Download MBBS (Bachelor of Medicine, Bachelor of Surgery) Pathology PPT 10 Hemolytic Anemia Thalassemia Lecture Notes
THALASSEMIA
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Pre -Lecture Feedback Questionnaire
Q 1. Have you ever heard about a disease
cal ed thalassemia?
a. I know it from TV
b. I heard on the radio
c. I read in the newspaper
d. I heard at school
e. I have a relative with this disease
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f. I know someone with this disease
g. I have a relative who is a thalassemia carrier
h. I have never heard
i. I learned from another source
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Q 2. If you have heard about thalassemia,
write what you know in a few sentences.
Q 3. Is this disease is inherited?
Yes, inherited
No
No idea
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Q 4. Do you know the importance of being a
carrier of these diseases?
a. I don't know
b. If you know, explain in few words
Q 5. Do you know if you are a carrier for
Thalassemia?
a. I don't know
b. Yes I am a carrier for Thalassemia
c. I am not a carrier for Thalassemia
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Q 6. Is it possible to identify carriers?
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What is the position of the
disease in India?
? India is the thalassemia capital of the world with 40
mil ion carriers and over 1, 00,000 patients.
? There is no prevention and control programme at the
national level.
? With preventive health checks not being the norm in
India, people suffering from thalassemia are
unknowingly passing on this genetic disorder to their
children.
? Over 1, 00,000 patients across the country die before
they turn 20 due to lack of access to treatment.
Ref: The Hindu report on Thalassemia in India
? Every year approximately 100,000 children
with Thalassemia Major are born world over,
of which 10,000 are born in India.
? It is estimated that there are about 65,000-
67,000 -thalassemia patients in our country
with around 9,000-10,000 cases being added
every year
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Ref: Indian Pediatr. 2007 Sep;44(9):647-8
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Learning objectives
? What is thalassemia?
? Molecular Pathology of thalassemia
? Pathophysiology of Thalassemia
? Classification of Thalassemia
? Clinical Presentation of Thalassemia
? Peripheral smear findings in Thalassemia
? How to diagnose a suspected case of
thalassemia
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THALASSEMIA
SYNDROME
Definition :Heterogenous group of inherited
disorders caused by genetic lesions leading
to decreased synthesis of either or ?
globin chain of Hb A
Deficient synthesis of ? chain- ? Thalassemia
Deficient synthesis of chain- Thalassemia
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GLOBIN SYNTHESIS:
Globin synthesis depends on two gene
clusters situated on
Chromosome -11 for ? globin chain
Chromosome -16 for globin chain
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MOLECULAR PATHOGENESIS
? ? Thassemia
? 1) ?0 ?Thalassemia, Total absence of ?
globin chain in homozygous state
? 2) ?+- Thassemia, Reduced ? globin
synthesis in homozygous state
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Promoter region mutations
Chain Terminator Mutations
Splicing Mutations
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5'
3'
Promoter
Exon 1
Exon 2
Exon 3
sequence
?+ Thal
?0 Thal
?+ Thal
Transcription defect
RNA splicing defect
Translation defect
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PATHOPHYSIOLOGY OF
THALASSEMIAS
? - Thalassemia is due to an m-RNA
abnormality this mutation reduces or
inhibit the production of - globin
chains.
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?Point mutation in or near the - globin
gene (Most Common) ?
i) Defective splicing (splice do not occur
or occur at wrong site)
ii) Stop codon ? non sense lesions
(chain terminate prematurely)
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? Frame shift mutation (insertion or
deletion of a single nucleotide,
resulting in lengthening or shortening
of DNA molecules)
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Patho - Physiology of
Thalassemia
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Precipitation
Hb F
Selective survival of Hb F containing
Extravascular
cells
# of RBCs Precursors
Hemolysis
within marrow
Splenomegaly
High O2 affinity of RBCs
Ineffective
Erythropoiesis
Tissue Hypoxia
Anemia
Erythropoietin
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Anemia
Tissue Hypoxia
erythropoietin
Blood
Transfusion
Marrow Expansion
Bone Deformity
Iron absorption
Metabolic Rate
Iron Loading
Gout
Folate Deficiency
Endocrine Deficiencies
Cirrhosis
Cardiac Failure
Death
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Clinical & Genetics Classification of
Thalassemias
Clinical
Genotype
Disease
Nomenclature
Thalassemia Homozygous thal
Severe
Major
(0/ 0)
+/ +
Thalassemia +/ + +/ 0 0/ Severe but doesn't
Intermedia
+/
require regular BT
Thal minor
0/ , +/
Asymptomatic
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Alpha Thalassemia
Clinical
Genotype
Disease
Nomenclature
a) Silent Carrier
- /
Asymptomatic
b) ? Thal trait
--/
Asymptomatic (like
Thal minor)
c) Hb. H disease
--/-
Severe
d) Hydrops fetalis
--/--
Lethal in uterus
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Clinical Presentation
? Children with thalassemia remains
asymptomatic till the age of 6 months.
? Mostly having symptoms related to anaemia
like Jaundice
Fatigue
Pallor
Shortness of breath
Delayed growth/puberty
Skeletal deformities
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Clinical Presentation contd..
? Organomegaly ? Hepatomegaly
Splenomegaly
Lymphodenopathy
Skull X-Ray: New bone formation on the
outer table producing perpendicular
radiations resembling a crew-cut
appearance.
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Peripheral smear findings
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marked poikilocytosis, anisocytosis, and
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polychromatophilia
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The signs of active normoblasts in erythropoiesis are in
3evidence:
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Howell-Jolly bodies, polychromatophilia, and 33
nucleated RBCs.
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nucleated RBC & Target cells
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basophilic strippling.
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acant
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es, spherocytes, target cell,and schistocytes.
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leptocyte and target cell.
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Reticulocytosis - demonstrated by new
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methylene blue stain
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? RBCs: marked poikilocytosis,
anisocytosis, and polychromatophilia.
? The predominant poikilocyte is the target
cell.
? The poikilocytes of hemolysis are also
seen: acanthocytes,
spherocytes,
burr cells, and schistocytes.
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? Moderate to marked basophilic stippling is
seen in both the nucleated and non-
nucleated forms of erythrocytes.
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lNucleated RBCs which are almost invariably
present are often numerous and may
outnumber the leukocytes.
lThe last two nucleated RBC stages, the
polychromic normoblast and orthochromic
normoblasts, are the predominant forms seen.
l Reticulocytosis is usually present and may
be quite high, e.g., 20% or greater.
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The signs of active erythopoiesis:
Howel -Jol y bodies,
polychromatophilia,
and nucleated RBCs.
? Leukocyte: Leukocyte counts range from
10,000-25,000/mm3, and occasionally present
immature form.
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METHODS FOR INVESTIGATION
OF THALASSEMIA
? Complete Blood Count (Rule of 3)
? HbA2 and Hb F, measurement by HPLC
? Molecular methods e.g, PCR for
mutational analysis.
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Management
? Haematopoietic stem cell transplantation
? Blood transfusion
? Chelation Therapy(Deforaxmine,Defriporone)
? Hydroxyurea
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Post-Lecture Feedback
Questionnaire
What are the main characteristics of
thalassemia?
What are the complaints of the patients?
What is the treatment?
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Q 2. Are the disease inherited?
a. Yes, inherited
b. No
c. I have no idea
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Q3. What is the impact of consanguineous
marriages on these diseases?
Q4. What is the impact of being a carrier of
these diseases?
Q5. Do you want to have a blood test to
learn if you are a hemoglobinopathy carrier?
a.Yes
b.No
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Q6. What is your opinion about the study?
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QN 1.Which ONE of the following is NOT a
feature of thalassaemia intermedia?
A) It may be due to homozygous
o thalassaemia
B) It may be associated with extramedullary
haemopoiesis
C) It is usually associated with splenomegaly
D) It may cause iron overload
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QN2. Which ONE of these statements is
TRUE about thalassaemia major?
? A. The major cause of death is liver failure
? B. It requires iron chelation at diagnosis
? C. It is usually caused by deletion of
globin genes
? D. It may be diagnosed antenatally
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QN3. Which ONE of the following
statements is TRUE about thalassaemia
trait?
A. It is associated with a raised haemoglobin
A2 level
B. It is associated with iron overload
C. It is associated with a reticulocytosis
D. It is associated with splenomegaly
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Points to be remember
? Most common cause of + Thalassemia
? Most common cause of 0 Thalassemia
? Thalassemia :MC type of mutation seen
? Thalassemia : MC type of mutation seen
? Role of Hydroxy urea in Thalassemia
? D/D of MCHC anemia
? Lab diagnosis of thalassemia
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This post was last modified on 07 April 2022