• The two α chains in HbA are encoded by an identical pair of a-globin genes on chromosome 16
  • The two β chains are encoded by a single β-globin gene on chromosome 11
  • Thalassemia is inherited as Autosomal recessive
  • Thalassemia is caused by inherited mutations that decrease the synthesis of either the α-­globin or β-globin chains of HB
  • Usually caused by deletions of one or more of the 4 alpha globin genes
  • Hepatosplenomegaly & edema No change in the proportions of hemoglobins A, A2, and F on Hb electrophoresis
  • Basophilic stippling is absent
  • In alpha-thalassemia trait,electrophoresis shows Normal HbF and normal HbA2
Hydrops fetalis--/-- Tetramers of excess γ globin chains (Barts Hb)Very high affinity for O2Invariably leads to IUD without transfusion
Hemoglobin H disease--/-αMost common in Asians Tetramers of excess β globin
(HbH)High affinity for O2, resemble thalassemia intermedia with moderately severe hemolytic anemia
Usually do not need transfusions except during crises
MCV is low (60-70 fL)
Reticulocyte count is elevated and RBC count is normal or elevated
HbH forms inclusions in erythroblasts and precipitates in circulating RBC
--/αα or -α/-αα-Thalassemia-1 trait Similar to β-thalassemia mino
MCV is low (60-75 fL)
Acanthocytes (cells with irregularly spaced spiked projections
) Reticulocyte count and iron parameters are normal.
Silent carrier -α/ααα Thalassemia-2 trait No red cell abnormality
  • Caused by point mutations that diminish the synthesis of B-globin chains
  • β0 mutations: absent β-globin synthesis
  • β+ mutations: reduced (but detectable) β-globin synthesis
  • Splicing mutations(Defect in Snurps causes): Most common cause of β+ thalassaemia
  • Normal levels of free Erythrocyte Protoporphyrin
  • Promoter region mutations: also associated with β+ thalassaemia
  • Chain terminator mutations: Most common cause of β0 thalassemia
  • ↓ synthesis of structurally normal β chains coupled with increased production of α chains
  • Imbalance between α- and β-globin synthesis Unpaired chains precipitate within red cell precursors → membrane damage → apoptosis à ineffective erythropoiesis
Clinical features
  • Anemia manifests 6 - 9 months after birth as Hb synthesis switches from HbF to HbA
  • Ineffective erythropoiesis Increased absorption of dietary iron secondary hemochromatosis (hemosiderosis)
  • Extramedullar hematopoiesis Frontal bossing, prominent facial bones (chipmunk facies) and dental malocclusion, hepatosplenomegaly
Lab features
  • Microcytic hypochromic anemia, anisocytosis, poikilocytosis
  • Target cells, basophilic stippling, nucleated red cells (normoblasts)
  • MCV, MCHC, MCH and TIBC decreased
  • Osmotic fragility decreased
  • Haptaglobin levels are decreased
  • Serum iron, ferritin and % saturation of transferring are increased
  • Bone marrow hypercellular, myeloid: erythroid ratio reversed
  • Hb electrophoresis is the gold standard investigation
  • X-ray shows crew hair cut appearance and hair on end appearance of skull bone
  • NESTROFT (Naked Eye Single Tube Red cell Osmotic Fragility Test) is used for screening
  • Test for 13- thalassemia trait is HbA2
  • Transfusion dependent
  • Bone marrow transplantation offers curative therapy
  • Oral desferoxamine is the most appropriate drug used for chelation therapy in beta thalassemia major
β Thalassemia intermedia
  • Chronic Intracorpuscular hemolytic anemia
  • Transfusions needed during periods of stress or aplastic crises
β Thalassemia minor or Thalassemia trait(β+/β or β0/β)
  • Asymptomatic, mild or no anemia
  • No need for transfusions
  • Resistance against falciparum malaria
Features Normal Thalassemia minor Thalassemia intermedia Thalassemia major
HbA 97 - 99% 80 - 95 % 0 - 30% 0 - 10%
HbA2 1 - 3 % 4 - 8 % 0-10 4 - 10 %
HbF < 1% 1-5% 6-100% 90 - 96 %
Exam Question
  • Oral deferiprone is the most appropriate drug used for chelation therapy in beta thalassemia major
  • Splenomegaly, Target cells on peripheral smear,Microcytic hypochromic anemia are seen in thalassemia major
  • Hb-A2 estimation will be diagnostically helpful in a case of beta thalassemia trait
  • Hb H disease is a form of alfa thalassemia
  • Intracorpuscular hemolytic anemia is seen in Thalassemia
  • Defect leading to thalassemia lies in Haemoglobin
  • Thalassemia occurs due to Splicing mutation
  • In Beta thalassemia, there is Decrease in beta chain, increase in alpha chain
  • A2 concentration in thalassemia trait is >3 .5
  • The investigation done to establish the diagnosis of thalassemia is Hb-electrophoresis
  • NESTROFT test is used in screening of Thalassemia
  • In α-thalassemia there is No α-chain
  • Thalassemia gives protection against malaria
  • Bone marrow iron is increased in Thalassemia
  • Decrease in osmotic fragility cause hemolysis in Thalassemia
  • Test for 13- thalassemia trait is HbA2
  • Hair on end appearance is seen in X-ray skull in Thalassemia
  • Hepatosplenomegaly and edema all over body of new born leading to death is diagnosed to have α-thalassemia
  • Splenectomy is least useful in Thalasemia major
  • Normal levels of free Erythrocyte Protoporphyrin with hypochromic microcytic anemia, seen in Thalassemia
  • Haptaglobin levels are decreased in Thalasemia
  • Thalassemia is inherited as Autosomal recessive
  • In alpha-thalassemia trait,electrophoresis shows Normal HbF and normal HbA2
  • Defect in Snurps causes thalassemia
Don't Forget to Solve all the previous Year Question asked on Thalassemia