MLAB 1415-Hematology Keri Brophy-Martinez

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MLAB 1415-HematologyKeri Brophy-Martinez

• Chapter 16 Hemolytic Anemias Enzyme Deficiencies

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Introduction

• Enzyme deficiency within the rbc leads to
  hemolytic anemia
• Deficiencies compromise the integrity of the cell
  membrane or hgb causing hemolysis
• Most common are those associated with hexose
  monophosphate shunt and glycolytic pathway

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Review of RBC Metabolism

• Enzymes within the rbc are limited
• Enzymes that protect the cell from oxidant damage
  and provide the cell with energy are essential
  for cell survival
• Mature rbcs depend entirely on anaerobic glucose
  metabolism for energy needs

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Clinical Findings

• Normocytic, normochromic anemia
• Reticulocytosis
• Hyperbilirubinemia
• Neonatal jaundice

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HEREDITARY ENZYME DEFICIENCIES

• Glucose-6-Phosphate Dehydrogenase Deficiency
  (G6PD)
• Sex-linked(X) disorder
• Affects Africans, Chinese, and Mediterraneans
• Most common enzyme disorder
• Denatured hemoglobin precipitates in the RBC
  after exposure to oxidative stress causing
  hemolysis

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HMP Shunt Normal Function

• GSH levels maintained by NADPH to NADP
• NADP is reduced back to NADPH by G6PD

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HMP Shunt Deficient

• Oxidizing agent causes increase of NADPH
• System is overwhelmed
• Oxidized hgb accumulates as Heinz bodies

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Causes of oxidative stress

• Ingestion of oxidative drugs
• Antimalaria drugs (i.e Primaquine)
• Quinine, quinidine
• Analgesics
• Ingestion of fava beans
• Favism is found in the Mediterranean area
• Person eats or inhales fava bean or its pollen
• Hereditary

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Laboratory features G6PD deficiency

• Decreased HH (hemoglobin and hematocrit)
• Hemoglobinuria
• Increased bilirubin and LD
• Reticulocytosis

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Morphology

• Blister cell

• Bite cell

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HEREDITARY ENZYME DEFICIENCIES

• Pyruvate kinase deficiency (PK)
• Autosomal recessive anemia
• Red cells are unable to retain water which
  results in hemolysis, due to cell shrinkage,
  distortion of shape and increased membrane
  rigidity
• Pyruvate kinase is an essential enzyme in the
  Glycolytic/Embden-Meyerhof pathway

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Glycolytic Pathway Normal

• PK converts PEP to pyruvate, with the conversion
  of ADP to ATP

PEP
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Glycolytic Pathway Deficient

• Energy can not be produced, due to lack of ATP
• Results in alteration of rbc membrane,
  dehydration, pump malfunction

PEP
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Clinical Findings

• Symptoms vary depending on the degree of the
  anemia
• Jaundice
• Gallstones

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Laboratory features of PK

• HH - slight? to marked ?
• P.S
• severity of anemia dictates degree of
  reticulocytosis, polychromasia, aniso, poik and
  NRBCs.
• Definitive test is PK enzyme assay.
• Fluorescent screening test

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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.
• http//botany.csdl.tamu.edu/FLORA/cgi/gallery_quer
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