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 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 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.