MLAB 1415:Hematology Keri Brophy-Martinez

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MLAB 1415HematologyKeri Brophy-Martinez

• Chapter 10
• The Hemoglobinopathies
• Part Two

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Hemoglobin C Disease
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Introduction

• Amino acid substitution of lysine for glutamic
  acid at sixth position of Beta chain
• (a2ß26Glu-Lys)
• Is homozygous CC 
• Chronic hemolytic anemia with associated
  splenomegaly and abdominal discomfort

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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.

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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.

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Hemoglobin C Trait (AC)

• No symptoms no anemia. 
• Target cells frequent finding.

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Treatment for Hb C

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

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Hemoglobin SC Disease

• HbS gene is inherited from one parent and HbC
  gene is inherited from the other parent
• so both ß- chains are abnormal
• Splenomegaly
• Patients can develop vaso-occlusive crisis

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Peripheral Smear

• target cells
• folded red cells
• occasional glove-shaped intracellular crystals.

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Hemoglobin E Disease
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Hb E Disease

• ß chain variant lysine substituted for glutamic
  acid in 26th position in beta chain
• (a2ß226Glu-Lys)
• Heterozygous and homozygous forms.
• Frequently occurs with Beta thalassemia
• No clinical symptoms

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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

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Unstable Hemoglobin Variants
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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.

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Overview cont

• 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.

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Hemoglobin Variants with Altered Oxygen Affinity
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Methemoglobinemia (Hemoglobin M)
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Overview

• HbM contains ferric iron (Fe3) Cant carry
  oxygen and results in cyanosis.
• Three causes of methemoglobinemia
• Methemoglobin reductase system
• Overwhelmed
• Deficient
• Molecule is resistant to methemoglobin reductase

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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.

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Laboratory Findings in Hb M

• Blood is chocolate brown.
• Mild hemolytic anemia.
• Heinz bodies.
• M band on electrophoresis.

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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.

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Hemoglobins with Decreased Oxygen Affinity

• Increased release of oxygen to tissues.
• Patient may become anemic.

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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.