Download MLAB 1315-Hematology Fall 2007 Keri Brophy

MLAB 1415-Hematology
Keri Brophy-Martinez
Chapter 16: Hemolytic Anemias:
Enzyme Deficiencies
Introduction
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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
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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
Clinical Findings
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Normocytic, normochromic anemia
Reticulocytosis
Hyperbilirubinemia
Neonatal jaundice
HEREDITARY ENZYME
DEFICIENCIES
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Glucose-6-Phosphate Dehydrogenase Deficiency
(G6PD)
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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
HMP Shunt: Normal Function

GSH levels
maintained by
NADPH to NADP

NADP is reduced
back to NADPH
by G6PD
HMP Shunt: Deficient

Oxidizing agent causes
increase of NADPH

System is overwhelmed

Oxidized hgb
accumulates as Heinz
bodies
Causes of oxidative stress

Ingestion of oxidative drugs

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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
HEREDITARY ENZYME
DEFICIENCIES

Pyruvate kinase deficiency (PK)
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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

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Symptoms vary depending on the degree of
the anemia
Jaundice
Gallstones
Laboratory features of PK
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H&H - slight↓ to marked ↓
P.S
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severity of anemia dictates
degree of reticulocytosis,
polychromasia, aniso, poik
and NRBC’s.
Definitive test is PK
enzyme assay.
 Fluorescent screening
test
Referenes
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
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