1. MLAB 1415-Hematology Keri 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 H 2 O 2 H 2 0

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 H 2 O 2 H 2 0

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 cellBite cell Heinz Bodies Not a Heinz Body

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 ↓ 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/galler y_query?q=Vicia+faba+faba+faba