1. Thalassemia is a heterogeneous group of inherited disorders characterized by decreased synthesis of the alpha or beta globin chains of hemoglobin A, leading to ineffective erythropoiesis and hemolysis. 2. Beta-thalassemias result from reduced or absent beta chain synthesis and include beta-thalassemia major (severe transfusion dependent anemia), beta-thalassemia intermedia (severe anemia but not transfusion dependent), and beta-thalassemia minor (asymptomatic with mild anemia). 3. Laboratory findings in beta-thalassemia major include severe anemia, peripheral blood changes, increased HbF and HbA2 on electroph

1. Dr. B.V.Vydehi M.D
PROFESSOR OF PATHOLOGY
NARAYANA MEDICAL COLLEGE,NELLORE
THALSSEMIA

2. Adult hemoglobin - 96% HbA (2 2)
• Adult Hb is tetramer of 2 -chains & 2
-chains encoded by;
- Pair of -globin genes on chr. 16
- Single -globin gene on chr.11
2
2
2
 2
Hemoglobin Synthesis

3. •Heterogeneous group of inherited disorders
characterized by decreased synthesis of
either  or -globin chain of HbA (2 2) leading
to
- Low Intracellular hemoglobin
(Hypochromia)
- Relative excessive of unimpaired globin
chains  Ineffective erythropoiesis & Hemolysis
Thalassemias

4. • Most Frequent in Mediterranean,
African, or Asian Populations
• -Thalassemias :  Chain Synthesis
(100 different causative mutations)
• -Thalassemias :   Chain Synthesis
Deletions are more common (SE Asians)
Thalassemias

5. • Diminished synthesis of structurally
normal -globin chains, coupled with
unimpaired synthesis of  chains which
aggregate into insoluble inclusions within
RBC & their precursors 
Ineffective erythropoiesis & Hemolysis
 -Thalassemias

8. 1. Thalassemia Major : Severe transfusion
dependent anemia
i) Homozygous 0 – Thalassemia (0/0)
ii) Homozygous + - Thalassemia (+/+)
2. Thalasemia intermedia : Severe anemia but not
transfusion dependent
- Heterozygous with one - Thalassemia gene &
one normal gene : (+/ or 0 /)
3. Thalassemia minor : (- Thalassemia trait):
Asymptomatic with mild or absent anemia
- Heterozygotes, milder variants (+/ or 0 /)
 -Thalassemias-Syndromes

9. 

o o
+ +
No  Chain
Synthesis
Severe  
Chain
Synthesis
Severe Anemia
Chromosome 11
 - Thalassemia Major



10. i) Promoter region mutations :
Transcription defect:
- + Thalassemias (Some normal -globin
is synthesized)
ii) Chain terminator mutations :
Translation defect: Premature termination of mRNA
translation
- 0 Thalassemia (Prevention of -globin
synthesis)
iii) Splicing mutations : Most Common:
Both + & 0 Thalassemias occur
 -Thalassemias -Molecular Pathogenesis

11. • Anemia manifests 6 to 9 months after
birth, as Hb synthesis switches from HbF to
HbA
• Marked erythroid hyperplasia 
Expansion of bones Facial bone
deformity ( Mongoloid facies/Thalasemia
facies ) & malocclusion of jaw
• Extramedullary hematopoiesis involving
liver, spleen & lymphnodes  massive
enlargement
• Iron overload (Repeated blood transfusions
&  absorption of dietary iron) 
Hemosiderosis involving mainly heart, liver
& pancreas
 -Thalassemia-Major Clinical Features

19. 1. Anemia usually severe (Hb 3 to 6
gm/dl)
2. Peripheral blood :
Marked anisocytosis with
predominant microcytes, severe
hypochromia, basophilic
stippling, plenty of target cells &
nucleated RBC
3. Reticulocytosis
4.  MCV, MCH & MCHC
 -Thalassemia Major-Laboratory Findings

20. 5.  Serum bilirubin (Unconjugated)
6. Osmotic fragility – Decreased
( resistant to saline hemolysis)
7. Bone marrow : Erythroid(Normoblastic)
hyperplasia / Increased iron stores
8.Hb electrophoresis :
-Increased HbF & HbA2
-complete absence or small amounts of
HbA
 -Thalassemia Major- Laboratory Findings

21. 



o 
+ 
  chain
synthesis
  chain
synthesis
Mild or no anemia
 - Thalassemia Minor
(Asymptomatic -Thalassemia trait)

22. Laboratory Findings :
• Mild anemia
• Peripheral blood :Microcytosis & hypochromia,
occasional target cells
• Mentzer index:MCV/RBC >13 indicates IDA ; < 13
in Thal.minor
• MCV, MCH & MCHC – Reduced
• Hb electrophoresis : Confirmatory; Increase in
HbA2 to 4 to 8% of total Hb (Normal 2.5
%); HbF- N or slightly
 - Thalassemia Minor
(Asymptomatic -Thalassemia trait)

24. 1. Differentiation from hypochromic,
microcytic anemia of Iron deficiency
(serum Iron, TIBC & Ferritin estimation)
2. Genetic counseling
For individuals (Women of child bearing
age) at risk for both Thalassemia trait &
Iron deficiency Hb electrophoresis gives
confirmatory diagnosis
 - Thalassemia Minor
Importance of Recognition of -Thalassemia trait:

25.  - Thalassemias - Classification



Silent carrier
  


Chromosome 16
Hb Bart
or
HbH disease
(severe anemia) (Hydrops fetalis/lethal in utero)
 - thalassemia trait
(+/- anemia)

26. • Hb Barts: -Globin chain tetramer (4)
: High oxygen affinity  severe tissue
hypoxia
• Fatal in utero or infant dies shortly
after birth
• Severe anemia with microcytic,
hypochromic picture
• Hb electrophoresis : 80-90 % Hb-Barts
& small amounts of Hb-H & Hb-
Portland; No HbA, HbA2 or HbF
Hb Barts-Hydrops Fetalis