1. MLAB 1415:Hematology Keri Brophy-Martinez
The Hemoglobinopathies
Part Two

2. Hemoglobin C Disease

3. Introduction
Amino acid substitution of lysine for glutamic acid at sixth position of Beta chain
(α2β26Glu-Lys)
Is homozygous CC 
Chronic hemolytic anemia with associated splenomegaly and abdominal discomfort

4. Laboratory Findings: Hb C Disease
Mild to moderate anemia (8-12 g/dL)
Normochromic/normocytic
Retic count 4-8% (slightly increased)
Electrophoresis
Most hemoglobin is HbC
no HbA present
may or may not have increase in Hb F

5. Peripheral Smear
Numerous target cells, few microspherocytes, schistocytes, and folded cells
May see hexagonal or rod- shaped crystals
"bar of gold” 
Usually intracellular. Are elongated with blunt ends and parallel sides.

6. Hemoglobin C Trait (AC)
No symptoms – no anemia.
Target cells frequent finding

7. Treatment for Hb C
Splenectomy may be beneficial for symptomatic CC homozygous persons.
AC heterozygous persons are usually asymptomatic, so no treatment required.

8. Hemoglobin E Disease

9. Hb E Disease
β chain variant – lysine substituted for glutamic acid in 26th position in beta chain
(α2β226Glu-Lys)
Heterozygous and homozygous forms
Frequently occurs with Beta thalassemia
No clinical symptoms

10. Laboratory Findings: Hb E Disease
Mild, microcytic, hypochromic hemolytic anemia
Many target cells
Electrophoresis shows E band. Normal Hb F, no Hb A
May protect against malaria

11. Unstable Hemoglobin Variants

12. Overview
Unstable hemoglobins are hemoglobin variants in which amino acid substitutions or deletions have weakened the binding forces that maintain the structure of the molecule.
Instability may cause Hb to denature and precipitate in the red cells as Heinz bodies.
Results in hemolytic anemia

13. Unstable Hemoglobin Disorders
Most inherited as autosomal dominant disorders.
When anemia is present, degree of hemolysis varies considerably:
Most have mild compensated anemia with mild reticulocytosis
Some have severe, chronic hemolysis with splenomegaly and jaundice.
Hb electrophoresis usually not very helpful in diagnosis.

14. Hemoglobin Variants with Altered Oxygen Affinity

15. Methemoglobinemia (Hemoglobin M)

16. Overview
HbM contains ferric iron (Fe3+); Can’t carry oxygen and results in cyanosis.
Three causes of methemoglobinemia:
Methemoglobin reductase system
Overwhelmed
Deficient
Molecule is resistant to methemoglobin reductase

17. Hb M
5 variants of Hb M which result from single amino acid substitution in the globin chain that stabilizes iron in the ferric form.
Patients have cyanosis, but are otherwise asymptomatic and no treatment is given.

18. Laboratory Findings in Hb M
Blood is chocolate brown.
Mild hemolytic anemia.
Heinz bodies.
M band on electrophoresis.

19. Hemoglobins with Increased Oxygen Affinity
Decreased delivery of oxygen to tissues
Hb values from normal to 20 g/dL
Leukocytes and platelets normal
Normal life span
No treatment
Often results in polycythemia

20. Hemoglobins with Decreased Oxygen Affinity
Increased release of oxygen to tissues
Normal to decreased hemoglobin concentration

21. Referenes
Harmening, D. M. (2009). Clinical Hematology and Fundamentals of hemostasis (5th ed.). Philadelphia, PA: F.A. Davis Company.
McKenzie, S. B. (2010). Clinical Laboratory Hematology (2nd ed.). Upper Saddle River, NJ: Pearson Education, Inc.
Rodak, B. F. (2002). Hematology Clinical Principles and Applications (3rd ed.). St. Louis: Saunders Elsevier.