This document provides an overview of thalassemia, including definitions, types, clinical findings, and treatment. It discusses the differences between hemoglobinopathies and thalassemias. The main types covered are alpha and beta thalassemia. Alpha thalassemia affects alpha globin chain production and can range from asymptomatic to fatal. Beta thalassemia affects beta chain production and includes conditions such as beta thalassemia major, beta thalassemia intermedia, and beta thalassemia minor. Treatment involves regular blood transfusions for severe types and monitoring for mild types.

1. Thalassemia
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2. hemoglobin
- Adult Hb contains two α-chains and two β-chains.
- Globin and Heme.
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3. Hemoglobinopathy vs. thalassemia
 Qualitative deffect in the
structure of Hb resulting in
abnormal one.
 point mutation.
 usually normal Hb.
 Structural variant of
hemoglobin.
 Quanitative disorder of
Hb synthesis that produce
reduced amount of normal
Hb.
 Deletional & nondeletional
mutation.
 Reduced Hb and oxygen
caring capacity.
 Separate disease.
Hemoglobinipathy thalassemia
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4. Hemoglobinopathy vs. thalassemia
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5. Definition of thalassemia
- Mild genetic defects are asymptomatic.
- Severe genetic defects are symptomatic:
1. low Hb.
2. Increase in abnormal Hb.
3. Ineffective erythropoeisis.
4. Anemia = Hb + ineffective erythropoesis + hemolysis
5. Hepatosplenomegaly.
6. Infections.
7. Gallstones.
8. Bone deformities.
9. Chronic hemolysis.
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6. Clinical findings
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7. Types of Thalassemia
- Most common: α-thal (gene deletion) and
β- thal (promotor mutaytion, nonsense mutation
and stop mutaion)
- Reduction of δ synthesis doesn’t associated
with anemia (defected HA2 is rare ˜ 2.5%)
- Severe impairment of ζ , Ɛ or ɣ is lethal in utero.
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8. Common thalassemias
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9. Alpha Thalassemia
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10. α-thalassemia overview
CBC:
 slightly decreased or normal RBC’s count.
 decreased MCV,MCH and MCHC.
 increase in Reticulocytes number.
Chemistry:
 increased bibllirubin.
 inccreased haptoglobin.
Blood film:
 microcytic, hypochromic anemia.
 anisocytosis and poikelocytosis.
 basophilic stippling.
 NRBC’s.
 precipitated Hb.
B.M studies:
 not necessary.
 erythroid hyperplasia with basophilic stippling.
 seideroblasts.
 foam cells (severe form) 23/02/1441
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11. Alpha Thalassemia types
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12. 4-genes affected
 Hydrops fetalis.
 Stillborn or die within hours after birth.
 Electrophoresis: 80-90 % Hb bart’s.
10-20 % Hb Portland.
No HbA1 , HbA2 or HbF.
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13. 3-genes affected
 HbH disease.
 Symptomatic but not fatal.
 The severity depends on which allele is
affected in parents genotype.
 Electrophoresis: HbBart’s (at birth)
HbH (Adult)
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14. 2-genes affected
 α-Thalassemia minor.
 Asymptomatic (only diagnosed by gene analysis)
 Mild anemia (border line)
 Electrophoresis: 5-6 % Hb Bart’s (only after birth)
 Occasional cells exhibit HbH inclusions after
incubation with brilliant cresyl blue.
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15. 1-gene affected
 Sielent “carrier”
 Electrophoresis: 1-2 % Hb Bart’s (infant).
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16. Hb electrophoresis
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17. Affinity to oxygen by different
Hbs
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18. 23/02/1441
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19. β-thalassemia
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20. Classification of β-thalassemia
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21. β-thalassemis major
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22. β-thalassemis major
 Cooley’s anemia.
 Compensation by other Hb.
 Ineffective erythropoesis.
 Erythroid hyperplasia > 0.25
 Free α–chains contain free iron and chemichromes (ROS)
 Majority of hemolysis is st B.M (polychromatophilic
erythroblast)
 Extramedullary hematopoesis.
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23. β-thalassemis major in children
- Begins at 6th month of birth.
- Pallor, fuileir to thrive, gaining weight, diarrhae, and
fever.
- Groth retredation:
.characteristic bossing of the skull
.facial deformities
.“hair-onend” appearance of the skull
on x-ray
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24. Clinical findings of β-thalassemis
major
CBC:
 Microcytic hypochromic anemia, MCV< 67 fl.
 Hb is 2-3 g/dl.
 Normal /Increased RDW.
 2o Thrombocytopenia and leucopenia.
 Basophilic stippling and poly chromasia.
 Precipitated α-chains (methyl violet stain).
Chemistry:
 Elevated uncojugated billirubin (extravascular hemolysis)
 Dark brown urine.
Bone marrow:
Not necessary, M:E is 1:10 or less.
Molecular technique:
β-to-α chain ratio <0.25
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25. Electrophoresis
- From cord blood after birth
HbA is <2% , while
normal infant’s HbA is
20%
- For adults:
90% HbF
No HBA
Normal/abnormal HbA2. 23/02/1441
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26. β-thalassemia minor
- Sufficient Hb.
 Asymptomatic.
 Moderate microcytic RBC’s.
 Heteroappearance at stress ( pregnancy& infections).
CBC:
 RBC’s > 5X1012/L
 Reteciolocytes: slightly increased.
 Rare NRBC’s.
 Hb: 9-14 g/dl.
 MCV: 55-70 fL
 MCHC normal or slightly decreased: 29-33
 MCH: < 22 pg.
 Anisocytosis & poikelocytosis (basophilic stippling& target cells).23/02/1441
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27. β-thalassemia minor
Bone marrow:
 Slightly hyperplasia
 Erythroblasts poorly filled with Hb.
Electrophoresis:
 HbA2: 3.5-7 %
 HbF normal in 50% of cases.
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28. β-thalassemia intermedia
 Hb: 7-10 g/dl.
 Moderate microcytic, hypochromic anemia.
 Iron overload (in case of blood transfusion).
 Target cells are the predominant poikilocytes observed, Basophilic
stippling and nucleated red blood cells are also present.
Electrophoresis:
 HbA2: 5-10 %
 HbF: 30-75
 Milder forms of β-thalassemia intermedia is missy with minor β-Thal.
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29. β-thalassemia minima
- Asymptomatic.
- No CBC abnormalities.
- Discovered serendipitously during family studies.
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30. Other Thalassemias and
Thalassemia-Like Conditions
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31. Other Thalassemias and
Thalassemia-Like Conditions
δB-Thalassemia:
 Rare thalassemia, β- and δ-chains are affected.
 100% HbF in homozygous (thalassemia intermrdia phenotype and
anemia)
 Hetero form of the disease not anemic and looks like Thal minor.
Ɣδβ-Thalassemia:
 Rare thalassemia, deletion or inactivation of the entire β-gene complex.
 Homozygous form is incompatible with life due to absence of adult Hb.
 Heterozygous form is developed to mild form of β-thalassemia.
Hemoglobin Constant Spring (HbCS):
 Common in Thailand.
 combination of two structurally abnormal α-chains and two normal β-chains.
 Homozygous individual has two normal α-genes, one on each chromosome (α-
Thal minor) 23/02/1441
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32. Hemoglobin Constant Spring
(HbCS)
 Hb Bart’s at birth
 HbCS makes up 5–7% of Hb.
 HbA2 and HbF are normal
and the reminder is HbA
 HbCS (0.2–1.7%)
 Normal HbA, HbA2 and HbF.
Homozygotes Heterozygotes
* In some areas, the coexistence of HbCS with α-thalassemia trait (- -/aaCS) can be
found:
- The clinical findings are similar to those of HbH disease.
- Hemoglobin electrophoresis characteristically shows;
HbA, HbH, Hb Bart’s, HbA2, and 1.5–2.5% HbCS.
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33. Hereditary Persistence of Fetal Hemoglobin
(HPFH)
Incidence:
0.1% of African Americans.
Cause:
absence of δ- and β-chains synthesis or a loss of suppression of the ɣ-globin gene.
Homozygous:
 100% HbF and absence of HbA and HbA2
 Erythrocytosis ranging from 6 * 1012/L to 7 * 1012/L (higher oxygen affinity)
 high hemoglobin levels from 14.8–18.2 g/dL
 Erythrocytes are microcytic and slightlyh ypochromic MCV of 75 fL and a mean MCH of 25.0 pg.
Heterozygous Patients present:
 slightly elevated erythrocyte count.
 with the corresponding elevation of the hematocrit.
 Slightly decreased MCH (27 pg).
 HbF is 10–30% of the total hemoglobin.
 HbA2 is decreased to 1–2% and the remainder is HbA. 23/02/1441
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34. Hemoglobin Lepore
Cause
aberrant crossover event resulting in recombination of misaligned β- and
δ-genes on separate chromosomes.
Product:
 δ/β-fusion globin chain, two of which combine with two α-chains to form Hb Lepore, stable and
normally function,.
 Chromosome containing the β/δ-anti-Lepore fusion gene still contains intact β-and
δ-genes that are synthesized normally to form HbA and HbA2.
Homozygous form (β-thal major or β-thal intermedia):
 Hb Lepore is inadequately synthesized leading to an excess of α-chains and absence of HbA
and HbA2.
 hemosiderosis and chronic extravascular hemolysis.
 Hb Lepore ranges from 8–30%
Heterozygous (β-thal minor):
Asymptomatic, Hb Lepore concentration of 10%
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35. Combination Disorders
 HbS/β0-Type 1 (severe)
 HbS/β+ Type 1(moderate)
 HbS/β+ Type 2 (symptomatic)
 microcytic, hypochromic.
 target cells and the poikilocytes.
β:α ratio closer to 0.5
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36. Treatment
Regular blood transfusion:
 HbH disease (long-term thrapy, splenoctomy)
 β-Thal major (prolong life to 2ed or 3ed decade)
Moderate blood transfusion:
β-Thal intermedia (stress).
No need for blood transfusion:
α-Thal Minor, α-Trait, and βThal Minor.
-Regular transfusions minimize the stunting of growth and the
other consequences of chronic severe anemia.
- Iron chelation therapy with deferoxamine avoids iron overload
and the effects of iron toxicity. 23/02/1441
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37. [Pearson Clinical Laboratory Science Series] Shirlyn B. McKenzie
Ph.D. CLS (NCA), Lynne Williams - Clinical Laboratory Hematology
(3rd Edition)
(2014, Pearson)
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