Thalassemia & Hemolytic anemia Flashcards
What is thalassemia?
The Thalassemia’s are the most common inherited abnormalities of haemoglobin. The disorder is typically characterized by a quantitative defect in the synthesis of either the alpha or beta globin chain.
What is alpha thalassemia?
➢The alpha thalassemia are a group of hereditary anaemias characterized by reduced or absent production of one or more of the alpha globin chains which made up the human haemoglobin.
➢It varies in clinical severity depending on the number of affected alpha globin chain.
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Epidemiology
➢The alpha thalassemia is common throughout parts of the world where malaria is endemic. It has been shown that the presence of both single and double alpha globin gene deletions confer some protection against malaria .
➢Occurs in individuals of all ethnic backgrounds. High prevalence in Saudi Arabia, India and Thailand . 20-30% in some parts of West Africa, 5-10 % in Mediterranean region.
Pathophysiology of Alpha thalassaemia
➢Alpha thalassaemia is caused by deficient expression of 1 or more of the 4 alpha globin genes on chromosome 16 leading to absent or reduced synthesis of alpha globin chains.
➢ This results in relative excess of gamma globin chains ( fetuses and newborns) and beta globin chains (children and adults).
➢Excess gamma and beta chains form tetramers termed haemoglobin Bart and haemoglobin H respectively.
➢These tetramers though soluble than alpha4 tends to precipitate and form inclusion bodies that damage the red cell membrane.
➢Reduced haemoglobinization of the red cells result in the destruction of the erythroid precurssors in the bone marrow (ineffective erythropoiesis) and hypochromia ,microcytosis of circulating rbc.
Different forms of Alpha thalassaemia
➢Broadly classified into 2, whether the loss of the alpha globin gene is complete, Hb Barts(alpha 0) or it is partial, alpha (+).
➢Alpha (+) sub classified into 3 depending on the number of gene affected.
I.Silent carrier . Inherit 3 normal alpha globin genes. (-α/αα).
II.Alpha thalassaemia trait. Inherit 2 normal alpha globin genes. (-α/-α) or (αα–).
III.Haemoglobin H disease. Inheritance of 1 normal gene.(-α/–).
Male and Female are always eequally affected by Alpha Thalassemia T/F
False
Male and Female are equally affected except for ART-X syndrome(Alpha thalassaemia that is associated with mental retardation) that affect only males.
Clinical features of Alpha Thalassemia
➢This varies according to the number of alpha globin chains deleted.
➢Hemoglobin Bart’s ,Hydrops Fetalis Syndrome ( Alpha thalassaemia major) (–/–)
I.Usually die in utero or shortly after birth because they are unable to make functional haemoglobin.
II.Total body oedema due to severe anaemia, congestive heart failure.
III. Hepatomegaly due to heart failure and extramedullary haemopoiesis.
IV.Numerous nucleated red blood cell on the blood film.
Haemoglobin H
•Chronic haemolytic anaemia.
•Neonatal jaundice and anaemia.
•Hepatosplenomegaly.
•Leg ulcers.
•Gallstones.
•Frontal bossing and overgrowth of the maxilla.
•Osteopenia and fracture.
Alpha thalassaemia Trait & Silent Carrier
Alpha thalassaemia Trait
•Usually asymptomatic.
•Normal complete blood count.
•Microcytosis ( MCV < 80fl ), hypochromia (MCH < 27pg) .
• Target cell usually seen on blood film.
➢Silent Carrier.
•Essentially asymptomatic.
•Complete blood count, MCV,MCH and peripheral blood film is normal.
Treatment and Management of Alpha Thalassemia and adverse effects of treatment
•Mild forms of Alpha thalassaemia may not require specific treatment.
•Patient with severe anaemia may require a life long transfusion therapy.
•Iron Chelation. Iron overload is a major problem in patients with Hb H and rare surviving Hb Barts.
•Every child who is maintained on a high-transfusion regimen ultimately develops iron overload and dies of siderosis of the myocardium.
• Chelation therapy should commence by the time the serum ferritin level reaches approximately 1000 g/dl. In practice, this level usually is seen after the 12th to 15th units transfusion.
•Infants must not be over chelated when the iron burden is still low in order to prevent toxicity.
•Folic acid supplementation in patients with haemolytic episodes and high bone marrow turnover rate.
•Splenectomy in patients with symptoms of hypersplenism.
•Bone Marrow Transplantation is seen as curative.
What is Beta Thalassaemia?
Beta Thalassaemia is usually caused by point mutation or rarely by deletions in the Beta globin gene on chromosome 11 leading to reduced (Beta+) or absent (Beta0) synthesis of the Beta chains of haemoglobin.
•Mode of inheritance is usually Autosomal recessive , though very few dominant mutations have been reported.
•Distribution- common in a broad belt ranging from the Mediterranean, parts of North and West Africa through the middle East and Indian sub-continent to SE Asia.
Pathophysiology of beta thalassemia
The reduced amount Beta + or absence Beta 0 of Beta globin chains result in a relative excess of unbound α globin chains that precipitates in erythroid precursors in the bone marrow leading to their premature destruction and hence ineffective erythropoiesis.
Types of Βeta- thalassaemia
1.Βeta- thalassaemia trait/ Minor/ heterozygous carrier.
Clinical features:
- Asymptomatic patient.
- Mild hypochromic microcytic anaemia.
- Raised HbA2 level. Usually > 3.5%
2.Beta thalassaemia– Intermedia/ B⁺
C/F:
- Moderate anaemia.
- Hepatosplenomegaly.
- features of Fe overload.
- Beta –thalassaemia Major
C/F :- Hypochromic, microcytic red cells, target cells.
- Cooley’s anaemia.
- Raised Hb A2 ( α₂δ₂).
- Raised Hb F (α₂ γ₂)
- Hepatosplenomegaly
- Thalassaemic/ mongoid facies.
- High serum Fe which may accumulate in the liver, myocardium or liver.
- Prone to infection.
- Hair on end appearance of the skull x-ray.
- Delayed secondary sexual development and short stature
- Leg Ulcer.
- Jaundice
- Pallor.
- Bossing of the skull
DIAGNOSIS of Beta Thalassemia
Peripheral Blood Film shows-
•Marked hypochromia,microcytes, nucleated red cells, Heinz bodies and target cells.
• WBC and platelets may be normal
•Increased reticulocyte count
•Increased HbF and HbA2.
•High performance liquid chromatography. (HPLC)
Prevention / Treatment of Beta Thalassemia
Genetic counseling
➢Regular blood transfusion.
➢Prevetion of Fe overload, using chelating agents, desferrioxamine or deferiprone.
➢ Folic acid.
➢Bone marrow transplatation.
➢Splenectomy in case of hypersplenism. Patient must be vaccinated against S. pneumoniae, H.influenzae, N. meningitidis pre-operatively and be put on maintenance dose of oral penicillin indefinitely.
