Transcript The Hemoglobinopathies: Part Two

MLAB 1415:Hematology
Keri Brophy-Martinez
Chapter 10:
The Hemoglobinopathies
Part Two
Hemoglobin C Disease
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
Laboratory Findings:
Hb C Disease

Mild to moderate anemia (8-12 g/dL)

Retic count 4-8% (slightly increased)

Electrophoresis
◦ Most hemoglobin is HbC
◦ no HbA present
◦ may or may not have increase in Hb F.
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.
Hemoglobin C Trait (AC)
No symptoms – no anemia.
 Target cells frequent finding.

Treatment for Hb C

Splenectomy may be beneficial for
symptomatic CC homozygous persons.

AC heterozygous persons are usually
asymptomatic, so no treatment required.
Hemoglobin SC Disease

HbS gene is inherited from one parent and HbC
gene is inherited from the other parent
◦ so both β- chains are abnormal
Splenomegaly
 Patients can develop vaso-occlusive crisis

Peripheral Smear
target cells
 folded red cells
 occasional gloveshaped intracellular
crystals.

Hemoglobin E
Disease
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

Laboratory Findings:
Hb E Disease
Similar to Hb D
 Mild, microcytic, hypochromic hemolytic
anemia
 Many target cells
 Electrophoresis shows E band. Normal
Hb F, no Hb A
 May protect against malaria

Unstable
Hemoglobin Variants
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.
Overview con’t
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.
Hemoglobin Variants
with Altered Oxygen
Affinity
Methemoglobinemia
(Hemoglobin M)
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
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.

Laboratory Findings in Hb M
Blood is chocolate brown.
 Mild hemolytic anemia.
 Heinz bodies.
 M band on electrophoresis.

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.

Hemoglobins with Decreased Oxygen
Affinity
Increased release of oxygen to tissues.
 Patient may become anemic.

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.