1. MLAB 1415-Hematology Keri Brophy-Martinez
Chapter 16: Hemolytic Anemias: Enzyme Deficiencies

2. 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

3. 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

4. Clinical Findings Normocytic, normochromic anemia Reticulocytosis
Hyperbilirubinemia
Neonatal jaundice

5. 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

6. HMP Shunt: Normal Function
GSH levels maintained by NADPH to NADP
NADP is reduced back to NADPH by G6PD

7. HMP Shunt: Deficient Oxidizing agent causes increase of NADPH
System is overwhelmed
Oxidized hgb accumulates as Heinz bodies .

8. 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

9. Laboratory features: G6PD deficiency
Decreased H&H (hemoglobin and hematocrit)
Hemoglobinuria
Increased bilirubin and LD
Reticulocytosis

10. Morphology
Blister cell
Bite cell

11. 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

12. Glycolytic Pathway: Normal
PK converts PEP to pyruvate, with the conversion of ADP to ATP
PEP

13. Glycolytic Pathway: Deficient
Energy can not be produced, due to lack of ATP
Results in alteration of rbc membrane, dehydration, pump malfunction
PEP

14. Clinical Findings Symptoms vary depending on the degree of the anemia
Jaundice
Gallstones

15. Laboratory features of PK
H&H - slight↓ to marked ↓
P.S
severity of anemia dictates degree of reticulocytosis, polychromasia, aniso, poik and NRBC’s.
Definitive test is PK enzyme assay.
Fluorescent screening test

16. 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.