ASH Clinical News September 2015 | Page 72
PAID ADVERTISEMENT
Polycythemia Vera:
Are Some Patients at Increased Risk?
For some patients whose hematocrit levels remain elevated, and for those who continue to experience clinical signs and
symptoms such as fatigue, pruritus, night sweats or splenomegaly, PV remains uncontrolled.
Overview
Thrombotic and hemorrhagic complications are among the leading
causes of morbidity and mortality associated with PV.14 Cancer and
What Is Polycythemia Vera?
Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) cardiovascular mortality are the frequent causes of deaths in PV.6,15
characterized by an overproduction of
When assessing risks for morbidity
normal red blood cells, white blood cells
and mortality in patients, consider
and platelets that leads to an increased risk
the following3,14,16:
The
rate
of
death
of thrombosis.1-4 Erythrocytosis (elevated
• Elevated hematocrit levels
due
to
cardiovascular
• History of thrombosis
red blood cell mass) is the most prominent
clinical manifestation of PV, distinguishing it
events or major thrombosis • Advanced age (≥60 years)
5
• Leukocytosis
from other MPNs.
was four times higher
• Cardiovascular risk factors
such as high cholesterol levels,
PV may occur at any age but often presents
in
patients
with
elevated
hypertension, diabetes, obesity
later in life, with a median age at diagnosis of
6,7
and smoking
60 years. Approximately 100,000 patients
hematocrit levels of 45%
8
in the United States are living with PV.
to 50% compared with
According to data from a large,
randomized, controlled clinical trial,
Clinical Presentation of PV
those who maintained
the rate of death due to cardiovascular
Contributing to Its Diagnosis
a hematocrit target
events or major thrombosis was
Janus kinases (JAKs) mediate cytokine
9,1 0
four times higher in patients with
signaling and growth factors.
An
2
of
<45%.
elevated hematocrit levels of 45%
important genetic discovery about a point
to 50% compared with those who
mutation in the Janus kinase 2 (JAK2) gene
11
maintained a hematocrit target of
has enhanced the understanding of PV.
<45%2 (Figure 1).
The specific JAK2V617F mutation is detected in >95% of
patients with PV.5 Although the JAK2V617F mutation is the key
driver of PV, an understanding of the clinical presentation of PV
will help to facilitate a more accurate diagnosis.
PV
PV is an elusive disease that may not be recognized for years.
Diagnosis most frequently occurs by chance following a routine
examination.12 Diagnosis may also occur after a thrombotic event
or as a result of disease-related symptoms.12
The following important signs and symptoms warrant a prompt
evaluation and suggest PV 6,7:
• Elevated hemoglobin or hematocrit levels
• Thrombotic events
• Splenomegaly (with or without thrombocytosis and/or
leukocytosis)
Clinical Considerations
in Managing PV
Prognosis and Risk Factors
In a large population-based study in more than 4,000 patients
with PV, life expectancy was 36% lower than that of the general
population.13
CI = confidence interval; Hct = hematocrit.
Figure 1. Kaplan-Meier curve for total cardiovascular events.
From The New England Journal of Medicine. Marchioli R, Finazzi, G, Specchia G, et al. Cardiovascular
events and intensity of treatment in polycythemia vera. N Engl J Med. 2013;368(1):22-33. Copyright ©2013
Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.
Thrombosis, Splenomegaly and Other Diseaserelated Symptoms
In PV, a wide spectrum of thrombotic manifestations exists that
may occur before the disease is diagnosed.14 Palpable splenomegaly
is an important physical finding because increased spleen size is
present in 30% to 40% of patients with PV.12 Additional signs and
symptoms of PV, which may contribute to a substantial quality-oflife burden in patients with PV, include17:
• Fatigue
• Pruritus
• Night sweats