Thalassemia

Thalassemia: Impaired globin gene production

a globin b globin

b globin a globin

Hgb A tetramer

Globin chain synthesisa cluster - chromosome 16

b cluster - chromosome 11

2 2z e Gower 1

2 2z g Portland Embryonic

2 2a e Gower II

2 2a g F Fetal<1%

2 2a d A21.5-3.5%

Adult

2 2a b A>95%

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Thalassemia

• Organization of globin genes

• Decreased production of normal globin chains– thalassemia—deficiency of gene(s)– thalassemia—deficiency of gene(s)

12

12

G A

G A

cluster - chromosome 16 cluster - chromosome 11

Alpha Thalassemia: Clinical Features

• Absence of 1–2 alpha chains – Common– Asymptomatic– Does not require therapy

• Absence of 3 alpha chains (Hgb H disease)– Microcytic anemia (Hgb 7–10)– Splenomegaly

• Absence of 4 alpha chains– Hydrops fetalis (non-viable)

1a2a

1a2a

1a2a

1a2a

1a2a

1a2a

XXX

XX

1a2a

1a2aXXX

1a2a

1a2aX XXX

Alpha Thalassemia: Laboratory Findings

ChainsHgb(g/dl)

MCV(fl) Hgb Analysis

/ Normal Normal Normal

/- 12–14 75–85 Normal

-/- or --/ 11–13 70–75Normal with Hgb Barts ( 4); Hgb H (4) (small)

-/-- 7–10 50–60Normal with Hgb Barts ( 4); Hgb H (4) (large)

--/-- - - Not viable

Hypochromic Microcytic RBCs: Alpha Thalassemia

Alpha thalassemia trait Alpha thalassemia (-/--)

Photomicrographs from American Society of Hematology Slide Bank

Beta ThalassemiaClinical syndrome

Genotype Hgb (g/dl) Hgb A2 Hgb F

Minor (Trait) + or ° 10–13 + +

Intermedia +/+ 7–10 + ++

Major (Cooley’s anemia)

+ or ° <7 + +++

Beta Thalassemia Major

Skeletal – Osteoporosis due to bone marrow expansion– Pneumatization of the sinuses is delayed by

expanded hematopoiesis• Dilated cardiomyopathy secondary to severe

anemia • Growth and development delayed• Hepatomegaly due to extramedullary

hematopoiesis

Microcytic Hypochromic Anemia:Beta Thalassemia Major

Approach to Beta Thalassemia

• thalassemia trait– Screening/counseling

• thalassemia intermedia/major– Screening/counseling– RBC transfusion therapy (+ iron chelation therapy)– Agents to increase hemoglobin F (hydroxyurea)– Bone marrow transplantation