This document discusses thalassemias, which are hereditary disorders involving reduced synthesis of one or more globin polypeptide chains. It is classified into alpha and beta thalassemias. Alpha thalassemia involves defective synthesis of alpha globin chains, while beta thalassemia involves reduced beta chain synthesis. The classification ranges from severe homozygous forms like hydrops fetalis to mild heterozygous forms like thalassemia minor. The clinical features, laboratory findings, and treatment approaches are described for different forms of alpha and beta thalassemias. Prevention can be achieved through antenatal screening and diagnosis.

1. BY
M.SARASJOTHI
81 batch vz

2. DEFINITION
Thalassaemias are the heterogeneous group of
hereditary disorders in which there is reduced rate
of synthesis of one or more of the globin
polypeptide chains.
Quantitative abnormalities of polypeptide globin
chain synthesis.
Genetically transmitted.

5. GENETIC CONCEPT
Individuals inherits:
 2α globin genes-located one each on 2 chromosome
16
2β globin genes –locate one each on chromosome 11
EG:- normal adult haemoglobin HbA

12. CLASSIFICATION OF
THALASSAEMIAS
αTHALASSAEMIA βTHALASSAEMIA
 hydrops foetalis βThalassaemia major
HbH disease βThalassaemia
Thalassaemia trait intermedia
βThalassaemia minor

13. DEPENDING ON CHARACTERS
TWO TYPES OF THALASSAEMIA
 HETEROZYGOUS STATE [α and β thalassaemia
minor or trait]- generally asymptomatic
 HOMOZYGOUS STATE [α and β thalassaemia
major]-congenital haemolytic

14. α THALSSAEMIA
CAUSE: inability to synthesis adult haemoglobin.
MOLECULAR PATHOGENESIS:
 defective synthesis of α – globin chains
results in decreased production of Hb contains α
chain (i.e)HbA,HbA2,HbF.
 due to deletion of 1 or more α chain genes
located on short arm of chromosome 16

15. CLASSIFICATION
Depending upon the number of gene deleted,
 4 α gene deletion –Hb bart’s hydrops foetalis
3 α gene deletion- Hb H disease
2 α gene deletion- α thalassaemia trait
1 α gene deletion- α thalassaemia trait( carrier)

17. Hb BART’S HYDROPS FOETALIS
Deletion of all 4 α chain genes it results in total
suppression of α globin chain synthesis –most severe
form of α
thalassaemia
Hb BART’s is a gamma globin chain tetramers γ4 which
has high o2 affinity leading to severe tissue hypoxia

18. CLINICAL FEATURES
Incompatible with life due to severe tissue hypoxia
Fatal in utero or infant dies after birth
Alive –severe Rh haemolytic disease

20. LABORATORY FINDINGS
Infant born alive
 anaemia severe (Hb <6g/dl)
 blood film:
anisopoikilocytosis,hypochromia,microcytosis,pol
ychromasia,basophilic stippling,numerous
normoblast,target cells
 reticulocyte increase
Serum bilirubin increase
Haemolobin electrophoresis 80 -90%
HbBART’s,small amount hb H,hb portland but no

22. HbH DISEASE
deletion of 3α chain genes
HbH- β globin chain tetramer (β4)
Markedly impaired αchains synthesis.
HEINZ BODIES-HbH precipitated within RBC
Elongated α chain variants of HbHdisease termed as
Hb constant spring

23. CLINICAL FEATURES
Well compensated haemolytic anaemia
Intermediate between beta thalassaemia minor and
major
Anaemia severity flactuate –fall to very low in
pregnancy or infection
Splenomegaly and cholelithiasis

24.  HEPATOSPLENOMEGA
LY

25. LAB FINDINGS
Anaemia moderate Hb 8-9g/dl
Blood film:microcytosis
,hypochromic,basophilic,taret cells
,normoblast,stippling
Reticulocyte mild
Heinz body in mature red cell with brilliant cresol
blue stain
Hb electrophoresis:2-4%HbH remains
HbA,HbA2,HbF

27. α thalassaemia trait
 deletion of two of 4 α chain genes in homozygous
form homozygous α thalassaemia or
double heterozygous form heterozygous α
thalassaemia
Deletion of single αchain gene called heterozygous α
thalassaemia

28. CLINICAL FEATURES
Asymptomatic
Suspected in patient of refractory microcytic
hypochromic anaemia in whom iron deficiency and
beta thalassaemia minor have been excluded and the
patient belongs to high risk of ethnic group.
One gene deletion is silent carrier state.

29. LAB FINDINGS
Hb normal or mild decreased
Blood film:microcytic,hypochromic red cells but no
evidence of haemolysis or anaemia
MCH,MCV,MCHC are slightly decreased
Hb electrophoresis:small amount of HbBART’s in
neonatal period which gradually disappears by adult
life,HbA2 slightly decreased

31. βTHALASSAEMIA
CAUSE:decreased rate of β chain synthesis resulting
in reduced formation of HbA in red cells.
More complex than alpha thalassaemia
SYMBOLS:β-complete absent of synthesis
 β+ partial synthesis

32. IMPORTANT EFFECTS ON IT
BY

 transcription defect in promotor region result in β+
 translation defects in coding segment cause
termination results in βo
mRNA splicing defect cause abnormal mRNA ,may be
βo or β+

34. TYPES
Depending upon its extend of defect ,
 homozygous form: β thalassaemia major
 β thalassaemia intermedia
 heterozygous form: β thalassaemia minor

36. β THALASSAEMIA MAJOR
Also as Mediterranean or cooley’s anaemia
Most common form of congenital haemolytic
anaemia
Either complete or partial absence of β synthesis
Results in excess formation of HbF(α2,γ2) and HbA2
(α2,δ2)

38. CLINICAL FEATURES
Anaemia appears within 1st 4-6 months of life when switch
over from γ chain to βchain production occurs
Hepatosplenomegaly results in red cell
destruction,extramedullary haematopoiesis,iron overload
Hyperplasia
Iron over load due to repeated blood transfusion cause
damage to endocrine organs –growth decrease,delayed
puberty,DM,damage to liver ,heart.

40. LAB FINDINGS
Anaemia severe
Blood film: same as in alpha thalassaemia
S.bilirubin unconjugated increase
Reticulocytosis present
Blood indices decreased
WBC increased
Platelets normal or decrease with splenomegaly
Osmotic fragility decreased

41. TREATMENT
Regular blood transfusion(4-6 weeks)Hb ↑ 8g/dl

Folic acid increases demand of hyperplastic marrow
Children over 6 yrs –splenectomy
Prevent and treatment for iron over load br chelation
therapy
RISK:require multiple blood transfusion may cause
AIDS,myocardial siderosis leading to cardiac
arrhythmias,congestive heart failure,therefore death

43. β THALASSAEMIA INTERMEDIA
β thalassaemia of intermediate degree of severity that
does not require regular blood transfusion .these
cases are genetically heterozygous(βo/β or β+/ β)

44. β Thalassaemia minor
Mild asymptomatic in which there is moderate
suppression of β globin synthesis
CLINICAL FEATURES:asymptomatic
 diagnosis when patient is investiated for mild
chronic anaemia
Spleen palpable

46. LAB FINDINGS
Anaemia mild:mean Hb level 15% lower than normal
Blood film:mild
anisopoikilocytosis,microcytosis,hypochromia,occational
taret cells,basophilicnstippling
S.bilirubin normal or slightly raised
Reticulocytosis often +
Blood indices slightly reduced
Osmotic fraility decreased
Hb electrophoresis:confirmatory and shows 2-folds
increase in HbA2 and small elevation in HbF(2-3%)

47. TREATMENT
No any treatment
Explain about enetic implication of disorders
particularly to child bearing age
Eg; if 2 β thalassaemia trait married results in 25% of β
thalassaemia major in offsprings
 patients with βthalassaemia minor have normal life
span who mistaked and diagnose so treat for iron
deficiency anaemia which developes siderosis, and
complication

49. Few uncommon globin chain
combination resulting in trait
δβ-thalassaemia minor- total absence of both δ and β
chain synthesis –HbF↑
Hb lepore syndrome characterised by non
homologous fusion of δ and β enes formin an
abnormal haemohlobin called Hb Lepore.there is
total absence of β chain synthesis,

50. PREVENTION OF THALASSAEMIA
Possible by making an
 Antenatal diagnosis and this is done by chorionic
villous biopsy or
 Cells obtained by amniocentesis and
DNA studied by PCR amplification technique for
presence of genetic mutations of thalassaemia

54. THAN Q