You Make the Call
Each month in “You Make the Call,” we pick a challenging clinical question submitted through the Consult a Colleague program
and post the expert’s response, but we also want to know what you would do. Send in your response to next month’s clinical
dilemma and see how your answer matches up to the expert’s in the next print issue.
This month, Yvonne H. Datta, MD, discusses the treatment of gout in a patient with G6PD deficiency.
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 arthropathy, 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 percent, and a platelet count
of 438×10 9 /L. He is experiencing extreme pain and difficulty walking due to gouty arthropathy 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.
Expert Opinion
Yvonne H. Datta, MD
Professor of Medicine
Director, Hematology/Oncology Fellowship
Division of Hematology, Oncology, and Transplantation
University of Minnesota
Consult a Colleague
Through ASH
Consult a Colleague is a service for ASH
members that helps facilitate the exchange
of information between hematologists
and their peers. ASH members can
seek consultation on clinical cases from
qualified experts in 11 categories:
• Anemias
• Hematopoietic cell
transplantation
• Hemoglobinopathies
• Hemostasis/thrombosis
Pegloticase (Krystexxa), also known as pegylated rasbur-
icase, has been approved for use in severe refractory
gout. It is infused every two weeks and has a half-life
of 10 to 12 days. Rasburicase metabolizes uric acid
into allantoin, lowering serum uric acid levels with
decreased crystal formation. A byproduct of rasburicase
is hydrogen peroxide, which can cause oxidative stress.
G6PD is an enzyme in the pentose phosphate pathway
that converts glucose to pentose and also generates
NADPH, which protects against oxidative stress. G6PD
deficiency is an X-linked abnormality of varying sever-
ity that results in hemolysis when red cells are exposed
to significant oxidative stress. Patients such as this one,
with type III deficiency, have 10% to 60% of normal
G6PD activity. There have been several case reports of
significant hemolysis and methemoglobinemia when
rasburicase or pegloticase have been used in patients
with unrecognized G6PD deficiency, even when this
deficiency has been mild. In some cases, the hemolysis
was worsened when the patient was given methylene
blue for the methemoglobinemia, resulting in some
deaths. These reports have led to a boxed warning for
rasburicase and pegloticase, in which screening for
G6PD deficiency is recommended and use in patients
with known G6PD deficiency is discouraged.¹
In this patient, I advise against using pegloticase.
The use of rasburicase in the acute setting of newly
diagnosed high grade leukemia or lymphoma without
waiting for G6PD testing may be warranted. In that
event, G6PD testing is still advised in case additional
doses are needed later. However, in this case, the patient
is known to have G6PD deficiency. The use of peglot-
icase in this patient may cause serious harm. The con-
cern is not just that he may need transfusions. Severe
acute hemolysis can cause hyperkalemia, acute kidney
injury, and shock. This patient has chronic kidney
disease, placing him at greater risk for kidney injury.
One reported case of pegloticase-induced hemolysis
required transfusion, plasmapheresis, and vitamin C for
recovery.² Another reported case required prolonged
hemodialysis, possibly related to the long half-life of the
pegloticase causing ongoing hemolysis.³ In the setting
of G6PD deficiency, the potential harms of pegloticase
outweigh the potential benefits.
REFERENCES
• Leukemias
• Multiple myeloma & Waldenström
macroglobulinemia
• Myeloproliferative neoplasms
• Myelodysplastic syndromes
• Thrombocytopenias
Assigned volunteers (“colleagues”) will
respond to inquiries within two business
days (either by email or phone).
Have a puzzling clinical dilemma?
Submit a question, and read more
about Consult a Colleague volunteers at
hematology.org/Clinicians/Consult.aspx
or scan the QR code.
2. G eraldino-Pardilla L, Sung D, Xu JZ, et al. Methaemoglobinaemia and haemolysis following
pegloticase infusion for refractory gout in a patient with a falsely negative glucose-6-
phosphate dehydrogenase deficiency result. Rheumatology (Oxford). 2014;53:2310-1.
3. Minshar MA, Osman-Malik Y, Bhat ZY. Pegloticase-associated hemolysis. Am J Ther. 2018;
PMID: 30211701.
I have a 21-year-old female patient with Fanconi anemia (FA; compound heterozygous for FANCA) and bone marrow
failure, 46, triple X syndrome. She presented in October 2018 with moderate-severe cytopenias and was started on
granulocyte colony-stimulating factor (until November 2018) and eltrombopag. She does not have physical stigmata
of the diagnosis.
She responded to treatment reasonably well, but her response appears to be dwindling. We recently found two
matched unrelated donors (she has no matched siblings) and intend to take her for allogeneic hematopoietic cell
transplantation (alloHCT) as soon as possible. Could you advise me on the optimal timing for alloHCT, a stem cell
source (bone marrow vs. peripheral blood) and conditioning (Flu/Cy/ATG or Flu/Cy/ATG+TBI or other) for alloHCT? I
am not sure how triple X syndrome interacts with FA in terms of management and overall prognosis.
How would you respond? Email us at [email protected]. ●
ASH Clinical News
• Lymphoproliferative disorders
1. B elfield KD, Tichy EM. Review and drug therapy implications of glucose-6-phosphate
dehydrogenase deficiency. Am J Health Syst Pharm. 2018;75:97-104.
Next Month’s Clinical Dilemma:
40
• Lymphomas
* If you have a request related to a
hematologic disorder not listed here,
please email your recommendation to
[email protected] so it can be
considered for addition in the future.
DISCLAIMER: ASH does not recommend
or endorse any specific tests, physicians,
products, procedures, or opinions, and
disclaims any representation, warranty, or
guaranty as to the same. Reliance on any
information provided in this article is solely
at your own risk.
June 2019