Table of contents
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Thalassemia
- Introduction:
- Common in african americans and mediterraneans.
- Defects in production of various hemoglobin molecules.
- Genes:
- 4 α-globin --> 2 copies on chromosome 16 (x2 alleles)
- 2 β-globin --> 1 copy on chromosome 11 (x2 alleles)
- 2 γ-globin --> 1 copy (x2 alleles)
- 2 δ-globin --> 1 copy (x2 alleles)
- Types of Hemoglobin in RBC's:
- Fetal hemoglobin = HbF (2α, 2γ), switches to Adult at 3-6mo of life.
- Adult hemoglobin = HbA (2α, 2β) and HbA2 (2α, 2δ)
- Typically 97% is HbA, and ~3% is HbA2
-
HbA constitutes 97% of adult hemoglobin
-
HbA2 constitutes 3% of adult hemoglobin
- Thalassemia
- Defect in one or more Hb genes.
- Number of genes affected = severity of disease.
- Ineffective erythropoeisis (production)
- Intravascular hemolysis
- Divited into:
- alpha and beta thalassemia
- Chromosome 16: two duplicated copies of alpha-chain.
- Labs:
- Microcytic, hypochromic erythrocytes + target cells (targets look like vases)
- To distinguish from Iron Deficiency Anemia: Look at RDW:
- RDW is high in Iron Deficiency Anemia (large variety of sizes/shapes of RBC)
- RDW is normal in thalassemia.
- Can actually measure Mentzer Index (1973) MCV / Erythrocyte-count = ..
- > 13 = Iron Deficiency
- < 13 = Thalassemia (RBC count preserved, so lower ratio)
- Treatment:
- Can absorb iron well, can develop overload.
| Syndrome | e | Symptoms | Treatment |
|---|---|---|---|
| α-Thalassemia Silent (-α/αα) [1-gene deletion] | Medeterranean + African & SE Asia
(Also, Middle- Eastern) | Asymptomatic, clinically silent. | None |
| α-Thalassemia Minor (-α/-α) or (--/αα) [2-gene deletion] (2-3% of all blacks) | Asymptomatic, mild microcytic anemia, low MCV. Often mistaken for iron deficiency, but iron studies = normal. Electropheresis is normal! (no substitution happens) | None | |
| Hemoglobin H Disease (--/-α) "β4 tetramers" [3-gene deletion] | Mod-to-Severe Anemia, low MCV, splenomegaly Electropheresis: Detects HbH | Intermittent transfusion | |
| Hemoglobin Barts (--/--) [4-gene deletion] | Lethal in utero (Hydrops Fetalis) | In utero transfusion? | |
| β-Thalassemia Minor (- β) [1-gene deletion] | Medeterranean (also SE Asia, India, Pakistan) | Asymptomatic, mild microcytic anemia (Hb=90-140 g/L) (Hypochromia, target cells) - Electropheresis helpful --> instead of β chains, make δ and γ as substitution. - Shows increased HbA2 (α2δ2) and HbF (α2γ2) | None |
| β-Thalassemia intermedia (mild form of β-Thal Maj) | Moderate to severe anemia, iron overload - Severity depends on degree of β expression. | Intermittent transfusion, iron chelation | |
| β-Thalassemia major (- -) or (β°) [2-gene deletion] | Severe anemia, poor growth, skeletal abnormalities, iron overload. Hemolysis, underproduction, increased HbF. Hb = 40-60 g/L | - Lifelong Transfusions, - Iron chelation (deferoxamine), - Splenectomy to decr transfusion requirements - HSCT |
(Information to make this table came from MKSAP 16 from ACP).
Beta Thalassemia
- Types:
- Minor - Asymptomatic
- Intermedia - Mild anemia
- Major - SEVERE (poor growth, skeletal abnormalities, iron overload)
- Labs:
- Hemoglobin electrophoresis
- Hemoglobin A
- Hemoglobin A2 (elevated, diagnostic)
- Hemoglobin F (residual)
- Hemoglobin electrophoresis
- Low-level hemolysis typically occurs
- Generally deficient in folate
- (TODO: management)
Other Hemoglobinopathies
- Examples (there are hundreds!)
- Hemoglobin E (from SE Asia)- Heterozygous: Microcytosis.
- Hemoglobin E and B-Thal -> Variable based on mutations
- Hemoglobin C - Target cells, normal Hb.
- If inherited with Hemoglobin S (SC) - sickling occurs.
- Hemoglobin D
- HbDD or HbAD (homozygous or heterozygous) do not cause hemolysis
- Co-inheritance with S = sickling syndrome.
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