Transcript Thalassemias Part One

MLAB 1415: Hematology
Keri Brophy-Martinez
Thalassemia:
Part One
1
Overview

Diverse group of congenital disorders which manifest as
anemia of varying degrees.
◦ Can be either homozygous or heterozygous
inheritance

Result of quantitative defective production of one or
more globin portion(s) of hemoglobin molecule.
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The decreased globin production causes
◦ Imbalanced globin chain synthesis
◦ Defective hemoglobin production
◦ Damage to the RBC
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Thalassemia Distribution
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Thalassemia
Results in overall decrease in amount of
hemoglobin produced and may induce
hemolysis.
 Two major types of thalassemia:

◦ Alpha (α) - Caused by defect in rate of
synthesis of alpha chains.
◦ Beta (β) - Caused by defect in rate of synthesis
in beta chains.

May contribute protection against malaria.
4
Review of Hgb Structure

Normal globin genes
◦ Alpha, beta, delta, gamma
 Form hgb A (97%), hgb A2(2-3%), hgb F (2%)
◦ Epsilon, zeta: in utero
◦ Gamma: 3rd trimester until birth
◦ Adult hemoglobin composed two alpha and two beta chains

Thalassemia causes an excess or absence of one of
these chains
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Pathophysiology: Beta Thalassemia
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α-chain excess
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unstable
Precipitates within the cell, causes damage
Macrophages destroy the damaged RBCs in
the bone marrow, leads to ineffective
erythropoiesis
Spleen also removes damaged RBCs, leads to
chronic extravascular hemolysis
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Pathophysiology: Alpha Thalassemia

β-chain excess
◦ Unstable
◦ Combines to form hgb molecules with 4 βchains (Hemoglobin H)
 Infants: excess gamma chains combine with
hgb molecules (Hemoglobin Bart’s)
◦ High oxygen affinity, poor transporter of oxygen
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Clinical and Laboratory Findings Associated with Thalassemia
Clinical Findings
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Comparison of Hemoglobinopathies
and Thalassemias
Disease
RBC
count
Hemoglobinopathy
Indices
RBC Morph
Abnormal
Hb
Ancestry
Normocytic
Target cells,
sickle cells
(HbS),
Crystals
(HbC)
HbS,HbC,
HbE etc
African
Mediterranean
Middle Eastern
Asian
Target cells,
basophilic
stippling
HbH
Hb Bart’s
African
Mediterranean
Asian
Normochromic
Thalassemia
Microcytic
Hypochromic
Retic
Count
Thalassemia: globin chains structurally normal
Hemoglobinopathies: globin chain is abnormal
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Beta
Thalassemia
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Classical Syndromes of Beta
Thalassemia
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Beta thalassemia minima/ Silent
carrier state – the mildest form of beta
thalassemia.
Beta thalassemia minor - heterozygous
disorder resulting in mild hypochromic,
microcytic hemolytic anemia.
Beta thalassemia intermedia - Severity
lies between the minor and major.
Beta thalassemia major - homozygous
disorder resulting in severe transfusiondependent hemolytic anemia.
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Beta Thalassemia Minor
Caused by heterogenous mutations that affect
beta globin synthesis.
 Usually presents as mild, asymptomatic
hemolytic anemia
 Have one normal beta gene and one mutated
beta gene.

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Beta Thalassemia Minor
Anemia usually mild
 Rarely see hepatomegaly or
splenomegaly.
 Have high Hb A2 levels

◦ 3.5-8.0%
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Normal to slightly elevated Hb F
levels.
Different variations of this form
depending upon which gene has
mutated
Normally require no treatment.
Iron deficiency anemia. Should be
ruled out
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Beta Thalassemia Major/ Cooley’s
anemia

Severe microcytic, hypochromic anemia.
◦ Severe anemia causes marked bone changes due to
expansion of marrow space for increased
erythropoiesis.
◦ See characteristic changes in skull, long bones, and
hand bones “hair on end”
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Detected early in childhood- 6 months- 2 yrs.
Hb A production is reduced
 HbA2 and Hg F production increased
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Clinical Findings:
β-Thalassemia Major
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Infants
◦ Irritability, pallor, failure to thrive
◦ Diarrhea, fever, enlarged abdomen
Severe anemia
Cardiac failure
Bronze pigmentation of skin
Bone changes
◦ Bossing of skull, facial deformities,
“hair-on-end” appearance of skull
Hepatosplenomegaly
Laboratory Findings:
β-Thalassemia Major
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Hb can be as low as 2–3 g/dL
Microcytic hypochromic
◦ MCV < 67 fL, ↓ MCH and MCHC
Peripheral blood smear
◦ Anisocytosis and poikilocytosis
◦ Basophilic stippling, polychromasia
◦ NRBCs
◦ ↑ RDW
β-Thalassemia Major
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Treatment
◦ Regular transfusions
 Minimize anemia
 Suppress ineffective erythropoiesis
◦ Iron-chelating agents
 Reduce excess iron absorption
◦ Splenectomy
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Prognosis
◦ Untreated – die during 1st or 2nd decade
◦ Hypertransfusion with iron chelation
 Extend for ≥ 1 decade
Hereditary Persistence of Fetal
Hemoglobin (HPFH)
Rare condition
characterized by continued
synthesis of Hemoglobin F
in adult life.
 Do not have usual clinical
symptoms of thalassemia.
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Kleihauer-Betke stain useful
tool to identify
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References
•
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Harmening, D. M. (2009). Clinical Hematology and
Fundamentals of Hemostasis. Philadelphia: F.A Davis.
McKenzie, S. B., & Williams, J. L. (2010). Clinical Laboratory
Hematology. Upper Saddle River: Pearson Education, Inc.