Transcript The Hemoglobinopathies: Part Two

MLAB 1415:Hematology
Keri Brophy-Martinez
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)
◦ 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
Peripheral Smear

Numerous target cells, few
microspherocytes,
schistocytes, and folded
cells

May see hexagonal or rodshaped 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 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
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.
 Results in hemolytic anemia

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.
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
 Normal to decreased hemoglobin
concentration

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.