MLAB 1415-Hematology

Keri Brophy-Martinez

Hemolytic Anemias: Enzyme Deficiencies

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

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

Laboratory & Clinical Findings

Normocytic, normochromic anemia Reticulocytosis Hyperbilirubinemia/ Neonatal jaundice

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

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

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

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

Laboratory features: G6PD deficiency

Decreased H&H (hemoglobin and hematocrit) Hemoglobinuria Increased bilirubin and LD Reticulocytosis

Morphology

Blister cell Bite cell

Heinz BodiesNot a Heinz Body

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

Glycolytic Pathway: Normal

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

PEP

Glycolytic Pathway: Deficient

Energy can not be produced, due to lack of ATP

Results in alteration of rbc membrane, dehydration, pump malfunction

PEP

Clinical Findings

Symptoms vary depending on the degree of the anemia

Jaundice Gallstones

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

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