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THALASSEMIA


HEMATO-ONCOLOGY DIVISION
PEDIATRIC DEPARTEMENT
MEDICAL SCHOOL
UNIVERSITY OF NORTH SUMATERA


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HEMOGLOBINOPATHIES

CLASSIFIED INTO TWO MAJOR GROUPS

1. THALASSEMIAS
Quantitative deficiencies in the
production of globin chains

2. HEMOGLOBINS DISORDER
Structural abnormalities of globin chains

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CLASSIFICATION OF THE COMMON
THALASSEMIAS AND RELATED DISORDERS
-Thalassemia

+

o
- Thalassemia

i
+
Hb Lepore thalassemia
(

)
o

(
A
)
o

- Thalassemia
()
o
- Thalassemia
-or- Thalassemia associated with -chain variants
Hb S -Thalassemia
Hb E -Thalassemia
many others
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CLASSIFICATION OF THE COMMON
THALASSEMIAS AND RELATED DISORDERS

-Thalassemia

+
(deletion)

+
(non-deletion)

o
Hereditary persistence of HbF
Deletion
Non-deletion
A

+ G

+

Unlike to -globin gene cluster


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- THALASSEMIA

DIAGNOSE :
African, Mediteranian, Middle Eastern,
Chinese, or Southeast Asian ancestry

Microcytic, hypochromic anemia of
variable severity

Hemoglobin Barts detected by neonatal
screening
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PATOPHYSIOLOGY
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USUAL
GENOTYP
ES
-
GENE
NUMBE
R
CLINICAL
FEATURE
S
HEMOGLOBIN
ELECTROPHORESIS
BIRTH > 6 MO
/ 4 NORMAL NORMAL NORMAL
- / 3
SILENT
CARRIER
0 3% Hb Barts NORMAL
-- / or
- / -
2
- THAL
TRAIT
2 10% Hb Barts NORMAL
-- / - 1
Hb H
DISEASE
15 30% Hb
Barts
Hb H
PRESENT
-- / -- 0
FETAL
HYDROP
S
> 75% Hb Bart,s -
Table 1. The - thalassemias
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Thalassemia _alpha
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TREATMENT
-thalassemia trait require no treatment

Hb H disease should receive folic acid
avoid the same oxidant drugs
Transfusions may be required
Splenectomy
Genetic counseling and prenatal diagnosis

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-THALASSEMIA

Essentials of diagnosis & typical features

-thalassemia minor
- mild hypochromic microcytic anemia
Haemoglobi 90-110g/l
Mean cell volume 50-70 fl
mean corpuscular haemoglobin 20-22 pq
- no clinical features, patient asymptomatic
- often diagnosed on routine blood count
- raised Hb A
2
level
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-Thalassemia major :
severe anemia
Blood film
- pronounced variation in red cell size and shape
- pale (hypochromic) red cells
- target cells
- basophillic stippling
- nucleated red cells
- moderately raised reticulocyte count
infants are well at birth but develop anemia in first
few months of life when switch occurs from to
globin chains
progressive splenomegaly; iron loading; proneness to
infection
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SCREENING
Peripheral blood stain
Mean corpuscular volume (MCV) value
and MCH value
Mentzer index
RDW index
Hb-electroforese


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PRENATAL DIAGNOSIS
If mother suffered thalassemia
DNA analysis by CVS (chorion vilus
sampling) at 9-12
th
week of gestation
PCR rapid detection of mutation
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Thalassemia_beta
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Thalassemia minor
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Thalassemia major
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22
thalassemia
Hb elektroforese
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TREATMENT
red cell transfusion : PRC, neocyte
infective complication
- viral hepatitis
- Yersinia infection
splenectomy
chelation theraphy : desferrioxamine
if serum ferritin 1500 g or got
transfusion 10-20 x
Dose of desferrioxamine :20-40 mg/kgBW
for children
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INFECTIONS IN THALASSAEMIA MAJOR
The second commonest cause of death in thalassaemia major
The reasons for infection are :
Transmission by blood transfusion
Altered host immunity due to :
Hypersplenisme
Iron overload and chelation therapy
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HEPATITIS C VIRUS
RNA virus was first characterized in 1989
Antibodies after infection are strain specific
Preventive : careful selection of voluntary donors and
blood donor screening

The severity of hep.C greater because of:
Concomitant iron overload
Other concurrent viral infections ( HBV, HIV )

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COMPLICATIONS OF INFECTION
Acute infection
Chronic infection
Cirrhosis
End-stage liver disease
Hepatocellular carcinoma (HCC)
Non hepatic manifestations : arthritis, keratoconjunctivitis
sicca, lichen planus, glomerulonephritis, and vasculitis.
Essential mixed cryoglobulinemia (EMC)
Porphyria cutanea tarda

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DIAGNOSIS AND MONITORING
Antibody Testing
HCV RNA
Detected by PCR
Moct reliable indicator of viral activity
Precedes sALT elevation in acute or recurrent cases by
2-10 weeks
Anti HCV
Detected by RIBA
Liver biopsy
Determined of the extend of liver disease
Assesment liver tissue iron load
Monitoring progression and response to antiviral virus
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TREATMENT
Selection of patients for therapy
Confirmed presence of HCV-RNA
Moderate to high sALT level
Abnormal liver histology
Presence of persistent HCV RNA sufficient to consider
treatment
Response to treatment
Biochemical (sALT)
Virological (HCV-RNA)
The timing of the above response
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Treatment regiment : Interferone
Dose: 3 MU sc or IM , 3 times daily
Duration : 12 24 months
Side effect : flu like symptoms, insomnia, cognitive
and mood changes, neutropenia, thrombocytopenia,
hypothyroidism, heart failure
Monitoring side effect : thyroid function, blood
counts

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RE-TREATMENT
if non response, relaps, partial response, and
breakthrough patient

Re-treatment options :
Recombinant interferon with Ribavirin for 6 months
The same drug with longer periode (12-24 months),
or higher dose for 6-12 months
A different interferon
Side effect : haemolysis in thalassaemia patients

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Management of liver disease is important for :
Children
Cirrhosis
Immunosuppresed patients
Pregnancy
Acute hepatitis C

PREVENTION
No vaccine or immunoglobulin
Safe sexual practices
Avoiding sharing toothbrushes, razors, eating utensils.
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HEPATITIS B VIRUS
In thalassaemia major : HBsAg positive varies from <1%
to >20%, and past infection rates range from <10-70%

HBV marker :
Acute : HBsAg (4-5 mo), HBeAg (1-3 mo)
Chronic : HBsAg, anti - HBc
Previous infection or vaccination : antibody for HBsAg,
with anti HBc (prev. inf), or without anti
HBc(vaccination)
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Natural history :
Acute hepatitis : incubation periode 4-20 weeks
Progression to chronic hepatitis B : 5-10% in healthy
adults, and 90% in neonates
Cirrhosis : 1-2,2 % per year
Hepatocellular carcinoma

PREVENTION
Hep B Vaccine: 3 times (at 0, 1 and 6 mo), and booster
Hep B vaccine and HBIg to neonates delivery by a carrier

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TREATMENT
Lamivudin (3 TC)
Recombinant -interferon

HUMAN IMMUNODEFICIENCY VIRUS (HIV)
Prevalence in thalassaemia : <1% - > 20%
Management :
Antiretroviral therapy
Erythropoetin
Caution for drug that can exacerbate neutropenia
Control of iron overload
splenectomy
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CYTOMEGALOVIRUS
Treatment : Bone Marrow Transplantation
Leucoreduction of blood product

PARVOVIRUS B 19
May cause transient aplastic crisis
Characterized by :
A fall in Hb 2 g/dl or more
Reticulocytes < 0,2%
Absence of red blood precursors in the bone marrow
B 19 DNA viraemia reach up to 10
14
virious/ml
Transient drop lymphocytes, neutrophils, platelet

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Treatment :
Blood transfusion : acute B19 crises
Immunoglobulin administrations : chronics illness

MALARIA AND CHAGAS DISEASE
Plasmodium sp and Trypanosoma cruzii remain viable
in refrigerator blood components at least 2 weeks
Prevent transmission through blood product.
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IRON ASSOCIATED INFECTION
Bacterial Infections : Yersinia anterocolica, Klebsiella sp,
E. colli, Strept. Pneumonia, Pseudomonas aeroginosa,
Listeria monocytogenes

YERSINIA ENTEROCOLITICA
Lives in an iron rich environment
Transmitted by : ingested of contaminated food, meat,
water.
Mortality rate among recipient > 50%

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Clinical manifestations :
Severe in thalassaemia
Fever, abvdominal pain, diarrhoea, or vomiting
Athralgia, skin rashes
Complications : abdominal abscess, nephritis, splenic
abscess

Laboratory diagnosis
Culture from stool, blood, samples of affected tissue (e.g.
gut, lymph node)
Serial IgG titres

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TREATMENT
Stop iron chelation therapy immediately
Obtain suitable laboratory samples
Antibiotic treatment
Ciprofloxacin
Gentamycin
Chloramphenicol
Trimethoprim-sulfomethoxazole
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Table 1. Clinical and laboratory evaluation checklist
Monthly
CBC

Every 3 months
serum feritin
clinical chemistry
glucose
urate
creatinine
iron
TIBC
alk. Phosphatase
- GT
ALT/GPT
AST/GOT
LDH
Every 6 months
cardiac evaluations
cardiac echo
EKG
heart chamber
dimensions
systolic function
diastolic function
Fractional shortening
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Table 1. Clinical and laboratory evaluation checklist
Yearly
Virology
Hep C panel ( anti-
HCV, anti-HCV RIBA )
Hep B panel (HBsAg,
anti HBs, anti HBc Ig)
anti HIV 1+ 2

liver biopsi

endocrine function
evaluation
free T
4
and TSH
parathyroid hormone
FSH
LH
testosterone
estradiol
DHEA-S
fasting a.m. cortisol
OGTT
bone age and density
zinc, cooper,
selenium,
Vit C, vit E

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Table 1. Clinical and laboratory evaluation checklist
Yearly
complete physical exam
opthalmology
examination
audiology examination

As Indicated
24 hour Holter monitor
Cardiac stress test ( EST)
anti HBc Ig M
anti HBe
HBeAg
anti HDV
HCV - RNA

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INSERTION OF
DESFEROXAMINE
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post splenectomy
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