Thalassemia

BLOK HEMATOLOGI DAN LIMFATIK

RINI PF
Basic Features
Thalassemia syndromes are characterized
by varying degrees of ineffective
hematopoiesis and increased hemolysis.
Clinical syndromes are divided into α-
and β-thalassemias, each with varying
numbers of their respective globin genes
mutated
b-Thalassemia
1. b0-Thalassemia: No detectable β-chain
synthesis due to absent β-chain messenger
RNA (mRNA)
2. b+-Thalassemia: Reduced β-chain
synthesis due to reduced or nonfunctional
β-chain mRNA
3. db-Thalassemia: δ- and β-chain genes
deleted
4. Eb-Thalassemia: Hemoglobin E (lysine
→glutamic acid at 26) and β-chain genes
deletion
5. Hb Lepore: A fusion globin due to
unequal crossover of the β- and δ-globin
genes (the globin is produced at a low
level because it is under δ-globin
regulation).
α-Thalassemia
1. Silent carrier a-thalassemia: Deletion of one α-
globin gene
2. a-Thalassemia trait: Deletion of two α-globin genes
3. Hb Constant Spring: Abnormal α-chain variant
produced in very small amounts, thereby mimicking
deficiency of the gene
4. HbH disease: Deletion of 3 α-globin genes, resulting
in significant reduction of α-chain synthesis
5. Hydrops fetalis: Deletion of all 4 α-globin genes; no
normal adult or fetal hemoglobin production.
β-Thalassemia

Pathogenesis

1. Variable reduction of β-chain synthesis (β0,

β+, and variants)
2. Relative α-globin chain excess resulting in
intracellular precipitation of insoluble
α-chains
3. Increased but ineffective erythropoiesis with many red
cell precursors prematurely
destroyed; related to α-chain excess
4. Shortened red cell life span; variable splenic
sequestration.
Sequelae

1. Hyperplastic marrow (bone marrow expansion with cortical

thinning and bony abnormalities)
2. Increased iron absorption and iron overload (especially with
repeated blood transfusion), resulting in
a. Fibrosis/cirrhosis of the liver
b. Endocrine disturbances (e.g., diabetes mellitus, hypothyroidism,
hypogonadism, hypoparathyroidism, hypopituitarism)
c. Skin hyperpigmentation
d. Cardiac hemochromatosis manifesting as pericarditis,
arrhythmias, cardiomegaly, pericarditis, and ultimately, cardiac
failure
3. Hypersplenism
a. Plasma volume expansion
b. Shortened red cell life (of autologous and
donor cells)
c. Leukopenia
d. Thrombocytopenia.
Hematology
1. Anemia: Hypochromic, microcytic
2. Reticulocytosis
3. Leukopenia and thrombocytopenia (may
develop with hypersplenism)
4. Blood smear: Target cells and nucleated
red cells, extreme anisocytosis, contracted
red cells, polychromasia, punctate
basophilia, circulating normoblasts
5. 51Cr-labeled red cell life span reduced
(but the ineffective erythropoiesis is more
important in the production of anemia)
6. Hemoglobin F raised; hemoglobin A2
increased
7. Bone marrow: May be megaloblastic (due
to folate depletion); erythroid hyperplasia
8. Osmotic fragility: Decreased
9. Serum ferritin: Raised.
Biochemistry
1. Raised bilirubin (chiefly indirect)
2. Evidence of liver dysfunction (late, as
cirrhosis develops)
3. Evidence of endocrine abnormalities, for
example, diabetes (typically late),
hypogonadism (low estrogen and
testosterone).
Clinical Features
Because of the variability in the severity of
the fundamental defect, there is a spectrum
of clinical severity (major to intermedia)
that considerably influences management.
β-Thalassemia intermedia is defined as
homozygous or doubly heterogeneous
thalassemia, which is generally not
transfusion dependent
1. Failure to thrive in early childhood
2. Anemia
3. Jaundice, usually slight; gallstones
4. Hepatosplenomegaly, which may be
massive; hypersplenism
5. Abnormal facies, prominence of malar
eminences, frontal bossing, depression
of bridge of the nose, and exposure of
upper central teeth
 a. Skull radiographs showing hair-on-end
appearance due to widening of diploic spaces
b. Fractures due to marrow expansion and
abnormal bone structure
c. Generalized skeletal osteoporosis
6. Growth retardation, delayed puberty, primary
amenorrhea in females, and other endocrine
disturbances secondary to chronic anemia and iron
overload
7. Leg ulcers
8. Skin bronzing
Complications
Complications develop as a result of:
● Chronic anemia in patients who are
undertransfused or in untransfused
thalassemia intermedia patients
● Chronic transfusion with resultant
hemosiderosis and hemochromatosis
● Poor compliance with chelation therapy
(generally).
Complications:
Endocrine disturbances (e.g., growth retardation,
pituitary failure with impaired gonadotropins,
hypogonadism, insulin-dependent diabetes
mellitus, adrenal insufficiency, hypothyroidism,
hypoparathyroidism)
Cirrhosis of the liver and liver failure
Cardiac failure due to myocardial iron overload
(often associated with arrhythmias and
pericarditis)
Extramedullary hematopoiesis, resulting in bony
deformities.
The causes of this include medullary expansion,
deficiency of estrogen and testosterone, nutritional
deficiency, and desferrioxamine toxicity.
Manifestations include rickets, scoliosis, spinal
deformities, nerve compression, fractures, and
severe osteoporosis.
Osteoporosis can be delayed by the early
institution of chelation in childhood and sex
hormone replacement early in adolescence.
Causes of Death
1. Congestive heart failure
2. Arrhythmia
3. Sepsis secondary to increased
susceptibility to infection post-
splenectomy
4. Multiple organ failure due to
hemochromatosis.
Supportive Care
1. Folic acid is not necessary in hypertransfused patients;
1 mg daily orally is given to patients on low
transfusion regimens.
2. Hepatitis B vaccination should be given to all patients.
3. Appropriate inotropic, antihypertensive, and
antiarrhythmic drugs should be administered when
indicated for cardiac dysfunction.
4. Endocrine intervention (i.e., thyroxine, growth
hormone, estrogen, testosterone) should be
implemented when indicated.
5. Cholecystectomy should be performed if
gallstones are present.
6. Patients with high viral loads of hepatitis
C that are not spontaneously decreasing
should be treated with PEG-interferon and
ribavirin.
7. HIV-positive patients should be treated
with the appropriate antiviral medications
8. Genetic counseling and antenatal
diagnosis (when indicated) should be
carried out using chorionic villus
sampling or amniocentesis.
9. Management of osteoporosis

 guidelines thalassemia
THAL B
Selamat Belajar