ASH Clinical News ACN_5.7_Digital | Page 15
You Make the Call: Readers’ Response
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Each month
G6PD deficienc
up to the expert’s
expert’s response
patient with
answer matches
and post the
of gout in a
treatment
see how your
discusses the
dilemma and
Datta, MD,
Yvonne H.
This month,
(World Health
(G6PD) deficiency to prolonged
cy secondary
e-dehydrogenase
rate is 27.
renal insufficien
r filtration
glucose-6-phosphat
y, and chronic
patient with
and his glomerula and a platelet count
ld male Samoan
s gouty arthropath
is 2.67 mg/dL
35.1 percent,
disabled
I have a 36-year-o III), chronic tophaceou His baseline creatinine hematocrit level of
y and has been
class
use.
g/dL,
to gouty arthropath
Organization
matory drug
level of 11.6
anti-inflam
hemoglobin difficulty walking due
known
nonsteroidal blood count of 13.8,
which is a
pain and
painful
ific enzyme,
ing extreme
He has a white
his extensive,
uric acid–spec
9
/L. He is experienc
e, a pegylated to try this agent to reduce
setting with
of 438×10
wants
e in a hospital
institute pegloticas
The patient
.
pegloticas
for eight years. logist would like to
ring
deficiency
His rheumato in patients with G6PD the possibility of administe
about
cause of hemolysis for other opinions
should occur.
looking
hemolysis
tophi. I am
brisk
support if
transfusion
ma:
Clinical Dilem
Colleague
Consult a
ASH
Through is a service for ASH
the exchange
Consult a Colleague
helps facilitate
gists
members that between hematolo
on
can
of informati
ASH members
from
and their peers. ion on clinical cases
seek consultat in 11 categories:
qualified experts
inion
Expert Op
• Anemias
oietic cell
• Hematop
transplantation
inopathies
• Hemoglob
osis
is/thromb
• Hemostas
Datta, MD
Yvonne H.
Medicine
Fellowship
Professor of
tation
/Oncology
ematology
and Transplan
Director, H
Oncology,
Hematology,
Division of
a
of Minnesot
University
setting of newly
in the acute
without
rasburicase
lymphoma
The use of
leukemia or
. In that
rasbur-
high grade
l
as pegylated
may be warranted
diagnosed
also known
G6PD testing advised in case additiona
(Krystexxa),
severe refractory
waiting for
the patient
for use in
Pegloticase
testing is still
half-life
in this case,
and has a
been approved
event, G6PD
later. However, The use of peglot-
icase, has
two weeks
es uric acid
infused every
doses are needed G6PD deficiency.
con-
se metaboliz
gout. It is
harm. The
with
to have
days. Rasburica
cause serious
uric acid levels
se is known
ns. Severe
of 10 to 12
patient may
transfusio
lowering serum byproduct of rasburica
icase in this
may need
. A
acute kidney
into allantoin,
stress.
just that he
hyperkalemia, kidney
crystal formation can cause oxidative
cern is not
can cause
decreased
pathway
peroxide, which
phosphate
acute hemolysis This patient has chronic
injury.
pentose
is hydrogen
kidney
the
shock.
risk for
also generates
enzyme in
injury, and
him at greater e-induced hemolysis
G6PD is an
pentose and
G6PD
glucose to
C for
disease, placing
oxidative stress.
that converts
case of pegloticas eresis, and vitamin
protects against ity of varying sever-
One reported
plasmaph
n,
prolonged
NADPH, which X-linked abnormal
are exposed
is an
required transfusio reported case required half-life of the
when red cells
one,
deficiency
Another
in hemolysis Patients such as this
to the long
recovery.²
ity that results
possibly related
stress.
.³ In the setting
normal
hemolysis
e
t oxidative
to 60% of
hemodialysis,
of
to significan
, have 10%
e causing ongoing
harms of pegloticas
case reports
III deficiency
pegloticas
, the potential
been several
with type
when
There have
globinemia
of G6PD deficiency
G6PD activity.
potential benefits.
and methemo used in patients
hemolysis
outweigh the
significant
e have been
this
phate
or pegloticas
, even when
of glucose-6-phos
deficiency
rasburicase
implications
REFERENCES
the hemolysis
ized G6PD
and drug therapy
In some cases, methylene
with unrecogn
Tichy EM. Review J Health Syst Pharm. 2018;75:97-104.
following
1. Belfield KD,
given
has been mild.
and haemolysis
deficiency. Am
was
naemia
deficiency
dehydrogenase
negative glucose-6-
when the patient ia, resulting in some
Xu JZ, et al. Methaemoglobi
with a falsely
lla L, Sung D,
for
was worsened
gout in a patient
(Oxford). 2014;53:2310-1.
2. Geraldino-Pardi
for refractory
Rheumatology
methemoglobinem to a boxed warning
pegloticase infusion
Am J Ther. 2018;
deficiency result.
led
blue for the
for
ociated hemolysis.
reports have
screening
phosphate dehydrogenase
These
Pegloticase-ass
which
ZY.
e, in
Y, Bhat
deaths.
Osman-Malik
and pegloticas nded and use in patients
3. Minshar MA,
rasburicase
is recomme
PMID: 30211701.
ed.¹
G6PD deficiency deficiency is discourag pegloticase.
G6PD
using
with known
I advise against
In this patient,
as
• Lymphom
disorders
roliferative
• Lymphop
s
• Leukemia
Waldenström
myeloma &
• Multiple
ulinemia
macroglob
s
liferative neoplasm
• Myelopro
s
plastic syndrome
• Myelodys
ytopenias
Thromboc
•
es”) will
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Assigned volunteer within two business
inquiries
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phone).
by email or
days (either
dilemma?
clinical
Have a puzzling
and read more s at
volunteer
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hematology.org/Cli
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* If you have
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ation to
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your recommend so it can be
.org
please email
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ashconsult@ addition in the future.
for
considered
marrow
and bone
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for FANCA)
started on
heterozygous
s and was
’s Clinical Dilemm
compound
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anemia (FA;
Next Month
with moderate
with Fanconi
does not
d
not recommen ,
: ASH does
tests, physicians
any specific
and
or endorse
, or opinions,
or
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tion, warranty,
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disclaims any
Reliance on
to the same.
is solely
guaranty as
in this article
n provided
informatio
risk.
at your own
DISCLAIMER
2018
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in October
ld female patient
and eltrombop
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I have a 21-year-o X syndrome. She presented November 2018)
. We recently
triple
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a stem cell
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optimal timing or other) for alloHCT?
matched siblings) advise me on the
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marrow vs.
interacts with [email protected].
source (bone
X syndrome
how triple
us at ashclinica
am not sure you respond? Email
How would
40
ASH Clinical
June 2019
News
We asked,
and you
answered!
Here are a few
responses
from this
month’s “You
Make the
Call.”
To see how the expert responded, turn to
page 40.
Clinical Dilemma:
I have a 36-year-old male Samoan
patient with glucose-6-phosphate-
dehydrogenase (G6PD) deficiency
(World Health Organization class III),
chronic tophaceous gouty arthropa-
thy, and chronic renal insufficiency
secondary to prolonged nonsteroidal
anti-inflammatory drug use. His
baseline creatinine is 2.67 mg/dL
and his glomerular filtration rate
is 27. He has a white blood count
of 13.8, hemoglobin level of 11.6 g/
dL, hematocrit level of 35.1%, and
a platelet count of 438×10 9 /L. He
is experiencing extreme pain and
difficulty walking due to gouty ar-
thropathy and has been disabled for
eight years.
His rheumatologist would like to
institute pegloticase, a pegylated
uric acid–specific enzyme, which
is a known cause of hemolysis in
patients with G6PD deficiency. The
patient wants to try this agent to
reduce his extensive, painful tophi. I
am looking for other opinions about
the possibility of administering
pegloticase in a hospital setting
with transfusion support if brisk
hemolysis should occur.
An initial erythrocytapheresis to
reduce G6PD-deficient red blood cells
and administration of pegloticase may
work. One can give the latter every
four weeks either with or without
erythrocytapheresis, depending on the
degree of subsequent hemolysis and
response to the drug.
Susumu Inoue, MD
Hurley Children’s Hospital
Flint, MI
Try pulse corticosteroid therapy at 50
mg once weekly. Taper with improve-
ment and treat side effects, such as
diabetes, if needed. Or try dexametha-
sone 20 mg once weekly. Treat side
effects, such as hyperglycemia, as
needed.
Herbert Goldman, MD
San Juan, Puerto Rico
I have considerable experience with
G6PD deficiency hemolysis, having been
part of the group led by Alf Alving, MD,
who discovered and characterized this
genetic disease. Since all known G6PD
mutations cause a loss of G6PD activity
as the red cells age, the youngest group
of cells in the circulation are resistant
to hemolysis. A good strategy for this
patient would be to start with a reduced
dose of the hemolytic drug, say 25%
of the known hemolytic dose, for two
weeks. During this time, mild hemolysis
would occur but reticulocytosis would
allow maintaining only a mild anemia.
Recovery to normal hemoglobin levels
would ensue, as this is a compensated
hemolytic anemia state. Then repeat
the process with a higher dose, say 50%
of the hemolytic dose, for another two
weeks. After the anemia is compensated,
increase to the full dose. It should be
George J. Brewer, MD
University of Michigan
Ann Arbor, MI
See more reader responses at ashclinicalnews.org/
you-make-the-call.
Know PK Deficiency
Would You Identify this
Underrecognized Cause
of Hemolytic Anemia?
Pyruvate kinase (PK) deficiency may
be underrecognized, 1 but should be
considered in patients with hemolysis
who lack evidence of an acquired
immune disorder. 1,2
Patients with PK deficiency may
experience:
• Chronic hemolytic anemia
• Iron overload even without transfusions
• Gallstones, splenomegaly, jaundice
Learn more about
ongoing clinical trials at
www.ActivateClinicalTrials.com
Diagnostic
Testing Program
New Testing Program*
Diagnostic testing is now available
from ARUP Laboratories —
at no cost to the patient.
Find out more online at
www.knowpkdeficiency.com/testing
* While Agios provides financial support for this program,
all tests and services are performed by the selected third-
party. Agios receives contact information for healthcare
professionals who submit tests under this program and
limited de-identified aggregate data.
1. Grace RF, et al. Am J Hematol. 2015;90(9):825-30. 2. Hirono A, et al. Chapter
182 Pyruvate Kinase Deficiency and Other Enzymopathies of the Erythrocyte.
New York, NY: McGraw Hill. 2014.
©2019 Agios Pharmaceuticals, Inc. All rights reserved. PKD-ALL-0051
ASHClinicalNews.org
possible to give the drug indefinitely,
recognizing that the patient is in a
chronic compensated hemolytic state.
Patient identification and
diagnosis are taking on new
importance.