Download Chapter 1

MLAB 1415: Hematology
Keri Brophy-Martinez
Chapter 11:
Thalassemia
1
Overview

Diverse group of congenital disorders which
manifest as anemia of varying degrees.

Result of quantitative defective production of
one or more globin portion(s) of hemoglobin
molecule.

The decreased globin production causes
◦ Imbalanced globin chain synthesis
◦ Defective hemoglobin production
◦ Damage to the RBC

Distribution is worldwide.
2
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.
 May be either homozygous defect or heterozygous
defect.

3
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 of one of
these chains
4
Pathophysiology

α-chain excess
 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
5
Pathophysiology con’t
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
6
Clinical and Laboratory Findings Associated with Thalassemia
Clinical Findings
8
Comparison of Hemoglobinopathies
and Thalassemias
Disease
Hemoglobinopathy
RBC
count
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
Normochromi
c
Thalassemia
Microcytic
Hypochromic
Retic
Count
Thalassemia: globin chains structurally normal
Hemoglobinopathies: globin chain is abnormal
9
Beta
Thalassemia
10
Classical Syndromes of Beta
Thalassemia




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.
11
Beta Thalassemia Minor
Caused by heterogenous mutations that affect
beta globin synthesis.
 Usually presents as mild, asymptomatic
hemolytic anemia unless patient in under stress
such as pregnancy, infection, or folic acid
deficiency.
 Have one normal beta gene and one mutated
beta gene.

12
Beta Thalassemia Minor
Anemia usually mild
Rarely see hepatomegaly or splenomegaly.
Have high Hb A2 levels (3.5-8.0%) and normal to
slightly elevated Hb F levels.
 Are different variations of this form depending
upon which gene has mutated.
 Normally require no treatment.
 Make sure are not diagnosed with iron
deficiency anemia.



13
FIGURE 11-11 Patients with β-thalassemia minor show minimal morphologic abnormalities to include microcytosis
with target cells. The CBC in this patient showed the following results: Hb 11.1 g/dL; RBC count 5.2 x 10 12/L; MCV 61
fL; MCH 20.2 pg; MCHC 33 g/L. (Wright-Giemsa stain; 1000x magnification)
β-thal Minor – microcytic, occ
codocyte, basophilic stippling
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

Detected early in childhood
Hb A production is reduced
 HbA2 and Hg F production increased

16
Clinical Findings:
β-Thalassemia Major

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-onend” appearance of skull

Hepatosplenomegaly
FIGURE 11-8 Increased erythropoiesis in the bone marrow of patients with β-thalassemia major expands the marrow cavity
producing the typical “hair-on-end” appearance as seen on this radiograph of the skull of a boy with β-thalassemia.
Laboratory Findings:
β-Thalassemia Major
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
FIGURE 11-9 Peripheral blood smear from a patient with β-thalassemia major showing marked anisopoikilocytosis.
Target cells, schistocytes, teardrops, and ovalocytes are the major poikilocytes observed. An NRBC is also present.
(1000x magnification; Wright-Giemsa stain)
β-Thalassemia Major

Treatment
◦ Regular transfusions
 Minimize anemia
 Suppress ineffective erythropoiesis
◦ Iron-chelating agents
 Reduce excess iron absorption
◦ Splenectomy

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.
Kleihauer-Betke stain useful tool to identify
22