
evaluating a state of increased blood consumption,
1.7 Development of auto or alloantibodies.
1.8 Liver and spleen size.

Practical Recommendations in NTDT:

1.1 Patients with NTDT should have their bone age assessed (X­
ray of left hand & wrist) once & then as required.
1.2 NTDT patients should be closely monitored and adequately
managed for iron overload.
18
 1.3 Vaccination against hepatitis B is necessary
1.4 Patients with NTDT should be monitored regularly (refer to
annexed chart) for Growth retardation, Hypogonadism,
Hypothyroidism, Hypoparathyroidism.
1.5 Patients receiving blood transfusions should undergo annual
serologic monitoring.
1.6 Splenectomy should be avoided in NTDT patients younger than
5 years
1.7 A management plan tailored to the individual child must be
agreed and implemented.

Iron Load ­ Monitoring and Treatment

Importance of Iron Chelation:

1.1 In the absence of iron­chelation , patients on regular
transfusions present complications of transfusion­related iron
overload.
1.2 Without iron chelation therapy, heart disease is the major
cause of death; however, hepatic, endocrine and other
complications also occur.

Estimation of Iron overload

1.1 Each ml of red cell contains 1.16 mg iron and an average blood
unit contains 200­250mg iron.
19
 1.2 Patient receiving 15­30 units blood/year receives 3­6 times the
normal annual requirement of 1 gm.
1.3 Serum ferritin reflects iron stones in body and is a good
indicator of iron storage status.
1.4 However Serum ferritin levels are disproportionately increased
in acute inflammatory disorders, infections, chronic liver disease.
1.5 Serum ferritin levels are decreased in presence of vitamin C
deficiency.
1.6 All patients over the age of 10 years should have access to MRI
modalities (Cardiac T2* MRI and either R2 or T2* of liver) for
monitoring myocardial and liver iron.

Time to start Iron Chelation

1.1 Assess serum ferritin levels after 10 – 15 transfusions.
1.2 Initiate chelation therapy when serum ferritin is > 1000 ng/ml.

Iron Chelation Medications:

1.1 Currently three iron chelating agents are available for use in patients
with thalassemia on regular transfusions (Desferrioxamine,
Deferiprone and Deferasirox) providing good results in reducing
cardiac, hepatic and endocrine toxicity due to iron overload.
1.2 The decision to prescribe an iron chelator must consider the
indications and contraindications of each drug and the need
to tailor therapy for each patient.
1.3 A protocol for iron chelation therapy, based on current
20
 published evidence, expert opinion and local conditions
should be used and reviewed at regular intervals.
1.4 Chelation modalities shown to be clinically beneficial include
1.4.1 monotherapy with desferrioxamine or deferiprone
or deferasirox
1.4.2 combination therapy with desferrioxamine +
deferiprone or desferrioxamine + deferasirox.

Desferrioxamine (DFO)
1.1 Common brand name: Desferal
1.2 Route of administration: slow subcutaneous (preferred) or
slow IV infusion.
1.3 Desferal therapy can begin after the first 10­20 transfusions,
or when the ferritin level rises above 1,000 ng/l.
1.4 If chelation therapy begins before 3 years of age, careful
monitoring of growth and bone development is advised.
1.5 Desferrioxamine infusion (SC or IV) should be calculated for
24 hour period.
1.6 Recommended dose: 30­60 mg/kg/day; 5­7 times per week;
1.7 Administer subcutaneous; over 8­ 12 hrs with a specially
designed syringe infusion pump.
1.8 Dissolve 1 vial (0.5 g) of desferal in 2.5­5.0 ml water for injection.
Make the final volume with water to capacity of 10 or 20 ml
syringe fitting in infusion pump and use within 24 hours.
1.9 Sites for subcutaneous Injection include abdominal area (3­
21
 4 inches away from midline of abdomen), Anteromedial thighs
and Triceps area. The choice should be left to the preference
of the patient. Emla cream can be applied 30 mins before
injection.
1.10 Do not mix Desferal in blood bag.
1.11 Desferal can be given at the same time as blood transfusion,
through a separate IV line.
1.12 For IV infusion calculated dose is dissolved in 20 ml of Distilled
water added to 100 ml of Normal Saline. The resulting final
volume of 120 ml should be infused over 8 hours through a
good peripheral vein at a flow rate of 15 ml/hour.
1.13 Ascorbic acid (vitamin C) increases the excretion of iron in
the presence of Desferal. It should be started after the
initial month of desferal therapy. It is given orally in the
dose of 2 to 4 mg/kg per day soon after the start of Desferal
infusion.
1.14 Caution: excessive Vitamin C intake, when Desferal is not given
can cause cardiac toxicity. In patient with cardiac problem the
dose of Vitamin C should not be more than 50 mg.
1.15 At ferritin levels below 1000 ng/L, the dose needs to be
reduced to avoid Desferal related toxicities. Dose reductions
can be guided using the therapeutic index (= mean daily dose
of Desferal (mg per kg)/SF μg/L) and this should be < 0.025
(Porter, 1989).

22
 NOTE : Desferal can be administered at home after adequate
training and education is provided to the
patient/parent
1.16 Monitoring Desferal Toxicity:
1.16.1 Yearly Audiometry
1.16.2 Yearly Eye examination including
electroretinography.
1.16.3 Fever which may suggest septicemia with
organisms such as yersinia, klebsiella. Withold
desferal during fever
1.16.4 Renal function.
1.16.5 In pregnancy avoid desferal if serum ferritin is
between 1000­2000ng/m. If serum ferritin is above
2000ng/ml consider desferal after first trimester.

Deferiprone
1.1 Common brand name: Kelfer; Ferriprox
1.17 Route of administration: Oral
1.18 Dose range: 75 – 100 mg/kg/day in 2­3 divided oral doses.
1.19 If child cannot swallow capsule, open capsule and give
medicine mixed with honey or sugar.
1.20 Common adverse effects:
1.20.1 Nausea, vomiting, diarrhea, abdominal pain and
distension. These mild symptoms often subside on
continuation of therapy.
23
 1.20.2 Arthropathy – 10­20% cases
1.20.3 Agranulocytosis and neutropenia – 1­2% cases,
reversible on discontinuation of therapy.
1.21 Monitoring of patients
1.21.1 Check Hb, total and differential white cell count and
platelet count, weekly for first month and then every
3­4 weeks or when there is sign of infection.
1.21.2 Measure absolute neutrophil count (ANC) before
starting and monitor ANC weekly;
1.21.2.1 If ANC<1.5x109/L stop treatment.
1.21.2.2 If ANC<0.5x 109/L, consider
hospitalization due to risk of sepsis.
1.21.3 Advise patients to report fever, sore throat or any
untoward symptoms.
1.21.4 When there are symptoms of infection or fever
stop medication
1.21.5 Monitor for symptoms of arthropathy
1.21.6 Monitor liver function regularly
1.22 Discontinue Deferiprone, when there is:
1.22.1 Infection
1.22.2 Total Leukocyte Count < 3000 and ANC <1000/ mm3
1.22.3 Platelets < 1,00,000 /mm3
1.23 Do not restart Deferiprone, in case of recurrent leucopenia,
thrombocytopenia or neutropenia.

24
Deferasirox
1.1 Dispersible preparation brands: Exjade, Asunra, Desirox,
Defrijet, Desifer, Oderox
1.2 Non­Dispersible preparation brand: Jadenu
1.3 Route of administration: Oral
1.4 Dose range: 20­40 mg/kg/day; Single dose.
1.5 Dose range of Jadenu: 14­28 mg/kg/day; Single dose.
1.6 Adverse effects: Abdominal pain, loose stools, skin rash,
elevated liver transaminases, elevated BUN, Serum creatinine,
GI bleeding, Metabolic acidosis and mild urinary proteinuria.
1.7 Monitoring of patients
1.7.1 ALT (SGPT)level every week in the first 4 weeks;
and then monthly
1.7.2 Serum Creatinine every week in the first 4 weeks;
and then monthly
1.7.3 Urine Protein/Creatinine ratio every month in the
first 4 months and then quarterly. Proteinuria may
occur occasionally with renal tubular acidosis.
Monitor urine protein regularly.

Iron Chelation initiation:

1.1 Decisions about initiating and changing chelation therapy
should be made by the Thalassemia consultant/specialist,
taking into account the informed preferences of the patient
and carers involved.
25
 1.2 Time should be taken to explain the benefits and possible
adverse effects of each option, using written information in
the appropriate language and health advocacy if required.
1.3 The decision process should be recorded in the patient’s records.

Monitoring during Iron Chelation:

1.1 Patients and carers should be supported in adhering to
chelation therapy using a multidisciplinary team approach,
which includes trained clinicians and nurses, medical social
worker, clinical psychologists etc.
1.2 Compliance and efficacy of medication should be assessed by
monitoring serum ferritin levels every 3­6 months interval, and
any problem should be addressed promptly.
1.3 Patients should be carefully monitored for side effects of iron
chelation therapy.
1.4 All patients should have access to MRI modalities (Cardiac T2*
MRI and either R2 or T2* of liver) for monitoring myocardial
and liver iron.

Chelation Therapy in previously untreated patients

(above 2 years of Age)
1.1 Discuss options and available data with patients/parents.
1.2 1st line: Deferasirox (dispersible preparation) 20­40 mg/kg/day
1.3 2nd line: Desferrioxamine(Desferal) 30­60 mg/kg/day, 5­
6 nights/Week over 10­12 hours
26
Chelation Therapy in Patients with HIGH iron stores
1.1 Patients with High Iron Stores (On treatment)
1.1.1 Serum Ferritin > 2000 ng/ml (increasing trend)
1.1.2 Liver iron > 7 mg/g dry weight by T2* MRI, R2 MRI
1.1.3 Cardiac T2* MRI <15 ms
1.2 When Cardiac T2* MRI available
1.2.1 Increase doses of current chelation drugs to
maximum dose; if tolerated
1.2.2 Consider combination therapy.
1.2.3 Change to Deferasirox if patient has compliance
issues.
1.3 Abnormal ECG/ECHO; but Cardiac T2* MRI not available:
1.3.1 1st line: Chelation should incorporate Deferiprone
either as part of combination or as mono therapy
1.3.2 2nd line: Change to Deferasirox if above regimen
is not tolerated

Chelation Therapy in Patients with increased risk of Cardiac

Disease &/or Diabetes Mellitus
1.1 Patients with increased risk of Cardiac Disease
1.1.1 LV impairment (ejection fraction < 50%, ECHO, or MRI)
1.1.2 Changing ECG patterns, in particular development
of RV strain
1.1.3 Arrhythmias
1.1.4 Severe cardiac loading on T2* MRI (T2*<10ms)
27
 1.2 Discuss options and available data with Patients/parents.
First line:
1.2.1 Deferiprone (75­100 mg/kg/day); as a part of
Combination or Mono therapy
1.2.2 S. Ferritin >2000 ng/ml , Hepatic iron >7mg/g dry
weight
1.2.2.1 Deferrioxamine(desferal) dose
(40mg/kg/day) and Deferiprone dose
(75­100 mg/kg/day);
1.2.3 S. Ferritin 750­2000 ng/ml, hepatic iron 5­7mg/g
dry weight
1.2.3.1 Deferrioxamine (desferal) 20­
30mg/kg/day 3 days a week &
Deferiprone dose (75­100 mg/kg/day);
1.2.3.2 S. Ferritin <750 ng/ml, hepatic iron <5
mg/g dry weight give
1.2.3.3 Deferiprone monotherapy, dose (75­
100 mg/kg/day)

Note: As we do not have the facility for MRI T2* or hepatic iron
monitoring currently, we need to base our management on ferritin
levels and clinical assessment till same is made available.

1.3 If there is discrepancy between hepatic iron status and serum

ferritin levels,consider hepatic iron to guide chelation therapy.
28
 1.4 Second line: (if above regimen is not tolerated or if
neutropenia to Deferiprone)
1.4.1 Deferasirox or Desferrioxamine (desferal)
1.4.1.1 Desferrioxamine 30­40 mg/kg/day,
1.4.1.2 Consider Intravenous Desferrioxamine,
if low LVEF

Chelation Therapy in Patients with satisfactory iron stores

1.1 Continue current regimen.
1.2 Consider reducing dose if using Deferrioxamine (Desferal) or
Deferasirox.
1.3 Offer Deferasirox, if patient requests change after full
discussion or if current regimen not tolerated.

Long term care & other management:

1.1 The child must be monitored closely to determine the likely
clinical course.
1.2 Appropriate information should be given to the family
regarding long term management and outcome with
opportunity for full discussion.
1.3 A management plan tailored to the individual patient must be
agreed and implemented.

29
Nutrition and Diet

Diet
1.1 High calorie, high protein nutritious diet should be taken.
1.2 Limit foods rich in iron such as meat, liver, kidney, egg yolk,
green leafy vegetables,
1.3 Limit preparing food in iron pots.
1.4 Include cereal, bread, milk, soya products to avoid iron absorption.
1.5 Strong green tea/coffee to be taken with meals.
1.6 Avoid taking Vit C, rich citrus fruits along with meals.
1.7 Take milk and milk products frequently
1.8 Referral and regular follow up by a dietician is advised.

Psycho­social Issues
1.1 The psychosocial needs of parents and patients growing up
with Thalassemia must be considered alongside every aspect
of their clinical care.
1.2 Clinical team should include a Clinical Psychologist.

Consideration For Referral For Bone Marrow Transplantation

1.1 Bone Marrow Transplantation is a curative treatment and this
treatment option should be discussed with the familiy at an
early stage, usually before the age of 5 years.
1.2 Bone marrow transplant may be considered if following
criteria are met
30
 1.2.1 HLA matched donor. An HLA matched sibling
donor has better outcome
1.2.2 Patients who are well managed (absence of
hepatomegaly, absence pf hepatic fibrosis and well
compliant to iron chelation)

Surgery in Thalassemia patients

1.1 Surgical procedures requiring general anaesthesia should be
undertaken after consultation with the treating doctor
1.2 Patients should be carefully assessed pre­operatively with
special reference to cardiac, endocrine and metabolic
disturbances which may require correction.

Splenectomy in Thalassemia patients

1.3 Adopt a guarded approach and restrict splenectomy to certain
indications, in view of an increased risk of venous thrombosis,
pulmonary hypertension and overwhelming sepsis after
splenectomy.
1.4 Splenomegaly due to under­transfusion or transfusion
containing low hemoglobin may be reversible.
1.5 Before considering splenectomy in this situation, the patient
should be placed on an adequate transfusion program for
several months and then re­evaluated.
1.6 Splenectomy should be avoided in children <5 years of age because
of a considerably greater risk of fulminant postsplenectomy sepsis.
31
1.7 Indications for splenectomy in thalassaemia major.
1.7.1 Increased blood requirement( annual transfusion
volume above 200­220ml/kg/year ) preventing
adequate control with iron chelation therapy.
However increased transfusion requirements due
to alloimmunization, infections or suboptimal
transfusions should be ruled out.
1.7.2 Evidence of hypersplenism:
1.7.2.1 Packed RBC consumption of more than
250ml/kg/year
1.7.2.2 Presence of leucopenia or
thrombocytopenia
1.7.2.3 Reduced red cell survival (< 15 days) by
chromium studies
1.7.2.4 Radionuclear evidence of splenic
sequestration
1.7.3 Symptomatic Splenomegaly resulting in abdominal
discomfort.

32
 1.8 Patients undergoing splenectomy or having dysfunctional spleen
should be immunized as per table below

VACCINES PRE AND POST SPLENECTOMY

Timing of vaccination
Vaccine Planned Splenectomy Emergency Splenectomy AFTER splenectomy
Start 2 weeks
post splenectomy
Prevenar-13 4 months At least 2 weeks 1 dose
(PCV -13) before splenectomy before splenectomy if notdone
before splenectomy
Pneumovax-23 2 months 2 weeks
(PPSV23) before splenectomy after splenectomy. Every 5 years
6-8 weeks after splenectomy
if PCV -13 done 2 weeks before

33
surgery.
Haemophilus influenzae 4 months At least 2 weeks before splenectomy 1 dose
type B vaccine beforesplenectomy if notdone
(Hib) before splenectomy

Meningococcal ACWY 4 months At least 2 weeks before splenectomy 1 dose

before splenectomy if notdone
before splenectomy

Influenza vaccine Yearly

Prevenar -13 These 3 vaccines can be done at the same time but at different sites.
Hib
Meningococcal ACWY
 1.9 Post splenectomy management
1.9.1 Prolonged penicillin prophylaxis:
1.9.1.1 Penicillin­V 125 mg BD for those below 5
years of age
1.9.1.2 Penicillin­V 250 mg bd for those above
5 years of age for life
1.9.1.3 If allergic to penicillin give
Erythromyecin or Clarithromycin
1.9.2 Give aspirin, if platelet count exceeds 800,000/mm³
1.9.3 Broad spectrum antibiotics for suspected infection
immediately without waiting for laboratory
results.

Routine Immunisation in Thalassemia patients

Routine pediatric immunizations including Prevenar ­13 should be
done as per national schedule. A dose of pneumo 23, pneumococcal
vaccine should be administered at age of 24 months and boosters
considered every 5 years for life.
Patients need to be immunized against hepatitis A and B, especially
patients on chronic transfusions. Individuals who are HIV positive or
undergoing treatment for hepatitis C should not receive live virus vaccines.
Influenza vaccination should be administered yearly.
Vaccination records should be checked and updated annually.
Yearly monitoring of Hepatitis B titters and booster immunizations,
when indicated, will ensure patients are well protected.
34
Hepatitis­B Vaccination for Thalassemia patients
1.1 Thalassemia patients should be regularly monitored for
Hepatitis B immunity.
1.2 All patients are considered immune to HBV if they have a
written documentation of a complete 3 dose HBV vaccine
series and subsequent post vaccination anti­HBs level ≥10
mIU/mL
1.3 Pre­vaccination screening:
1.3.1 Check Hepatitis B immunization status/
documentation and Anti­HBs titre of all patients
1.3.2 Provide Hepatitis B immunization to those
Thalassemia patients who are non­immune for
Hepatitis B, i.e., those with anti­HBs
< 10 mIU/mL.
1.3.3 Re­immunization is not needed if there is a
documentation of a completed vaccination series
and anti­HBs levels ≥ 10 mIU/mL 1 to 2 months
post­vaccination.
1.4 Administration of the vaccine:
1.4.1 Give three doses of Hepatitis B vaccine with the
second and third doses at 1 and 6 months intervals,
as recommended by the manufacturer (as per
package insert). Administer 1.0 ml intramuscularly
(IM) into the deltoid muscle. Do not administer in
the gluteal region
35
 1.5 Post­vaccination Serological Testing (to ensure adequate
seroconversion and protection):
1.5.1 Check the level of anti­HBs one to two months
after completing the series . This is expected to be
≥ 10 mIU/mL.
1.6 Revaccination
1.6.1 If anti­HBs (HBsAb) levels are <10 mIU/mL 1 to 2
months post­vaccination (3 dose series), a full
second series of 3 doses should be given.
1.6.2 One to two months after completing the second
series, anti­HBs titre is expected to be ≥ 10
mIU/mL
1.6.3 If anti­HBs­titer remains <10mIU/ml after two
series, then he/she is considered a non­responder
and should be counselled accordingly. All such
patients should receive HBsAg testing.
1.6.4 HBsAg­negative patient who fails to seroconvert
should receive HBIG ( Hepatitis B Immunoglobulin)
if exposed to HBsAg positive blood products or
body fluid.

Hepatitis A vaccination
1. Consists of 2 doses given 6 months apart.
2. Children above one year should be given 720 Elisa units per
dose : 2 doses 6 months apart.
36
 3. Adults should be given 1440 Elisa units per dose : 2 doses 6
months apart.

Transition from Pediatric Care and Management of Adults

1.1 Transfer from pediatric to adult care must be planned and
discussed in advance for each individual and carried out
smoothly.

Prevention and management of Cardiac Complications

1.1 A cardiologist should be identified to collaborate.
1.2 Patients should have yearly cardiological assessment starting
from age 10. More frequent assessments may be required in
patients with heart disease.
1.3 Myocardial iron should be monitored by cardiac MRI T2* from
age 8­10 years.
1.4 Cardiac T2* should be maintained >20 milliseconds by
appropriate adjustment to chelation therapy.

Prevention and management of Endocrine Complications

1.1 A endocrinologist should be identified to collaborate.
1.2 Children should be monitored regularly and systematically for
growth and development, from diagnosis up until the time when
they have achieved full sexual maturity and final adult height.
1.3 Deviations from expected pattern should be investigated and
managed promptly.
37
 1.4 Children who are found to be growth hormone deficient
should receive replacement therapy.
1.5 Patients from age 10 should be checked annually for
biochemical evidence of glucose intolerance, and from age 12
for hypothyroidism and hypoparathyroidism, and deficiencies
treated appropriately.

Prevention and management of Liver Complications

1.1 Liver function tests should be monitored regularly.
1.2 Liver iron levels should be maintained within safe limits to
avoid progressive hepatic damage.
1.3 Adjustments to chelation or other treatment should be made
if liver dysfunction is associated with therapy.
1.4 Vaccination against hepatitis B infection should be standard
practice.
1.5 Chronic Hepatitis C virus infection should be mananged with
antiviral therapy aimed at sustained viral clearance.

Prevention and management of Bone Complications

1.1 Transfusion therapy should be initiated in time to prevent
irreversible deformities associated with bone marrow
expansion.
1.2 Bone changes related to desferrioxamine toxicity should be
suspected and investigated in children with bone/joint pain or
short stature.
38
 1.3 All patients should be encouraged to exercise, maintain a diet
rich in calcium and vitamin D.
1.4 Diagnosis of hypogonadism and other endocrinopathies
should be prompt, and adequate hormone replacement
therapy given.
1.5 Patients should be monitored regularly by bone densitometry
for osteopenia/osteoporosis, starting from adolescence.

Counselling
1.1 Patient/Family should be counselled on various aspects of the
disease including: Diagnosis, Management, and need for
regular follow­up.
1.2 Inheritance of disease, Extended Screening, Reproductive options
and Bone Marrow Transplantation should also be discussed.

Thalassemia minor / carrier

Clinical picture
1.1 Asymptomatic
1.2 Hb level normal or may have mild anemia (9­11 g/dL)
1.3 Hb levels may reduce under stress such as puberty, pregnancy
and infection.
1.4 Rarely have associated iron deficiency (unless significant loss
of blood; for example secondary to menorrhagia)
39
Lab Investigation
1.1 CBC & peripheral blood smear exam.
1.1.1 Low MCV and MCH
1.1.2 RBC counts higher for given Hb
1.2 Hemoglobin Analysis (HPLC method)
1.2.1 Raised HbA2 (>3.5%) in Beta­Thalassemia Carriers
1.3 Serum iron and Serum Ferritin
1.3.1 No Iron deficiency

Objectives of diagnosing carriers

1.1 Thalassemia carrier should be counseled on the importance
of testing their future partner for Thalassemia carrier state and
on the risk, if the partner is also a Thalassemia or other
hemoglobinopathy carrier.
1.2 If both couple are Thalassemia carriers:
1.2.1 With the help of appropriately experienced
professionals, inform them at the earliest
opportunity, the risk of having a child with
thalassemia disease and on available reproductive
options that include Prenatal Diagnosis and Pre­
Implantation Genetic Diagnosis. All such
counseling should be followed with an opportunity
for full discussion.

40
COVID­19 and Thalassemia Patients
• Patients with Thalassemia who are transfused and/or
splenectomised are considered to be in high risk group.
• They should be given appropriate information about the
disease, risk factors, sanitation and hygiene measures to
prevent exposure to COVID­19.
• They should be provided with appropriate personal protective
equipment (PPE ), such as masks. gloves and hand sanitizers.
• Health institutions should take measures to ensure safe access
to transfusion and other health care needs.
• Norms of social distancing should be observed in the wards.
• Despite lockdown ,transfusion dependent patients should
receive regular transfusions as per their requirements.
• Appointments should be appropriately scheduled to avoid
crowding and enable social distancing.
• Patients attending A&E should be fast­tracked. The Emergency
doctor should liaise with the treating doctor regarding further
management.
• Splenectomised patients should seek urgent medical advise in
case of fever. In these patients, antibiotics should be started
without waiting for lab investigations results. Investigations
should be done for both bacterial and viral causes.

41
 General Timetable for Clinical and Laboratory Evaluation
Category Measurement Check after this number As Initially Comments
Measurement of months clinically
Check after this 1 3 6 12 24 indicated

HPLC Haemoglobin fraction X

Baseline information DNA mapping (alpha and beta) X
Red blood cell phenotype (at baseline) X
Volume of packed red blood cells transfused X X
Blood Transfusion
Coombs (direct) X
Height X
Growth and Sitting height X
Development in Weight X
children Growth velocity X
Tanner Stage ( in children above the age of 10) X
Height X
Body measurements in
Weight X

42
CBC, reticulocytes X
Hematology
Coombs (direct)
Ferritin X
If there is evidence of hepatitis,
Liver iron X X histology is necessary.
Iron and toxicity Audiology evaluation X X
Vision screen X X
Ophthalmology evaluation X
Iron, TIBC X
Transferrin saturation X
AST, ALT X
Bilirubin (total) X
Bilirubin (direct) X
Hepatitis A serology X
Liver function and Hepatitis B serology X
disease
When hepatitis is active, do this
test annually. With undiagnosed
Hepatitis B PCR X X hepatitis, this may be monitored.
Hepatitis C serology X
 Evaluation of positive serology or
Hepatitis C PCR X undiagnosed hepatitis.
Have this before a liver biopsy.
p y
Patients with active hepatitis
Liver function and PT, PTT X X should have the test annually.
disease Albumin x
Liver MRI X
Ultrasound X
Fibroscan if available X X
Liver biopsy X
Chemistry panel X
Periodic Urinalysis X
Dental X
T3, free T4, TSH x delete Start at 5 years.
PTH X Start at 5 years.
Calcium, ionized calcium x Start at 5 years.
Fasting glucose X Start at 5 years.
Perform at 10, 12, 14, and 16
years

43
Glucose tolerance test / HBA1C x
fructosamine in diabetic patients x
IGF-1, IGF BP-3 X Perform at noted growth delay.
Endocrine Perform at noted delay in
puberty:11 years for girls and
LH-ICMA x X 12 years for boys
Perform at noted delay in
puberty:11 years for girls and
FSH x X 12 years for boys
Perform at noted delay in
puberty:11 years for girls and
Estradiol x X 12 years for boys
DEXA X
Osteoporosis Vitamin D level X
ECG X
ECG Holter
Stress test X
Echocardiography X X
Cardiology CMRI T2* X
Trust Guideline for Patients with an Absent or Dysfunctional Spleen

01/04/2020

01/04/2023

1267
5

44
5 01/04/2020

Contents Page number

1 Introduction 3

2 Vaccination Information Tables 4

3 Antibiotic Prophylaxis Information 6

4 Special patient groups/populations 7

Clinical audit standards 8

Summary of development and consultation process 8

Distribution list 8

References 8

45
 1. INTRODUCTION

DEFINITIONS
This guideline applies to patients who have recently undergone a
splenectomy or who have recently been diagnosed with a
dysfunctional spleen.
Splenectomy:
Elective, e.g., for haematological disease or splenic abscess, cysts,
mass and neoplasm.
Emergency, e.g., for traumatic injury to spleen or intra operative
splenic injury
Dysfunctional Spleen: This includes conditions such as homozygous
sickle cell disease and coeliac syndrome that may lead to splenic
dysfunction

RISKS OF ASPLENIA OR DYSFUNCTIONAL SPLEEN:

Overwhelming infection is a major risk in patients with an absent
or dysfunctional spleen and although uncommon, is associated with
a high mortality. These infections are often due to encapsulated
bacteria such as Streptococcus pneumoniae, Haemophilus influenzae
type b and Neisseria meningitidis and more than half of those infected
die. Other serious infections include malaria, babesiosis (caused by
tick bite) and Capnocytophagia canimorsus (caused by dog bites) and
secondary infections following influenza. For these reasons, it is
imperative that all patients with an absent or dysfunctional spleen
46
areappropriately immunised and receive appropriate antibiotic
prophylaxis.

CHECKLIST

Appropriate vaccinations given

Appropriate antibiotic prophylaxis prescribed
Patient information leaflet and Splenectomy card given
(Available from pharmacy. It is the responsibility of the team
looking after the patient to ensure this happens).

http://www.christie.nhs.uk/media/245400/SplenectomyCard.pdf

Advise patients that they may wish to invest in an alert

bracelet or pendant

EDL informs GP that a splenectomy has been performed.

2. VACCINATION INFORMATION

Elective Splenectomy
Ideally start immunisation course at least TWO (ideally four to six)
weeks prior to surgery.
47
Emergency Splenectomy
Ideally start immunisation course at least TWO weeks post surgery.
Given the changing pattern of routine vaccination, patients of
different ages may have different “routine” vaccination histories. It is
therefore absolutely essential to assess vaccination requirements
against an individual’s vaccination history.

C
D
C
D

C
D
C
D

48
 %%'

C
D
C
D
C
D
C

C
D
C
D
C

49
 3. ANTIBIOTIC PROPHYLAXIS
All patients should be offered lifelong antibiotic prophylaxis. The
increased risk of infection in patients with hyposplenism is life long,
but is highest early after splenectomy, the biggest risk being from
pneumococcal infection.
Patients deemed to be at highest risk
• Aged <16 years or >50 years old
• Inadequate serological response to pneumococcal vaccination
• A history of previous invasive pneumococcal disease
• Splenectomy for underlying haematological malignancy,
particularly those who have received splenic irradiation or who
have ongoing GvHD are also at continuing high risk.
• Patients with active ongoing graft­versus­host disease

50
 6

Standby courses of Antibiotics

Patients may develop infection despite vaccination and
antimicrobial prophylaxis; these patients require treatment with
broad spectrum antibiotics as soon as possible. All patients should
keep a supply of antibiotics at home, changing from prophylactic to
therapeutic doses if they develop a febrile illness. This is particularly
important for those who do not, or will not take prophylactic
antibiotics or due to compliance problems. This should be discussed
on an individual basis with the patient. If the patient requires a
standby course of antibiotics, we recommend Amoxicillin 500mg tds
or Clarithromycin 500mg bd (if penicillin allergy). Patients should be
advised of the importance of seeking medical attention as soon as
possible if they develop any signs of infection e.g. sore throat, fever,
malaise, severe headache and flu­like symptoms.

51
 4. SPECIAL PATIENT GROUPS/SITUATIONS

Chemotherapy and Radiotherapy (or other immunosuppres­

sive treatment)
• Ideally, vaccinations should be given at least TWO weeks
(ideally 4­6 weeks) before initiation of treatment such as
chemotherapy or radiotherapy. Where it is not possible to
vaccinate beforehand, splenectomy, chemotherapy or
radiotherapy should never be delayed.
• If it is not practicable to vaccinate TWO weeks before the
initiation of chemotherapy and/or radiotherapy, immunisation
can be delayed until at least THREE months after completion
of therapy in order to maximise the response to the vaccine,
whilst ensuring adequate antibiotic cover is prescribed in the
interim.
• Individuals with immunosuppression should be vaccinated in
accordance with the standard schedule but it should be borne
in mind that these individuals may not make a full antibody
response.

Pregnancy/Breast­feeding
• All of the vaccines may be given during pregnancy and breast­
feeding when protection is required without delay.

52
Travel
• Patients should be educated as to the potential risks of
overseas travel, particularly with regards malaria and unusual
infections, for example those resulting from animal bites and
tick bites.

Animal Bites
• Human, dog or other bites may be fatal if untreated due to
infection with Capnocytophagia canimorsus and other virulent
organisms. All animal bites need to be treated quickly with
antibiotics.

Tick bites
• Babesiosis is a rare tick borne infection that can cause
moderate to severe disease, including haemolytic anaemias.
Therefore it is essential to take precautions against being
bitten in endemic areas.

Clinical audit standards

All patients undergoing either elective or emergency splenectomy
should be managed according to the Trust Guideline.
All patients should be given written information and carry an ‘I have
no functioning spleen’ card to alert healthcare professionals to the
risk of overwhelming infection.
This guideline will be updated in accordance with changes in the
53
recommendations made in “Immunisation Against Infectious Disease
– The Green Book”.
Summary of development and consultation process undertaken
before registration and dissemination process
The authors listed above on behalf of the Antimicrobial
Subcommittee, which has agreed the final content, drafted the
guideline. During its development it was circulated for comment to
Haematology, Oncology, Surgical and Paediatrics Directorates.
Comments received from these listed parties have been addressed
and incorporated into this guideline. This guideline has been extended
to include neonates, as well as paediatrics and adults.

Distribution List
The Guidelines Assessment Panel has ratified this guideline. The
Guideline has been distributed to all clinical directors and a copy is
available on the Trust Intranet.

References
Department of Health – Immunisation against Infectious Disease
2013 – “The Green Book”
– updated version available online:
https://www.gov.uk/government/uploads/system/uploads/attach
ment_data/file/309218/Green_Book_Chapter_7_v1_3.pdf

54
 Chelator Toxicity Monitoring

Deferoxamine Deferasirox Deferiprone

Complete blood count (CBC); Weekly
absolute neutrophil count
(ANC)
Liver function tests (LFTS) Every 3 to 4 weeks Every 3 months
Creatinine Every 3 months Every 3 to 4 weeks Every 3 months
Urine microalbumin/ Every 3 months Every 3 to 4 weeks
Creatinine/ACR

55
Urine glucose Every 3 to 4 weeks
Zinc, copper, calcium and Annually Annually Annually
magnesium
Electrolytes Every 3 to 4 weeks
Eye exam Annually Annually Annually
Audiogram Annually Annually Annually
Sitting height Biannually Biannually Biannually
Height/weight Every 3 to 4 weeks Every 3 to 4 weeks Every 3 to 4 weeks
Clinical symptoms (nausea, Every 3 to 4 weeks Every 3 to 4 weeks Every 3 to 4 weeks
diarrhea, color-vision change)
Notes:

56
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