MLAB 1415-Hematology Keri Brophy-Martinez

1. MLAB 1415-HematologyKeri Brophy-Martinez 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. Laboratory & 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, Middle East, Americas, 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 the conversion of NADPH to NADP • NADP is reduced back to NADPH by G6PD Oxidant H2O2 H20

7. HMP Shunt: Deficient • Oxidative stress triggers response • Unable to generate NADPH to reduce GSH • System is overwhelmed • Oxidized hgb accumulates as Heinz bodies Oxidant H2O2 H20

8. Causes of oxidative stress • Infections • Mechanism not clear • Release of hydrogen peroxide from the WBCs • 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 Not a Heinz Body Heinz Bodies

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 theGlycolytic/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 ↓ • Reticulocytosis • P.S • severity of anemia dictates degree of, 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. • http://botany.csdl.tamu.edu/FLORA/cgi/gallery_query?q=Vicia+faba+faba+faba