MLAB 1415:HematologyMLAB 1415:HematologyKeri Brophy-MartinezKeri Brophy-Martinez

Chapter 10:The HemoglobinopathiesPart Two

Hemoglobin C Hemoglobin C DiseaseDisease

IntroductionIntroductionAmino acid substitution of lysine for

glutamic acid at sixth position of Beta chain◦ (α2β2

6Glu-Lys)Is homozygous CC 

Chronic hemolytic anemia with associated splenomegaly and abdominal discomfort

Laboratory Findings:Laboratory Findings: Hb C Disease 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 SmearPeripheral SmearNumerous 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)Hemoglobin C Trait (AC)

No symptoms – no anemia.  Target cells frequent finding.

Treatment for Hb CTreatment 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 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

SplenomegalyPatients can develop vaso-occlusive

crisis

Peripheral SmearPeripheral Smeartarget cellsfolded red cells occasional

glove-shaped intracellular crystals.

Hemoglobin E Hemoglobin E DiseaseDisease

Hb E DiseaseHb E Diseaseβ chain variant – lysine substituted for

glutamic acid in 26th position in beta chain◦ (α2β2

26Glu-Lys) Heterozygous and homozygous

forms. Frequently occurs with Beta

thalassemia No clinical symptoms

Laboratory Findings:Laboratory Findings: Hb E Disease 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 Unstable Hemoglobin Hemoglobin VariantsVariants

OverviewOverviewUnstable 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’tOverview 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 Hemoglobin Variants with Variants with Altered Oxygen Altered Oxygen AffinityAffinity

Methemoglobinemia Methemoglobinemia (Hemoglobin M)(Hemoglobin M)

OverviewOverview

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 MHb 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 Laboratory Findings in Hb MM

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

electrophoresis.

Hemoglobins with Increased Hemoglobins with Increased Oxygen AffinityOxygen 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 Hemoglobins with Decreased Oxygen AffinityOxygen Affinity

Increased release of oxygen to tissues.

Patient may become anemic.

ReferenesReferenesHarmening, 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.