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

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 sacrifice

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 hemoglobin-oxygen delivery to the tissues is increased

Table 101-4 Red Cell Enzyme Abnormalities Causing Hemolysis

(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)

y rare

CN

S, NM

May benefit from splenectomy

Pyruvate

kinase (PK)

e (2)

benefit from splenectomy

Red

ox

Glucose 6-phosphate

dehydrogenase

(G6PD)

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

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)

benefit from

(P5N) splenectomy

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