Chapter 101. Hemolytic Anemias and Anemia Due to Acute Blood Loss (Part 8) pdf

Chapter 101. Hemolytic Anemias and Anemia
Due to Acute Blood Loss
(Part 8)

Abnormalities of the Glycolytic Pathway
(Fig. 101-1) Since red cells, in the course of their differentiation, have
sacrificed not only their nucleus and their ribosomes but also their mitochondria,
they rely exclusively on the anaerobic portion of the glycolytic pathway for
producing energy in the form of ATP. Most of the ATP is required by the red cell
for cation transport against a concentration gradient across the membrane. If this
fails, due to a defect of any of the enzymes of the glycolytic pathway, the result
will be hemolytic disease.
Pyruvate Kinase Deficiency
Abnormalities of the glycolytic pathway are all inherited and all rare (Table
101-4). Among them, deficiency of pyruvate kinase (PK) is the least rare, with an
estimated prevalence of 1:10,000. The clinical picture is that of an HA that often
presents in the newborn with neonatal jaundice; the jaundice persists and is usually
associated with a very high reticulocytosis. The anemia is of variable severity;
sometimes it is so severe as to require regular blood transfusions; sometimes it is
mild, bordering on a nearly compensated hemolytic disorder. As a result, the
diagnosis may be delayed, and in some cases it is made in young adults—for
instance, in a woman during her first pregnancy, when the anemia may get worse.
In part the delay in diagnosis is due to the fact that the anemia is remarkably well-
tolerated because the metabolic block at the last step in glycolysis causes an
increase in bisphosphoglycerate (or DPG), a major effector of the hemoglobin-
oxygen dissociation curve. Thus, the oxygen delivery to the tissues is increased.
Table 101-4 Red Cell Enzyme Abnormalities Causing Hemolysis

Enzyme
(Acronym)
Chro

mosomal
Location
Pre
valence of
Enzyme
Deficiency
(Rank)
Cli
nical
Manifest
ations
Extra-
Red Cell
Commen
ts
Gly Hexokina 10q22

Ver Other
colytic
pathway
se (HK) y rare isoenzymes
known.
Glucose
6-phosphate
isomerase
(G6PI)
19q31
.1
Rar
e (4)

N
M, CNS

Phosphof
ructokinase
(PFK)
12q13

Ver
y rare
My
opathy

Aldolase

16q22
-24
Ver
y rare

Triose
phosphate
isomerase (TPI)

12p13

Ver
y rare
CN
S

(severe),
NM

Glycerald 12p13 Ver My
ehyde 3-
phosphate
dehydrogenase
(GAPD)
.31–p13.1 y rare opathy
Diphosph
oglycerate
mutase (DPGM)

7q31-
q34
Ver
y rare
Erythrocy
tosis rather than
hemolysis.
Phosphog
lycerate kinase
(PGK)
Xq13 Ver
y rare
CN
S, NM
May
benefit from
splenectomy.

Pyruvate
kinase (PK)
1q21 Rar
e (2)
May
benefit from
splenectomy.
Red
ox
Glucose
6-phosphate
dehydrogenase
(G6PD)
Xq28 Co
mmon (1)
Ve
ry rarely
granulocy
tes
In almost
all cases only
AHA from
exogenous
trigger.
Glutathio
ne synthase
20q11
.2
Ver
y rare

CN
S

γ-
Glutamylcystein
e synthase
6p12 Ver
y rare
CN
S

Cytochro
me b5 reductase

22q13
.31–qter
Rar
e
CN
S
Methemo
globinemia
rather than
hemolysis.
Nu
cleotide
metabolis
m
Adenylate
kinase (AK)

9q34.
1
Ver
y rare
CN
S

Pyrimidin
e 5'-
nucleotidase
3q11–
q12
Rar
e (3)
May
benefit from
(P5N) splenectomy.

Note: CNS, central nervous system; AHA, acquired hemolytic anemia.