summary about Thalassemia from different resources

1. Thalassemia
Mohammed AlHinai

2. Thalassemia :
• a group of inherited hemoglobinopathies that characterized by absent or
reduced production of the alpha or beta chains used for assembly of the
hemoglobin molecule ( a quantitative defect in globin chain production).
Pathophysiology

3. B thalassemia

4. Types of B thalassemia
Beta thalassemia minor :
• Asymptomatic carrier
state.
Beta thalassemia major :
• Transfusion-dependent and
most severe form.
• Symptoms typically begin to
manifest during late infancy
around 5 to 6 months of
age.
Beta thalassemia intermedia :
• Non-transfusion-dependent.
• Less severe phenotype than major
as variable from asymptomatic into
presence of complication of
thalassemia.
• In certain cases develop
transfusion dependence later in life
during periods of erythroid stress :
- Pregnancy
- Infections
- Symptomatic anemia
- Develop extra-medullary
hematopoiesis with its
complication.
- Develop intra-medullary
hematopoiesis complication like
thalassemic fascia.
• develop some degree of iron
overload, due both to transfusions
and increased iron absorption
related to ineffective
erythropoiesis.

5. Clinical manifestation

6. Clinical features
Anemia :
• Occur as less Hb production, chronic hemolysis and other including aplastic crisis
• More severe in major thal which become symptomatic and require transfusion.
• Less severe in intermedia thal which usually asymptomatic but become symptomatic during
euthyroid stress.
• Symptoms include : looking pale, fatigue, weakness, chest pain, palpitation, SOB, dizziness, fainting.
• Long term complication of anemia including hepatosplenomegaly, pigment gallstones, heart failure
and arrhythmias, thrombosis, pulmonary abnormalities and pulmonary hypertension, leg ulcers.
Skeletal change and growth impairment:
• Occur by compensation of intra and extra-medullary
hematopoiesis to low Hb including :
- Facial deformity
- Change in body habitus as ribs and the bones of the
extremities becoming box-like and eventually convex,
and premature fusion of the epiphyses resulting in
characteristic shortening of the limbs, particularly the
arms.
- Osteopenia/osteoporesis which lead to fractures and
impaired growth.
- Bony masses as expansion of bone which behave
clinically like tumors, causing spinal cord compression
and other abnormalities.

7. Iron overload :
• result from a combination of ineffective erythropoiesis, which promotes increased intestinal iron
uptake and transfusional iron overload which cause :
- Growth impairement.
- Liver disease including cirrhosis.
- Endocrine and metabolic abnormalities like hypogonadism, hypothyroidism and insulin resistance
and diabetes.
- Heart failure and arrhythmias.

8. Diagnostic approach :
 Detailed history taking and physical examination.
 Laboratory test including :
• CBC with finding of :
- Low Hb
- High RBC count and might associated with low retics.
- Low MCV (microcytic), low MCH (hypochromic)
- Normal RDW (that differentiate from IDA)
• Peripheral blood smear :
- Microcytosis, hypochromasia,
- poikilocytosis, target cells and cell fragment.
• Other tests for hemolytic anemia as non-immune hemolysis with
high LDH, high indirect bilirubin, low haptoglobin and negative
coombs testing
• LFT, RFT, blood cross matching as baseline.
• Iron studies for differentiate from IDA :
- Serum ferritin will be in IDA and high in thal.

9.  Confirmatory tests:
• HPLC ( high performance liquid chromatography) :
- Increased HbF.
- Increased HbA2
• Molecular test based on genetic sequences (gold standard).

10. Differential diagnosis

11. General management
General measure :
• Educate the patient and family
about thal and premarital
screening.
• Obtaining steady state
laboratory value as baseline
• Nutrition :
- Folic acid 1 mg oral
supplement daily and multi-
vitamin.
• Routine evaluation for any
complication
Cure of thal :
• Bone marrow
transplantation.
Management of complication:
• Treat anemia by blood
transfusion (discussed next
pages).
• Treat of iron overload.
• Splenectomy if associated
with symptomatic
hypersplenism.

12. Blood transfusion
Decision to initiate regular transfusions
Transfusion as needed during :
• Pregnancy
• Infections
• Symptomatic anemia as
hemolysis or other causes.
In case develop any of
these symptoms, start
with regular transfusion
Next step

13. Amount of blood transfusion
Target of hemoglobin :
• Hb To be more than 9g/dL due to :
- maintain good cardiovascular status.
- exercise tolerance.
- at least partially suppress ineffective erythropoiesis.
Every week, there will be drop approximately 1g/dL of Hb. If we want to maintain the Hb above 9 g/dL at
end of month, should be transfused until reach Hb about 13 or 14 g/dL (as 4 weeks with each one need 1
g/dL). But the post-transfusion hemoglobin level should not exceed 14 to 15 g/dL or increased Hb by
5g/dL during transfusion due to risks of hyperviscosity.
Amount of blood by equation :
• 1 PRBC increased Hb by 1 g/dL :
- So we need about 5g/dL to increased
Hb from 9 into 14 g/dL which need
about 5 PRBC of blood transfusion.
Amount of blood by equation (more
accurate) :
• (amount of Hb you want to
increased) X weight X 4
- (14-9) X 50Kg(as example) X 4 = 1000
ml of blood
OR

14. Iron overload treatment
Decision to initiate chelation therapy

15. Target of iron :
• Ferritin less than 1000 mcg/L.
• LIC <7 mg Fe/g dry weight.
• cardiac T2* by MRI >20 milliseconds.
Choice of iron chelators depend on multiple factors which are variable
Raised of liver enzyme

16. Monitoring of iron overload by :
• Serum ferritin (every 3 months)
• Liver iron concentration by MRI (annually)
• Cardiac T2 by MRI (done if high result of previous tests)

17. Routine monitoring