thalassemia
TRANSCRIPT
THALASSEMIA
WORLD THALASSEMIA DAY-MAY 8
Dr. VENKATESH
OBJECTIVES
To know :
• Basic features of thalassemia syndromes
• Transfusion protocols in thalassemia
• Chelation therapy in thalassemia
• Supportive care in thalassemic patients
• Follow-up guidelines
• Hemtopoitic Stem cell transplantation
• Future aspects.
DEFINITION
Thalassemia is a group of inherited disorders of hemoglobin synthesis characterized by a reduced or absent one or more of the globin chains of adult hemoglobin.
They characterised by varying degrees of ineffective hematopoiesis and increased hemolysis
ICD classification: D-56
HEMOGLOBIN A
Fetal Hemoglobin (2 alpha, 2 gamma)
Hemoglobin A2 (2 alpha, 2 delta)
Small amounts in body
α
αβ
β
Copyright ©1997 BMJ Publishing Group Ltd.
NORMAL HUMAN HAEMOGLOBINS
Haemoglobin Structural formula
Adult Hb-A 2 2 97%
Hb-A2 2 2 1.5-3.2%
Fetal Hb-F 2 2 0.5-1%
Embryonic Hb-Gower 1 2 2
Hb-Gower 2 2 2
Hb-Portland 2 2
GENETIC TYPES OF THALASSEMIA :
There are two basic groups of thalassemia.
Alpha ( )Thalassemia
In alpha-thalassemia, the alpha genes are deleted;
loss of one gene (α-/α) or both genes (α-/α-) from each
chromosome 16 may occur, in association with the
production of some or no alpha globin chains
Beta ( )Thalassemia
In beta-thalassemia defective production usually
results from disabling point mutations causing no (β0) or
reduced (β-) beta chain production.
CHROMOSOMES
Thalassemia is inherited as an autosmal recessive
disease.
EPIDEMIOLOGY
Recent data indicate that about 7% of the world
population is carrier of hemoglobin disorder.
About 100,000 children are born every year world
over with the homozygous state for thalassemia.
There are around 65,000 - 67,000 thalassemia
patients in our country.
In India prevalence of this gene varies, 1-17 %
(3.3%).
Common in certain Communities like sindhis,
punjabis, khatris, khukrajas, bhanushalies, baniyas,
lohanas, kuchies, mahars, kolies, agries, goudas,
lingayats .
ALPHA THALASSEMIA
Alpha Thalassemia: deficient/absent alpha subunits
Excess beta subunits
Excess gamma subunits newborns
Tetramers formed:
Hemoglobin H adults
Hemoglobin Bart’s newborns
types:
Silent Carrier
Trait (Minor)
Hemoglobin H Disease
Hydrops fetalis(Hb Bart’s)
GENETIC BASIS OF ALPHA THALASSEMIA
Encoding genes on chromosome 16 (short arm)
Each cell has 4 copies of the alpha globin gene
Each gene responsible for ¼ production of alpha globin
4 possible mutation states:
Loss of ONE gene silent carrier
Loss of TWO genes thalassemia minor (trait)
Loss of THREE genes Hemoglobin H Accumulation of beta chains
Association of beta chains in groups of 4 Hemoglobin H
Loss of FOUR genes Hemoglobin Barts NO alpha chains produced ∴ only gamma chains present
Association of 4 gamma chains Hemoglobin Barts
CLASSIFICATION & TERMINOLOGY
ALPHA THALASSEMIA
• Normal /
• Silent carrier - /
• Minor -/-
--/
• Hb H disease --/-
• Barts hydrops fetalis --/--
CLINICAL OUTCOMES OF ALPHA THALASSEMIA
Silent carriers
• asymptomatic
• “normal”
Alpha Thalassemia trait
• no anemia /mild anemia
• microcytosis
-unusually small red blood cells due to fewer Hb in RBC
Hb H disease
• microcytosis & hemolysis (breakdown of RBC)
- results in severe anemia
• bone deformities
• splenomegaly (enlargement of spleen)
• “severe and life threatening”
• Golf ball inclusions on micrscopy
CLINICAL OUTCOMES OF ALPHA THALASSEMIA
Bart’s Hydrops fetalis
• Hb Bart’s
• fatal hydrops fetalis
- fluid build-up in fetal compartments, leads to
death occurs in utero
BETA THALASSEMIA
Beta Thalassemia: deficient/absent beta subunits
Commonly found in Mediterranean, Middle East, Asia,
and Africa
Three types:
Minor
Intermedia
Major (Cooley anemia)
asymptomatic at birth as HbF functions
GENETIC BASIS OF BETA THALASSEMIA
Encoding genes on chromosome 11 (short arm)
Each cell contains 2 copies of beta globin gene
beta globin protein level = alpha globin protein level
Suppression of gene more likely than deletion
2 mutations: beta-+-thal / beta-0-thal
“Loss” of ONE gene thalassemia minor (trait)
“Loss” of BOTH gene complex picture
2 beta-+-thal thalassemia intermedia / thalassemia
major
2 beta-0-thal thalassemia major
Excess of alpha globin chains
CLASSIFICATION & TERMINOLOGY
BETA THALASSEMIA
• Normal /
• Minor /0
/+
• Intermedia 0/+
+/+
• Major 0/0
+/
CLINICAL OUTCOMES OF BETA THALASSEMIA
Beta Thalassemia minor (trait)
• asymptomatic
• microcytosis
• minor anemia
• Elevated HbA2 >3.4%
Beta Thalassemia intermedia .
• symptoms similar to Cooley Anemia but less severe
Beta Thalassemia major (Cooley Anemia)
• most severe form
• moderate to severe anemia
• intramedullary hemolysis (RBC die before full development)
• peripheral hemolysis & splenomegaly
• skeletal abnormalities (overcompensation by bone marrow)
• congestive heart failure,pulmonary hypertension
PATHOPHYSIOLOGY
Disturbance of ratio between Alpha & non
alpha globin chain synthesis then absent or
decrease production of one or more globin
chains
Formation of abnormal Hb structures
Ineffective erythropoiesis
Excessive RBCs Destruction
Iron Overload
Extra-medullary hematopoiesis
PATHOPHYSIOLOGY..CONT..
SIGNS & SYMPTOMS
Beta Thalassaemia Minor :Usually no signs or symptoms except for a mild persistent anemia not responding to hematinics.
BetaThalassaemia Major : manifests after 6 months1. Pallor- fatigue, irritability2. Growth retardation.3. Recurrent infections4. Bony abnormalities specially of the facial
bones,hemolytic facies, caput quadtratum5. Enlarged spleen and liver.6. Delayed sexual development7. Features of complications .
THALASSEMIA COMPLICATIONS
Complications can be grouped as
(1) transfusion-transmitted infections,
(2) transfusional iron overload,
(3) toxicities of iron chelation therapy, and
(4) bacterial infections
COMPLICTIONS ..CONT..
Cardiac complications
Liver complications
Endocrine complications
Bone complications
Other complications
Infections: yersinia,parvovirus B19
Dental Complications
Growth retardation
Leg ulcers
CARDIAC COMPLICATIONS
Cardiac dysfunction(both systolic and diastolic dysfuction)
Arrhythmias
Ferritin greater than 2500 mg/L or a liver iron concentration > 15 mg Fe/g dry weightis associated with high risk of cardiac death in thalassemia
ferritin and liver iron may not correlate with cardiac iron load, cardiac iron can be specifically and reproducibly measured using cardiac MRI T2*. Cardiac MRI T2* less than 20 ms correlates with a progressive and significant decline in LVEF
CARDIAC COMPLICATIONS CONT..
Monitoring: 6 monthly cardiac physical examination,
cardiac function yearly starting at age of 10 years, if
history suggestive of arrhythmias ECG, 24-hour
Holter monitoring should be done.
Chelation therapy to reduce high iron load lowers
the likelihood of developing cardiac dysfunction
CARDIAC COMPLICATIONS..CONT
Cardiac MRI T2 Cardiac iron load Cardiac function intervention
values greater
than 20 ms
not usually
associated with
significant iron load
not usually
associated with
cardiac dysfunction
compliance and
importance of
chelation stressed
values between 10
and 20 ms
significant cardiac
iron deposition
a risk of eventual
cardiac
decompensation
more aggressive
chelation program
should be
implemented
values < 10 ms Very high cardiac
iron load
significant risk of
more immediate
cardiac
decompensation
without aggressive
intervention
Aggressive
chelation therapy
should be started
immediately and
cardiac function
monitored
CARDIAC COMPLICATIONS..CONT
Where cardiac MRI T2* is not available, • chelationdecisions should be based on ferritin, LIC and cardiac function assessment
Patients with ferritin > 2500 mg/ml and LIC >15g Fe/g dry weight should be chelated more aggressively.
those with ferritin < 2500 mg/ml and LIC 7 – 15 g Fe/g dry weight should have chelation adjusted accordingly and compliance encouraged.
Cardiologic intervention and management for heart failure and arrhythmia should follow cardiology standards apart from aggressive chelation
LIVER COMPLICATIONS
includes- transfusion-related viral hepatitis
(Hepatitis B, C), iron overload, drug toxicity, and
biliary disease due to gallstones.
Liver enzymes should be monitored routinely.
Liver iron concentration should be monitored
routinely and chelation therapy initiated and
adjusted to reduce complications of iron overload.
In the presence of elevated liver iron, liver fibrosis,
and cirrhosis may be accelerated by alcohol, liver-
toxic drugs, and untreated viral hepatitis, Limit such
exposure.
ENDOCRINE COMPLICATIONS
Iron overload is responsible for dysfunction of many
of endocrine glands like thyroid, parathyroid
pituitary gland, gonads and pancreas.
These include-
short stature (34%),
delayed puberty, hypogonadotropic hypogonadism (35
– 55%),
hypothyroidism (10%),
hypoparathyroidism (4%), and
diabetes mellitus (5.6 – 20%)
ENDOCRINE COMPLICATIONS -
INTERVENTIONS
Short stature-
The diagnosis of growth hormone deficiency, other
hormonal or nutritional deficiencies or deferoxamine
toxicity should be considered
Growth hormone stimulation testing should be done
and, if indicated, growth hormone therapy started
Hypothyroidism
TSH levels should be measured annually beginning at
12 years of age since hypothyroidism often develops
after adolescence.
Hypothyroidism should be treated with thyroid hormone
replacement.
ENDOCRINE COMPLICATIONS -
INTERVENTIONS
Impaired Glucose Tolerance and Diabetes
Improvement of iron load with adequate combination
chelation therapy may decrease insulin resistance and
decrease glucose intolerance
Impaired glucose tolerance and diabetes should be
managed as per diabetes protocols with emphasis on
glycemic control, diet, exercise, and management of
complications.
ENDOCRINE COMPLICATIONS -
INTERVENTIONS
Delayed Puberty and Hypogonadism
most common endocrine complication
all children should be assessed yearly from the age of 10
years
All patients with delayed puberty or hypogonadism should
receive appropriate investigations including bone age and
hormonal assessments, hormonal replacement therapy, and
subsequent follow-up by an endocrinologist
Hypoparathyroidism
All patients over the age of 12 years should have calcium and
phosphate levels checked at least every 6 months.
If these are abnormal, parathyroid hormone level should be
measured. Hypoparathyroidism should be managed as per
endocrine standards
BONE COMPLICATIONS
Bone disorders are common and multifactorial in patients with thalassemia .
Related to inadequate transfusion, iron-overload, over-chelation, and other endocrine factors contribute to the development of osteopenia and osteoporosis
Interventions:
Adequate blood transfusions
Adequate chelation therapy should be maintained
No Over-chelation
Hormone replacement therapy
Calcitonin,bisphosphonates
Diet rich in calcium and vitamin D
HYPERSPLENISM- SPLENECTOMY
Indictions of splenectomy
An increase in the yearly requirement of packed cells
more than 1.5 times the basal requirement, i.e. packed
cell 200 to 220 cc per kg/ year.
Massive splenic enlargement posing risk of splenic
rupture, or when it is associated with left upper
quadrant pain or erly satiety
Presence of leukopenia or thrombocytopenia due to
hyperspleenism
Splenectomy should be delayed till the patientis 5
years of age as there is risk of overwhleming sepsis
below this age
Risk of post-splenectomy serious infections can be
reduced by:
Immunization against pneumococcal, meningococcal,
and Hib and salmonella typhi infection atleast 3 weeks
before splenectomy
Chemoprophylaxis with oral penicillin,
125 mg twice daily for children upto 2 years
250 mg twice daily for children 2 years and above
Post splenectomy there may be transient or
persistent thrombocytosis. Aspirin 50-100 mg/day
for patients if platelet count >8,00,000/mm3
IMMUNIZATION PRIOR TO SPLENECTOMY
Pneumcoccal vaccine. 0.5 ml SC
If child has received a complete primary course PLUS
a single booster dose
Age<2 years: ( give one dose PCV13 Prevenar13 )
Age > 2years: ( give one dose PPV 23 Pneumovax 23
revaccinate after 3 years )
If child has not recieved primary course
Age 16 months – 5years : give two doses PCV13 Prevenar13
8 weeks apart
If aged 5-18 years - one dose
give one dose PPV 23 Pneumovax 23 at least 8 weeks after
the last PCV13 dose , revaccinate after 3 years.
Meningococcal vaccine:
Quadravalent meningococcal (Menactra) 0.5
mL IM upper deltoid.
o Children aged 2 through 6 years :Two doses of
Menactra® at least 8 weeks apart, followed by a single
booster dose 3 years later and then a single booster
dose every 5 years
Children aged 7 years and over and adults through
55 years :Two doses of Menactra® at least 8 weeks
apart, followed by a single booster dose every 5 years
Haemophilus b conjugate : One dose
regardless of previous vaccination history
RECOMMENDED MONITORING FOR COMPLICATIONS
OF B-THALASSEMIA
RECOMMENDED MONITORING FOR
COMPLICATIONS OF B-THALASSEMIA
CAUSES OF DEATH
Congestive heart failure
Arrhythmia
Sepsis secondary to increased susceptability to
infection post spleenectomy
Multiorgan failure due to hemochromatosis
LABORATORY
DIAGNOSIS OF
THALASSEMIA44
Complete Blood Count (CBC) with red cell indices and Peripheral Blood Film (PBF) Examination and reticulocyte count.
Hb low, total RBC count and Hct decreased
Thalassemics have uniform microcytosis with out increase in RDW
PS of Thalassemia Child
Characteristic bizarre picture of red cells, which are microcytic, hypochromic, with poikilocytosis, polychromasia, moderate basophilic stippling, and fragmented erythrocytes, target cells, and large number of normoblasts
Thalassemia trait Iron deficiency
anemia
RDW Normal(11.5-14.5) high
RBC count High relative to
hematocrit,Hb
levels
low
Thalassemia major Iron deficiency
anemia
serum Iron
levels
Serum iron high
Sr.ferritin high
TIBC decreased
Transferrin
saturation:
increased
Low
Low
Increased
decreased
The baseline serum ferritin and liver enzymes
including ALT, AST, bilirubin, lactate dehydrogenase
(LDH) should be measured.
Full red cell phenoptype [C, c, D, E, e, K, k, Jka,
Jkb, Fya, Fyb, Kpa, Kpb, MNS, Lewis]
Serologic testing for hepatitis A, B, and C, and HIV
should be performed as baseline measures.
All first-degree family members should undergo
HLA-typing, if potential future allogeneic
hematopoietic stem cell transplant is considered an
option.
HB ELECTROPHORESIS
LAB DIAGNOSIS ..CONT. Osmotic fragility test : decreased
Urinary urobilinogen: increased (Ehrlich test)
Stool examination: dark stools, increased
stercobilinogen.
Radiological changes: seen after 1 year
X-ray of metacarpals,ribs, vertebra show thinning of cortex
X-ray of skull shows “hair on end appearance”
Generalised skeletal osteoporosis
MANAGEMENT OF THALASSEMIA MAJOR
Comprehensive management includes the following:
• Confirmation of the diagnosis
• Correction of anemia– Packed red cell transfusions
• Removal of excess iron– Chelation Therapy
• Management of complications – Endocrine and
Cardiac complications
• Pharmacological methods to increase gamma chain synthesis
• Supportive care
• Curative Treatment– Stem Cell Transplantation
• Future treatment– Gene replacement therapy.
A team approach includes:
• Pediatric hematologist,
• Pediatrician,
• Blood transfusion specialist
• Endocrinologist,
• Psychologist and
• Social worker, etc
TRANSFUSION THERAPY IN
THALASSEMIA
Transfusion therapy in thalassemia has
two goals:
• To prevent anemia
• To suppress endogenous erythropoiesis
Regular Blood Transfusions are Presently the
Mainstay of Treatment of Thalassemia Major.
Concept of Neocyte transfusion
TRANSFUSION PROTOCOLS
Palliative– Pretransfusion - Hb level is around < 7 gm% and mean Hb maintained is < 8.5 gm/dl.
Hyper Transfusion– Pretransfusion Hb level is
around > 10gm% and mean Hb. Maintained is
> 12 gm%.
Super Transfusion– Pretransfusion Hb level is
around > 12gm% and mean Hb. Maintained is
>14gm%.
Moderate– Transfusion- Pretransfusion- Hb level is around 9-10.5 gm% and mean Hb. Maintained is >12gm %.
Current recommendation?
TYPE OF TRANSFUSION
Leukoreduced packed red cell transfusion is
desired type of blood for thalassemic children
Reduction of leukocytes to 5000000 is considered
adequate.(reduced by 70%)
It helps in prevention of transfusion reactions and is
achieved by centrifugation;/saline washing/filtration.
METHODS FOR LEUKODEPLETION
Centrifugation– Packed red cell transfusions
Saline-cell washing (Triple Saline Washed)
Deglycerolized–red cells.
Third generation leucocyte filters
Irradiated blood cells
BENEFITS OF BLOOD TRANFUSION-
THALASSEMIA
Improves tissue oxygenation, and prevents chronic
hypoxia
Improves normal growth and development
Prevents erythropoiesis thus avoiding expansion of
the bone marrow and extra medullary
erythropoiesis
Reduces hemolytic facies
Reduces hepatosplenomegaly and cardiomyopathy
Reduces gastro-intestinal absorption of iron.
WHEN TO START THE TRANSFUSION
Blood transfusion is started as soon as diagnosis
firmly established (Except in children > 18 months of
age).
If age is > 18 months, these children are observed to r/o
Thalassemia Intermedia and if Hb drops < 7 gms%,
regular transfusion started.
The most ideal way to transfuse thalassemics is using
group and type specific saline washed packed red
cells (HCT - 65 to 75%) that are compatible by direct
antiglobulin test (Coomb’s crossmatched)
RATE AND FREQUENCY OF
TRANSFUSIONS
10-15 ml/kg of saline washed packed red cells every 3 to 4 weeks.
Rate not more than 5 ml/kg/hr, however, in patients with cardiac dysfunction not more than 2-3 ml/kg/hr should be given.
Shorter intervals of 2 to 3 weeks are more physiological.
Average time taken is 3-4 hours
Approximately 180 ml/kg of red cells are required to be transfused per year in non-splenectomized, nonsensitized patients to maintain the hemoglobinabove 10 gms%, whereas splenectomized patients require 133 ml/kg per year.
Even without hypersplenism, the requirement is 30%
higher in non-splenectomized patients
COMPLICATIONS OF TRANSFUSION
NHFTR (Non hemolytic febrile transfusion reaction)
Allergic reactions
Acute hemolytic reactions
Delayed hemolytic reactions
TRALI-transfusion related acute lung injury
TACO- transfusion associated circulatory overload
Alloimmunizaton.
Transfusion transmitted infections
Iron overload
Steps to Prevent These Infections Include
Screening of blood products.
All thalassemic children should recieve hepatitis vaccination if not previously immunised
Leukodepletion can minimize CMV infection
IRON OVERLOAD AND CHELATION THERAPY
Iron Overload Occurs in Thalassemic Patients
due to
Treatment with multiple transfusions
Ineffective erythropoiesis
Excessive dietary absorption of iron from gut, to
compensate the large turnover of red cell mass
Lack of physiologic excretory mechanism for the
excess iron
The goal of iron chelation is to reduce the iron
store and subsequently maintain at low level
(sr.ferritin less than 1000ng/ml).
INITIATION OF CHELATION THERAPY
Serum ferritin >1000ng/dl
Patient has received 15-20 transfusions
Hepatic iron concentration exceeds 3.2mg/ g dry
weight
CHELATING AGENTS
Deferoxamine(DFO)
Route:SC/IV
Dose: 25-50 mg/kg/day
Schedule: over 8 to 10 hrs for 5-6 nights a week with the
help of subcutaneous desferal infusion pump
MOA:chelates loosely bound iron, iron from
ferritin,hemosiderin ,not from transferrin
Excretion :Urine(80%,urine red)/Feces
Plasma clearance t1/2: 20 minutes
Adverse effects Local skin reaction, ototoxicity, infections
,ophthalmic toxicity, skeletal impairment
Monitoring Long bone films in growing children, annual
eye and ear check-up
CONSIDERATION OF AGGRESSIVE CHELATION
THERAPY
Severe iron over load
Persistently very high ferritin value
Liver iron >15mg/ g dry weight
Significant cardiac disease
Cardiac arrhythmias
Evidence of falling left ventricular function
Evidence of very severe heart iron loading(MRI T2* <6
ms)
Prior to bone marrow transplantation when rapid
reversal of iron loading may be desirable
tab Vitamin C 1hr prior to infusion .
Deferipone(Kelfer)
It mobilizes iron from transferrin, ferritin, and
hemosiderin.
Dose: 75 to 100 mg/kg body weight/day in
three to four divided doses
Excretion:Urine
Plasma clearance t1/2:53-166 minutes
Adverse effects: Agranulocytosis, GIT
disturbances,transaminase elevation,
arthralgias
Monitoring:Weekly CBC
DEFERIPONE ..CONT
Drug should be discontinued whenever
Total count drops to < 3000/mm 3
Absolute neutophil count drops to < 1000/mm 3
Zinc deficiency may develop, zinc supplementation
may be necessary
It should be first line drug for patients not receiving
DFO because of high cost, toxicity or poor
compliance of the later.
Deferasirox (exjade)
A novel chelating agent belongs to tridentate tiazole,with
high affinity to iron as Fe+++ and chelates at a ratio of
2:1 (Deferasirox: Iron).
Dose :20-30 mg/kg/day
Schedule: daily ,OD
Excretion:Feces
Plasma clearance t1/2:1-16 hours
It should be given approximately same time each day on
an empty stomach 30 minutes prior to food. Tablet
should be dispersed in water/orange /apple juice.
It is available as 250/500 mg tablet for oral suspension
dispersible tablets
Monitoring:Monthly RFT, LFT and urine analysis
Side effects: GI disturbances , rash, renal dysfunction
SHUTTLE HYPOTHESIS
Co-administration of ICL 670 (Deferasirox) with Inj
DFO has synergic effect and helps in reducing dose
of both the drugs thus improving the compliance
and cost of the treatment as is done with oral
chelation therapy with deriprone and inj. desferal.
Shuttle effect
also seen with this combination, as ICL 670-
Deferasirox acts as intracellular chelator and DFO as
extracellular.
MANIPULATION OF HBF SWITCHING
Hydroxyurea
Histone Deacetylase Inhibitors
Butyric Acid Analogs
5-azacytidine,( risk of cancer –not used now)
Erythropoietin has been tried to induce HbF
production with varying success
STEM CELL TRANSPLANTATION
This is only the curative therapy available today.
Sources of stem cells:Bone Marrow, Peripheral
Blood, Cord Blood,Fetal Liver.
Though expensive, it is cost effective as compared
to yearly cost of regular blood transfusion and
chelation therapy.
cost 8-10 lakhs.
Umblical cord stem cells have good results(lower
GVHD, longer engraftment)
GENE THERAPY
Lenti Viral vector derived from Human
Immunodeficiency Virus, where a large fragment of
human beta gene and its locus control region, have
been introduced, though experimental, more
effectiv therapies will become available near future
to cure the disease.
PREVENTION OF THALASSEMIA-CARRIER
SCREENING
Thalassemia minor or carrier state can be easily detected in a person by doing simple blood test HbA2 by hemoglobin electrophoresis or variant machine or column chromatography
Prevention includes population education, mass screening, genetic counseling and antenatal diagnosis and therapeutic abortion of affected pregnancy
Carrier detection:The only confirmatory test is HbA2 estimation.
To conduct an effective mass screening program, the targeted population should belong to the premarital and newly married groups, i.e. before they have begun their families.
ANTENATAL DIAGNOSIS
When both partners, who are thalassemia minors, plan to have their baby, they are told to report to their hematologist as soon as possible after pregnancy is confirmed.
Chorionic villous sampling (CVS) done between 9th and 11th week of pregnancy.
amniocentesis or cordocentesis-16 to 18 weeks of pregnancy.
Test result:
‘Affected’ which means the fetus has thalassemia
major, or
‘Unaffected’ meaning that the fetus is either
thalassemia minor or normal.
Affected fetuses are advised to be terminated and
unaffected fetuses to be continued
REFERENCES
IAP TEXT BOOK OF PEDIATRICS 5th Ed
Advances in pediatrics pedicon 2012
IAP Pediatric Hematology
Nelson Text Book Pediatrics
Standards for the Clinical Care of Children and
Adults with Thalassaemia in the UK
Guidelines for the Clinical Care of Patients with
Thalassemia in Canada
Thank you