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, Josef Prchal, MD, discusses the significance of JAK2-positive test results in a healthy patient.
Clinical Dilemma:
Another clinician ordered a JAK2 test on a patient for unclear reasons. It was positive. The patient’s counts are normal,
and there are no thromboembolic events. What is the significance of this? Should anything be done?
Expert Opinion
Josef Prchal, MD
The Charles A. Nugent, M.D., and Margaret Nugent Endowed Professor
University of Utah & Huntsman Cancer Center
Our knowledge of clonal hematopoiesis of indeter-
minate potential (CHIP) is still evolving. However,
we are gaining more data due to the increasing
number of persons undergoing DNA evalu-
ation by whole genome sequencing. These
evaluations of their germline DNA have
also revealed the presence of acquired
somatic mutations, such as JAK2,
DNMTA3A and TET genes. These
mutations were previously thought to be
specific for and diagnostic of myeloid
malignancies, as they were originally
found in patients with morphological,
laboratory, and clinical evidence of
myeloid malignancies. However, more
recently, these mutations have been found
by chance in otherwise-healthy people
with normal laboratory and clinical findings;
indeed, this patient was one of these.
Our knowledge of this entity indicates that
some of the patients with JAK2 V617F or TET2 mutations
who have no clinical evidence of myeloproliferative neo-
plasm (MPN) on presentation never develop MPN, but
some of them do. These patients have an increased risk
of cardiovascular disease. Current evidence suggests that
there may be a common pathophysiology between car-
diovascular disease and MPN; indeed, both of them are
associated with augmentation of inflammation. Animal
studies also demonstrate that the presence or introduc-
tion of these CHIP somatic mutations also increases risk
of cardiovascular disease.
No immediate treatment is needed, but follow-up is
advised. Whether the CHIP mutations are also associated
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
• Lymphomas
• Lymphoproliferative disorders
• 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).
with an increased family prevalence of these mutations is
not clear. The MPNs characterized by JAK2, CALR, and
cMPL mutations are associated with increased risk of
MPNs in other family members. While these are acquired
mutations, there must be some yet-to-be defined family
predisposition to acquire these somatic mutations and
it remains to be established if that is also true for CHIP
mutations.
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.
Next Month’s Clinical Dilemma:
I have a 42-year-old female patient who has had very
low B 12 levels for at least a decade. This is the first
time she has seen a hematologist. She does not have
persistent anemia or red cell macrocytosis. She has no
neurologic symptoms. Her methylmalonic acid levels
and B 12 -binding capacity have been normal. She has had
a lot of gastrointestinal issues and, at various times,
small bowel Crohn disease as well as small intestine
bacterial overgrowth, which have required therapy.
At this time, she is not on any treatment other than
dietary restrictions and desipramine. Serology for
pernicious anemia and bowel biopsies looking for celiac
disease have been normal.
28
ASH Clinical News
In the past her B 12 level has increased moderately
when given supplementation, but she does not tolerate
parenteral, oral, or nasal supplementation so stopped
them. As far as she knows, there is no family history
of B 12 issues. My best guess is that she has some form
of B 12 -binding protein abnormality that is not of any
functional consequence. I tried to find a way to assay
for transcobalamin 1 but have not had success. Any
suggestions regarding further testing, if needed, or
management are welcomed.
How would you respond? Email us at
[email protected]. ●
* 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.
March 2019