1. MLAB 1415: Hematology Keri Brophy-Martinez
Thalassemia:
Part One

2. Overview
Diverse group of congenital disorders which manifest as anemia of varying degrees.
Can be either homozygous or heterozygous inheritance
Result of quantitative defective production of one or more globin portion(s) of hemoglobin molecule.
The decreased globin production causes
Imbalanced globin chain synthesis
Defective hemoglobin production
Damage to the RBC

3. Thalassemia Distribution

4. Thalassemia
Results in overall decrease in amount of hemoglobin produced and may induce hemolysis.
Two major types of thalassemia:
Alpha (α) - Caused by defect in rate of synthesis of alpha chains.
Beta (β) - Caused by defect in rate of synthesis in beta chains.
May contribute protection against malaria.

5. Review of Hgb Structure
Normal globin genes
Alpha, beta, delta, gamma
Form hgb A (97%), hgb A2(2-3%), hgb F (2%)
Epsilon, zeta: in utero
Gamma: 3rd trimester until birth
Adult hemoglobin composed two alpha and two beta chains
Thalassemia causes an excess or absence of one of these chains

6. Pathophysiology: Beta Thalassemia
α-chain excess
unstable
Precipitates within the cell, causes damage
Macrophages destroy the damaged RBCs in the bone marrow, leads to ineffective erythropoiesis
Spleen also removes damaged RBCs, leads to chronic extravascular hemolysis

7. Pathophysiology: Alpha Thalassemia
β-chain excess
Unstable
Combines to form hgb molecules with 4 β- chains (Hemoglobin H)
Infants: excess gamma chains combine with hgb molecules (Hemoglobin Bart’s)
High oxygen affinity, poor transporter of oxygen

8. Clinical and Laboratory Findings Associated with Thalassemia

9. Clinical Findings

10. Comparison of Hemoglobinopathies and Thalassemias
Disease
RBC count
Indices
RBC Morph
Abnormal Hb
Ancestry
Retic Count
Hemoglobinopathy
Normocytic
Normochromic
Target cells, sickle cells (HbS),
Crystals (HbC)
HbS,HbC, HbE etc
African
Mediterranean
Middle Eastern
Asian
Thalassemia
Microcytic
Hypochromic
Target cells, basophilic stippling
HbH
Hb Bart’s
Thalassemia: globin chains structurally normal
Hemoglobinopathies: globin chain is abnormal

11. Beta Thalassemia

12. Classical Syndromes of Beta Thalassemia
Beta thalassemia minima/ Silent carrier state – the mildest form of beta thalassemia.
Beta thalassemia minor - heterozygous disorder resulting in mild hypochromic, microcytic hemolytic anemia.
Beta thalassemia intermedia - Severity lies between the minor and major.
Beta thalassemia major - homozygous disorder resulting in severe transfusion- dependent hemolytic anemia.

13. Beta Thalassemia Minor
Caused by heterogenous mutations that affect beta globin synthesis. 
Usually presents as mild, asymptomatic hemolytic anemia 
Have one normal beta gene and one mutated beta gene.

14. Beta Thalassemia Minor
Anemia usually mild
Rarely see hepatomegaly or splenomegaly.
Have high Hb A2 levels %
Normal to slightly elevated Hb F levels.
Different variations of this form depending upon which gene has mutated
Normally require no treatment.
Iron deficiency anemia. Should be ruled out

15. Beta Thalassemia Major/ Cooley’s anemia
Severe microcytic, hypochromic anemia. 
Severe anemia causes marked bone changes due to expansion of marrow space for increased erythropoiesis.
See characteristic changes in skull, long bones, and hand bones “hair on end”
Detected early in childhood- 6 months- 2 yrs.
Hb A production is reduced
HbA2 and Hg F production increased

16. Clinical Findings: β-Thalassemia Major
Infants
Irritability, pallor, failure to thrive
Diarrhea, fever, enlarged abdomen
Severe anemia
Cardiac failure
Bronze pigmentation of skin
Bone changes
Bossing of skull, facial deformities, “hair-on-end” appearance of skull
Hepatosplenomegaly

17. Laboratory Findings: β-Thalassemia Major
Hb can be as low as 2–3 g/dL
Microcytic hypochromic
MCV < 67 fL, ↓ MCH and MCHC
Peripheral blood smear
Anisocytosis and poikilocytosis
Basophilic stippling, polychromasia
NRBCs
↑ RDW

18. β-Thalassemia Major Treatment Prognosis Regular transfusions
Minimize anemia
Suppress ineffective erythropoiesis
Iron-chelating agents
Reduce excess iron absorption
Splenectomy
Prognosis
Untreated – die during 1st or 2nd decade
Hypertransfusion with iron chelation
Extend for ≥ 1 decade

19. Hereditary Persistence of Fetal Hemoglobin (HPFH)
Rare condition characterized by  continued synthesis of Hemoglobin F in adult life. 
Do not have usual clinical symptoms of thalassemia.
Kleihauer-Betke stain useful tool to identify

20. References
Harmening, D. M. (2009). Clinical Hematology and Fundamentals of Hemostasis. Philadelphia: F.A Davis.
McKenzie, S. B., & Williams, J. L. (2010). Clinical Laboratory Hematology. Upper Saddle River: Pearson Education, Inc.