The Thalassaemias

The Thalassaemias Thalassemias- group of disorders in which normal Hb prodution is partially or completely suppressed and is charaterised by- reduced output of one or more of the chains secondary to mutation of globin genes. They are classified according to the particular globin chain that is ineffectively produced– the  and  thalassaemias are by far the most important ↓ .

Haemoglobin types involved- HbA - 2 2 HbA2 - 2 2 HbF - 2 2 HbH - 4 Hb Bart 4

 thalassaemia • Thalassaemia is associated with a wide spectrum of clinical severity. •  thalassaemia results from over 150 different mutations of  globin genes resulting in absence or reduction of the  globin chain and excess production of  chain. This results in destruction of the red cell precursors in the reticuloendo-thelial system causing severe anaemia (-thalassaemia major)

-Thalassaemia minor/TRAIT • thalassaemia minor or trait (heterozygous state): • This is a carrier state, and is usually asymptomatic. Mild, well-tolerated anaemia (Hb >9g/dL) which may worsen in pregnancy. • MCV <75fL, HbA2 >3.5%, slight HbF. Often confused with iron deficiency anaemia.

Thalassaemia Intermediasyndrome • Thalassaemia Intermediasyndrome • between these two extreme (major and minor) • Describes an intermediate state with moderate anaemia .There may be splenomegaly. • 60% present at the age of 2 years

Clinical features • -Thalassaemia major (60% present during infancy) • thalassaemia major (Cooley's anaemia) • Presents within the 1st year, with severe anaemia and failure to thrive. • Extramedullary haematopoiesis (production of RBCs outside the bone marrow) occurs in response to the anaemia, causing characteristic facial deformities eg skull bossing and hepatosplenomegaly (also due to haemolysis). • Skull x-ray shows ˜hair on end appearance due to increased marrow activity..

skull bossing

Thalassaemia intermedia syndrome (TIS) • Diagnostic features are variable, clinical manifestation of symptomatic anaemia, hepato-splenomegaly and bony changes – frontal bossing (haemolytic facies) occur after 2 years of age in contrast to -thalassaemia major which present during infancy. • Red cell indices, electrophoresis as in -thalassaemia major but haemoglobin level 6-8g/dl is maintained for a longer time. Transfusion required when Hb drops below 6g/dl

DIAGNOSTIC FEATURES OF BETA-THALASSAEMIA Major • Profound hypochromic anaemia • Evidence of severe red cell dysplasia • Erythroblastosis • Absence or gross reduction of the amount of haemoglobin A • Raised levels of haemoglobin F • Evidence that both parents have thalassaemia minor

Minor • Mild anaemia • Microcytic hypochromic erythrocytes (not iron-deficient) • Some target cells • Punctate basophilia • Raised resistance of erythrocytes to osmotic lysis • Raised haemoglobin A2 fraction • Evidence that one parent has thalassaemia minor

Management of T.major • Blood transfusion: The management of severe forms of -Thalassaemia entails a regularblood transfusion • Iron chelation therapy with overnight infusions of desferrioxamine (DFO) and a low dose of vitamin C 200 mg/day to prevent life threatening complication of iron overload

Regular transfusions to keep Hb>10 gm/dl is required. • Iron chelation therapy should be started when iron loading exceeds 1000 µg/dl

MANAGEMENT contd… • Supportive care - Cholelithiasis with manifestation of cholestasis and cholangitis need cholecystectomy • Gene therapy - Correction of underlying defect in gene in stem cells by normal gene. • Bone marrow transplantation (BMT) - giving a new haemopoitic system is the only curative procedure.

Splenectomy - isindicated in selected cases if hypersplenism present and there is no increase in Hb%inspite of blood transfusion. If it to be done prior Hib, pneumococcal and menigococcal vaccines are given. Prophylactic antibiotics should be given for life.

The Thalassaemias