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Anemia:- Part 4 – Thalassemia, α-thalassemia and β-thalassemia, Discussion and Work Up

June 15, 2022HematologyLab Tests

Table of Contents

  • Thalassemia
        • Definition of thalassemia:
        • History of Thalassemia:
        • To understand thalassemia, we need to discuss and understand the structure of the Hemoglobin:
        • Genetic codes and normal hemoglobin:
        • Mechanism of Thalassemia:
        • Classification of the Thalassemia:
      • Thalassemia major:
      • Thalassemia Intermedia:
      • Thalassemia minor:
    • Alpha- thalassemia (α-thalassemia):
      • α-thalassemia minor:
      • α-thalassemia trait:
      • α-thalassemia major:
    • Beta-thalassemia (β-thalassemia):
        • Beta-thalassemia major:
        • Beta – thalassemia intermedia:
      • Another classification:
        • Summary of Thalassemia types:
        • Beta-thalassemia differential diagnosis:
        • Treatment of thalassemia major:
        • Alpha-thalassemia needs:
        • Screening and diagnosis of the thalassemia patient:
        • Summary of thalassemia:

Thalassemia

Definition of thalassemia:

  1. Thalassemia has inherited hemoglobinopathies resulting from the decreased production rate of one or more globin chains of hemoglobin. Or
  2. These are a heterogeneous group of genetic disorders resulting from the decreased synthesis of α or β chains of hemoglobin.

The decreased hemoglobin synthesis leads to:

  1. Decreased hemoglobin in the RBCs.
  2. Hypochromasia.
  3. Microcytosis.
  4. Variable degree of hemolysis.
  5. Also called Cooley’s anemia.

History of Thalassemia:

  1. Thalassemia derives from the combination of the Greek word Thalassa means sea, and Haima means blood.
  2. This was known as Mediterranean anemia because of the most common occurrence in the Mediterranean population.
  3. This is characterized by a decreased rate of production of globin chains.  These are classified according to the globin which is involved.
  4. The consequence is defective globin chain production.

To understand thalassemia, we need to discuss and understand the structure of the Hemoglobin:

  1. The normal globin, which is part of the hemoglobin, consists of 2 alpha and 2 beta chains.
Hemoglobin normal structure

Hemoglobin normal structure

Various types of hemoglobin and their structures:

Type of hemoglobin Genotype of hemoglobin Hemoglobin presence
Hb A α2β2 This is the main adult Hb
Hb A2 α2/δ2 This is present in a small amount
Hb F α2/γ2 Main fetal Hb in late stages
Hb gower1 ζ2/ε2 This Hb is present in the early life of the fetus
Hb gower2 α2/ε2 This Hb is present in a small amount in the early fetal life
Hb portland ζ2γ2 It is seen in embryos.
Hb H β4 It is seen in α-thalassemia
Hb Bart’s γ4 It is seen in α-thalassemia
  1. Each pair is inherited from each parent.
    1. So one α/β gene is inherited from the father and the other α/β pair from the mother.
Hb-gene locus encoding

Hb-gene locus encoding

  1. In thalassemia, a gene may involve either α or β chains.
  2. In the majority of the patients, β-chain is involved.
  3. HbA1 has 2 α and 2 β-chains.
  4. HbA2 has 2 α and 2 δ-chains.
  5. HbF has 2 α and  2 γ-chains.
  6. All these hemoglobin HbA1, HbA2, and HbF are present in the adult RBCs.
  7. HbA2 and HbF are present in trace amounts.

Genetic codes and normal hemoglobin:

  1. The genes located on chromosomes 11 are γ, δ, ε, and β-chains.
  2. While on chromosome 16, there are 2 α and ζ loci.
  3. β-thalassemia:
    1. In heterozygous conditions, only one of the β-chain is involved, called β-thalassemia minor.
    2. In homozygous conditions, both β-chains are involved, called β-thalassemia major.
  4. α-thalassemia:
    1. α-chain involvement is more complicated.
    2. Because there are 2 α-gene loci on chromosome 16 while the β-gene is only one locus on chromosome 11.
    3. In silent carries of α-thalassemia, only one of the 4 α-genes (1/4) is absent (deleted or abnormal).
    4. In α-thalassemia minor, 2 of the 4 α-genes (2/4) are affected. There may be deletion or abnormality in both gene loci.
    5. In α-thalassemia-1, which is more common in Asians.
    6. In α-thalassemia-2, which is more common in the African and Medittranians.
  5. HbH disease occurs because of the deletion or inactivation of the three gene loci (3/4). So all 4 globin chains are β-chains.
  6. Hb Bart’s disease is a more serious disease; it occurs when all the 4 α-genes (0/4) are deleted or inactivated. There are all 4 γ-globins.
Hemoglobin gene location

Hemoglobin gene location

Mechanism of Thalassemia:

  1. Thalassemia syndrome may occur because of the abnormality of:
    1. Coding sequence.
    2. Transcription.
  2. Processing or defects in gene translation leads to thalassemia.

Classification of the Thalassemia:

  • The older classification was classifying thalassemia based on the severity of the disease as follows:

Thalassemia major:

  1. α-globin genes are absent (0= –/–).
  2. Hb Bart’s at birth is 75%.
  3. MCV = 110 to 120 fl.
  4. MCH is greatly decreased.
  5. This is also called hydrops fetalis.
  6. Signs and symptoms:
    1. The complete absence of the α-globin genes in the fetal life leads to intrauterine death of the fetus due to severe hypoxemia.
      1. This is due to Hb Bart’s, which has a high affinity for oxygen, and prevents the release of O2 to the tissues.
    2. At birth, no S/S.
    3. Infants during 3 to 6 months show pallor, yellow skin, and sclera.
    4. Infants during 6 to 12 months show severe anemia, bone abnormalities, and cant thrive.
    5. There are life-threatening complications.
    6. There is splenomegaly or hepatomegaly.
    7. These patients will have frequent infections.
    8. There is a tendency for bleeding, like a nose bleed.
    9. These patients have a small body, but the large head is a characteristic feature.
    10. These infants may be mentally retarded.

Thalassemia Intermedia:

  1.  There is some degree of anemia, jaundice, and splenomegaly.
  2. There are signs of hemosiderosis, such as hemoptysis.
  3. There is iron deficiency anemia.

Thalassemia minor:

  1. One globin gene is absent (-α/αα).
  2. These are the silent carrier.
  3. There are usually no symptoms.
  4. There is mild anemia.
  5. MCV is normal to slightly decreased.
  6. HbH small amount of 1% to 2% may be present at birth. This will disappear later on.
  7. Often these patients are overlooked.

Thalassemia minima:

  1. It is a mild disease.
  2. It is a silent carrier of the β-thalassemia trait.
  3. Anemia is not evident.
  4. HbA2 = normal or slightly increased. HbF is increased.
  5. Normal RBC morphology and Hb electrophoresis.

The second classification of thalassemia:

  1. It is based on the genetic makeup of the hemoglobin, and it is divided into:
    1. α-Thalassemia.
    2. β-Thalassemia

Alpha- thalassemia (α-thalassemia):

  1. α-thalassemia is a group of genetic disorders with defective α-chain synthesis.
    1. Chromosome 16 carries 2 α genes, and the total number of α-gene is 4.
      1. Severity depends upon the patient’s affected number of genes one, two, three, or four.
    2. Decreased synthesis of α-chain will decrease the synthesis of HbA, HbF, and HbA2 because these chains have α-chains; the net result will be an excess of β-chains and γ-chains. These chains may polymerize to form tetrameric forms γ4 called Hb Bart’s, and β4 called HbH.
      1. These abnormal Hb Bart’s and HbH are the characteristics of α-thalassemia.
    3. Usually manifested immediately after birth or even in utero because the α-gene is activated early in fetal life.
    4. α-thalassemia has a wide range of clinical presentations.
    5. Chromosome 16 carries 2 α genes, and the total will be 4 α-genes (each pair from the parents). This will vary the severity of the diseases, depending upon one: two, three, or four genes affected in one patient.
    6. Another feature of α-thalassemia is that decreased or absent α-gene production will result in more than γ-chain during fetal life and at birth and excess of β-chain later on. This will lead to stable tetramers,  γ4 (Hb Bart’s) and β4 (Hb H).  Hemoglobin Bart’s and H precipitate in the older RBCs. These may lead to hemolytic crises by infection. This abnormal hemoglobin can be detected by electrophoresis.
Thalassemia-alpha mechanism and events

Thalassemia-alpha mechanism and events

α-thalassemia minor:

  1. These are silent carriers.
  2. There is decreased production of the α-chain (α+-α / ββ).
  3. One α-globin gene is affected = -α/αα.
  4. These are the silent carrier, and there is no marked anemia.
  5. MCV will be normal to decrease slightly.
  6. Hb H (1% to 2%) is present at birth and disappears later.

α-thalassemia trait:

  1. It has  2 α-globin genes affected = α-/α- or αα/–.
    1. RBCs show microcytosis and hypochromic anemia.
    2. MCV is <70fl.
    3. There is mild anemia.
    4. Serum electrophoresis showed 5% to 10% Hb H (4 β) at birth, which will disappear later.

α-thalassemia major:

  1. It is Hb H disease.
    1. Three α-globin genes are affected = α-/–.
    2. There is microcytic hypochromic anemia.
    3. MCV is <70 fl.
    4. Serum electrophoresis showed predominantly Hb Bart’s, consisting of 4 gamma chains at birth.
      1. There is a gradual shift to Hb H 5% to 30% over the first few months of life.

Alpha-thalassemia Characteristic features:

Clinical features Genotype structure Electrophoresis pattern Peripheral blood smear
Normal person αα/αα
  1. Normal at birth
  2. Normal at adult
  1. Normal picture
  2. MCV = 85 to 95 fl
  3. MCH = 28 to 32 pg
α-Thalassemia carrier (silent carrier) 3 -α/αα
  1. Normal at adult
  2. Hb Bart’s = 1% to 3%
  1. Normal picture, asymptomatic
  2. MCV = 74 to 88 fl
  3. MCH = 24 to 28 pg
α-thalassemia trait (α-thalassemia minor) 2 -α/-α   or  –/αα
  1. Hb Barts’ = 4% to 10% at birth
  2. HbA2 Normal/decreased in adult
  1. Mild hyperchromasia   and microcytosis
  2. MCV = 65 to 78 fl
  3. MCH = 20 to 24 pg
α-thalassemia major (Hb H disease) 1 –/-α
  1. At birth = Hb Bart’s 10% to 25%
  2. At adult = HbH = 10% to 25%
  1. Severe hypochromasia and microcytosis, and Heinz bodies
  2. MCV= 59 to 72 fl
  3. MCH = 17 to 21 pg
Hydrops fetalis (Hb Bart’s disease) 0 –/– At birth=, Hb Bart’s (γ4) 75%
  1. Severe hypochromasia and microcytosis
  2. MCV = 110 to 120 fl
  3. MCH = Markedly decreased

α-thalassemia classification and characteristic features:

The genotype of α-thalassemia Severity of anemia Hb at birth Hb at adult α-chain deletion  Clinical outcome
α-thalassemia carrier
Normal picture     1 Asymptomatic
α-thalassemia 1 trait Hypochromic ± Hb Bart’ 5% to 10% Hb A, A2, and F 2
α-thalassemia 1/α-thalassemia 1 (Hydrops) Hypochromic +++ Hb Bart’s 80% Trace of HbH and Portland 4 Incompatible with life
α-thalassemia 2/trait Hypochromic ± Hb Bart’s 1% to 2% HbA, A2, and F 1
α-thalassemia 1/α-thalassemia 2 (HbH) Hypochromic ± and inclusions

Hb Bart’s 1% to 15%

 

HbB 4% to 30% 3
  1. Clinical features of alpha-thalassemia:
    1. In case of loss of all 4 α-genes, it is incompatible life and leads to the fetus’s death (hydrops fetalis).
Alpha-Thalassemia leading to hydrops fetalis

Alpha-Thalassemia leading to hydrops fetalis

    1. Microcytic hypochromic anemia with splenomegaly. This is known as Hb H disease because of the Hb H (β4) presence. Can find this Hb on electrophoresis.
    2. In fetal life, Hb Bart’s is seen.
    3. α-Thalassemia trait is caused by the loss of one or two α-genes that are not usually associated with anemia, but MCV and MCH are low.

Beta-thalassemia (β-thalassemia):

Beta-thalassemia major:

  1. This is also called Cooley’s anemia and is the homozygous state of β-thalassemia
  2. It consists of 2 α chains and 2 γ-chains.
  3. There is decreased production of the β-chain (α2 / β0 β0). A globin gene mutation causes partial β-gene or total β-gene chain loss.
  4. The number of genes affected, partial or complete, will determine the severity of the disease.
  5. There is an increase in the production of γ-chains and δ-chains, resulting in an increased Hb F and Hb A2 levels.
  6. The β chain is replaced by the 2-γ chain, which will form Hb F, and the other is replaced by δ-chains, which will form Hb A2.
  7. These are usually homozygous (β0β0):
  8. β0β0-thalassemia is a more severe variant. No β-chains are synthesized.
  9. No Hb A found on electrophoresis.
  10. Only HbF (>90%) and HbA2 (3% to 8%) are found.
  11. This is also called Cooley anemia.
  12. There is marked microcytosis and hypochromasia.
  13. MCV is <70 fl and Hb is 2 to 3 g/dL.
  14. There is hepatosplenomegaly, bony deformities, and failure to thrive as an infant.
  15. These patients are dependent upon blood transfusion.
Beta-Thalassemia mechanism

Beta-Thalassemia mechanism and formation of HbF and HbA2

Beta – thalassemia minor:

  1. where a single β-gene is affected (β0/β).
    1. There is mild anemia Hb 9 to 11 g/dL  or no anemia.
    2. Normal to increased RBC count.
    3. RBCs are microcytes, MCV 60 to 70 fl.
    4. Electrophoresis shows a mild increase in the Hb F and Hb A2 (3% to 8%).

Beta – thalassemia intermedia:

  1. It is most commonly caused by partial deletion of β0 of both beta genes.
  2. These are homozygous (β+β+) genes.
  3. It will give a wide spectrum of the disease with moderate to severe anemia, and Hb will be 6 to 10 g/dL.
  4. There are growth retardation and bony abnormalities.
  5. This usually occurs later than the major thalassemia type.
  6. Electrophoresis shows Hb F 20% to 40% and increased Hb A2, 3% to 8%.
Thalassemia intermedia on electrophoresis

Thalassemia intermedia on electrophoresis

Another classification:

  1. β0+ shows a complete absence of the production of the beta chains.

    1. This is found in the Mediterranean, particularly in Northern Italy, Greece, Algeria, and Suadi Arabia. And Southeast Asia.
  2. β+-thalassemia is less severe.
    1. There are three groups of this gene rearrangement.
  3. 1β+ thalassemia gene produces less amount of the beta-chain, around 10% of normal production. This group is found throughout the Mediterranian region, middle east,  Indian subcontinent, and Southeast Asia.
  4. 2β+ thalassemia gene produces more of the beta-chain around 50% of the normal population. This is found in the blacks of North America and West Africa.
  5. 3β+thalassemia gene produces even more beta chains and gives rise to milder disease. It is found particularly in Italy, Greece, and the Middle east.
  6. Severe thalassemia is called thalassemia major.
    1. Sever hypochromic and microcytic anemia develops during the first year of life.
    2. Hemoglobin is <7 g/dL and consists mostly of HbF and HbA2.
  7. Homozygous type 2 and 3 beta+ causes a milder form of thalassemia called thalassemia intermedia.
    1. The heterozygous beta-thalassemia gene causes a milder form of anemia.
      1. This also shows mild hypochromasia and microcytosis called thalassemia minor.
    2. The minor group may show delta-chain abnormality.
  8. Beta-delta thalassemia (δβ)  is another rare form of thalassemia characterized by the combined defect in δ and β chain synthesis.
  9. This group may have a normal level of Hb A2 and usually a high level of Hb F in the heterozygote and absent Hb A and A2 in the homozygote.
  10. δβ-thalassemia can be divided into two groups according to Hb F found:
    1. If γ-gene is active, then that group is called GγAγδβ thalassemia.
  11. Another type that has inactive γ, δ, and β genes is called Gγδβ thalassemia.

Beta-thalassemia syndrome shows:

Type of β-thalassemia Genotype of β-thalassemia Characteristic features
β-thalassemia minor
  1. β / β+
  2. β / β0
  1. One abnormal gene
  2. Either there is β+ or β0
  3. Different patterns in electrophoresis
β-thalassemia major
  1. β / β0
  2. β+ / β+
  3. β+ / β0
  1. There are two abnormal genes
  2. Possibilities are β0β0, β+β+ or β0β+
  3. Patients are not anemic at birth but develop anemia within a year.
  4. The most common cause of death in childhood is infection.
  5. Electrophoresis shows increased HbF 50% to 95%, normal to a raised level of HbA2. Mostly HbA is not present.
  1. Clinical features of beta-thalassemia:
    1. In beta-thalassemia major, there is severe anemia, which appears 3 to 6 months after birth.
    2. The liver and spleen enlargement due to increased destruction of the RBCs, intramedullary hemopoiesis, and iron overload.
    3. Splenomegaly needs more blood and increases RBC destruction and pooling.
    4. Bone marrow hyperplasia in thalassemia leads to thalassemic face. There is thinning of the cortex of the bones, which may lead to bone fractures.
    5. X-rays may show the bossing of the skull and typically a hair-on-end appearance.
  2. Lab findings of beta-thalassemia:
    1. Low Hemoglobin.
    2. The peripheral blood smear shows Hypochromic and microcytic anemia.
    3. Hb electrophoresis confirms the diagnosis by the near absence of the decreased level of Hb A.
Hemoglobin electrophoresis of thalassemia

Hemoglobin electrophoresis of thalassemia

Hemoglobin on electrophoresis is different in different types of thalassemia.

Patient % of the type of Hemoglobin
Normal newborn
  1. Hb A = ≅ 25%
  2. Hb F = ≅ 75%
  3. Hb A2 = 1%
Infant 6 months of age
  1. Hb A = ≅ 85 to 90%
  2. Hb F = ≅ 10%
  3. Hb A2 = 2%
Normal adult
  1. Hb A = 96%
  2. Hb F  =  1%
  3. Hb A2 = 3%
Alpha thalassemia
  1. Silent carrier = Normal (-α/αα )
  2. Minor =  Normal (–/αα)
  3. Intermedia  (Hb H disease)= (–/αα)
    1. Hb A = 70% to 90%
    2. HbH 5% to 30%
Beta thalassemia
  1. Minor = (βo/β)
    1. Hb A ≅90%
    2. Hb A2 = 3% to 10%
    3. Hb F = ±
  2. Intermediate = (β+/β+)
    1. Hb A = 50% to 70%
    2. Hb A2 =3% to 8%
    3. Hb F = 20% to 40%
  3. Major = (βo/βo)
    1. Hb A = 0%
    2. Hb F = >90%
    3. Hb A2 = 3% to 8%

Summary of Thalassemia types:

  1. α-Thalassemia trait is due to double gene deletion.
    1. There are microcytes and hypochromasia.
  2. α-Thalassemia disease is due to three gene deletions.
    1. There are target cells, ovalocytes, microcytes, and Hb H inclusion in the RBCs.
  3. β-Thalassemia in heterozygotes, and there is β gene deletion alone or combined with the δ gene.
    1. There are microcytes, target cells, elliptocytes, and basophilic stippling.
  4. β-Thalassemia in homozygotes, and there is β gene deletion alone or in combination with the δ gene.
    1. It is marked as hypochromasia with polychromatic rims.  There are target cells, ovalocytes, basophilic stippling, and HbH crystals.
Beta-thalassemia smear

Beta-thalassemia smear

Beta-thalassemia differential diagnosis:

Characteristics Homozygous β-thalassemia Heterozygous β-thalassemia
Hemoglobin 2 to 5 g/dL 9 to 11 g/dL
RBC morphology
  1. Marked poikilocytosis
  2. There are target cells
  3. It is basophilic stippling
  4. There are nucleated RBCs
  5. There are Heinz bodies
  1. There are small hypochromic RBCs

 

Reticulocytes count ≥15% It is mildly elevated.
Platelets
  1. Low if splenomegaly is done
  1. Normal
WBC count
  1. It is low if there is splenomegaly.
  1. Normal
Bone marrow
  1. It is erythroid hyperplasia that leads to bone deformity.
  1. Mild to moderate erythroid hyperplasia
Hb A2 Variable 3.5 to 7%
Hb F 10 to 90%
  1. A mild increase in 50% of cases
Storage iron
  1. Greatly increased
  2. There is hemosiderosis
  1. Normal or slightly increased

Treatment of thalassemia major:

  1. These patients survive by blood transfusion. It is tried to maintain the hemoglobin levels over 10 g/dL.
    1. It usually requires 2 to 3 units every 4 to 6 weeks.
    2. Fresh blood, filtered to remove white blood cells, gives the best RBCs survival and fewer reactions.
    3. 500 mL of blood contains 250mg of iron.
  2. Regularly give the folic acid 5 mg/day.
  3. Iron supplements are contraindicated.
  4. Iron overload is a complication that needs chelating therapy to control iron overload.
    1. Deferoxamine is the most common drug used for the chelation of iron.
    2. This can be given 1 to 2 mg with each unit of the blood.
    3. Give 40 mg/kg subcutaneously over 8 to 12 hours, 5 to 7 days weekly.
    4. This should be started in infants after the 10- to 15 units of the blood transfusion.
  5. Excess iron causes skin pigmentation and damages the heart.
    1. Assessment of the iron status advises:
      1. Serum ferritin.
      2. Serum iron.
      3. % saturation of transferrin.
      4. Serum non-transferrin bound iron.
  6. Bone marrow biopsy for reticuloendothelial stores by Perl’s stain.
  7. Liver biopsy for parenchymal and reticuloendothelial stores.
    1. Assessment of the tissue damage  caused by the iron overload:
      1. For heart damage caused by iron, advice:
        1. X-ray chest.
        2. ECG, 24 hours monitoring.
        3. Echocardiography.
        4. Radionuclide scan to check left ventricular ejection.
      2. For liver damage by the iron advice:
        1. LFT.
        2. Liver biopsy.
        3. CT scan or MRI.
      3. For endocrine glands damage caused by iron, advice:
        1. Glucose tolerance test.
        2. Pituitary gonadotropin release test.
        3. Growth hormone assay.
        4. Radiology of the bones.
        5. Isotope bone density study.
        6. Functional tests of the thyroid, parathyroid, adrenal, and gonadal glands.
    2. Vitamin C 200 mg/day. This will help in the excretion of iron produced by deferoxamine.
    3. Immunization against the Hepatitis B virus.
    4. Allogenic bone marrow transplantation will give a permanent cure.
  8. Infections are quite common in these patients and need treatment by antibiotics.
  9. Treatment for β-thalassemia:
    1. This is supportive treatment.
    2. Antibiotics for infections.
    3. Folic acid supplement.
    4. Transfusion of packed RBCs to raise the hemoglobin.
    5. Splenectomy may be advised.
    6. Bone marrow transplantation may be done.

Alpha-thalassemia needs:

  1. Blood transfusion.
  2. In utero can give blood transfusion in case of hydrops fetalis.

Screening and diagnosis of the thalassemia patient:

  1. The peripheral blood smear is typical of microcytic and hypochromic anemia.
    1. In the case of homozygous β-thalassemia and double heterozygous non-α- thalassemia, peripheral smear shows:
      1. Severe anisocytosis.
      2. Poikilocytosis with bizarre shape.
      3. There are target cells.
      4. There are ovalocytes.
      5. There are numerous nucleated RBCs.
Thalassemia typical picture

Thalassemia typical picture (β-thalassemia major smear)

  1. In heterozygous β-thalassemia, peripheral blood smear shows:
    1. There are hypochromic microcytic RBCs with moderate anisocytosis and poikilocytosis.
    2. Basophilic stippling is also seen.
  2. MCV is the best screening for patients with thalassemia. There is decreased MCV, 85% chance if this is <75 fl (femtoliters).
  3. RBC count of >5 million/mm3.
  4. Hb level is <9 g/dL.
  5. MCHC <30%.
  6. Reticulocytes are increased in these patients. This is increased in:
    1. In Hb H, the disease may be up to 10%.
    2. In homozygous β-thalassemia may reach 5%.
  7. Normal RDW (red cell volume distribution width).
    1. The only exception of RDW in Thalassemia major is the degree of anisocytosis leading to an increased level.
    2. In iron deficiency, the RDW is increased, and the decrease in MCV is less striking.

Differential diagnoses of various anemias:

Type of anemia Serum iron TIBC Ferritin level  RDW Free RBC protoporphyrin A2 level
α-thalassemia Normal Normal Normal Normal Normal Normal
β-thalassemia Normal Normal Normal Normal Normal Increased
Iron-deficiency anemia Decreased Increased Decreased Increased Increased Normal
Chronic diseases anemia Decreased Decreased Increased Normal Increased Normal
  1. In heterozygous thalassemia, MCH is <22 pg, MCV <70 fl, and Hb is around 9 to 11 g/dL.
  2. Cord blood can be used to diagnose thalassemia.
  3. DNA analysis of chorionic villus sample at 8 to 10 weeks of pregnancy.
  4. Or Amniotic fluid cells by amniocentesis at 16 to 18 weeks.
  5. Serum electrophoresis of the infants.
    1. Electrophoresis plays an important role in diagnosing thalassemia, and it will detect an increased level of HbA2, HbF, and other abnormal hemoglobins (HbH and Bart’s).

The following table shows β-thalassemia hemoglobin on Hb-electrophoresis:

Type of thalassemia HbA HbA2 HbF
Normal infants 95% to 97% 2% to 3% 1% to 2%
β-thalassemia homozygous type Nil 2% to 5% 95% to 98%
β-thalassemia Heterozygous 90% to 95% 3.5% to 7% 2% to 5%
β+-thalassemia homozygous or double heterozygous β+/β0 5% to 35% 2% to 5% 60% to 95%
Heterozygousα δβ- thalassemia (Hb Lepore syndrome) 80% to 92% 1% to 2.5% 5% to 20%
Hereditary persistent HbF (HPHF) (homozygous) Nil Nil 100%
HPHF heterozygous African type 65% to 85% 1% to 2.5% 15% to 35%
HPHF heterozygous Greek type 755 to 85% 1.5% to 2.5% 15% to 25%

Summary of thalassemia:

Thalassemia summary

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