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Introduction
Polycythemia vera is a chronic
myeloproliferative disorder characterized
by increased red blood cell mass (RCM),
or erythrocytosis
The resultant hyperviscosity of the blood
predisposes such patients to thrombosis
Introduction
Increased RCM is accompanied by
increased white blood cell (myeloid) and
platelet (megakaryocytic) production,
which is due to an abnormal clone of the
hematopoietic stem cells with increased
sensitivity to the different growth factors
for maturation.
Introduction
Its etiology is not fully established, but
hypersensitivity to interleukin-3 may play a
role in the sustained erythrocytosis
observed in this disease.
Introduction
Polycythemia vera should be suspected in
patients with elevated hemoglobin or
hematocrit levels, splenomegaly, or portal
venous thrombosis.
Introduction
Secondary causes of increased red blood
cell mass (e.g., heavy smoking, chronic
pulmonary disease, renal disease) are
more common than polycythemia vera and
must be excluded
Introduction
Patients may present with complaints of pruritus
after bathing, burning pains in the distal
extremities (erythromelalgia), gastrointestinal
disturbances, or nonspecific complaints such as
weakness, headaches, or dizziness.
Other patients are diagnosed after an incidental
finding of an elevated hemoglobin and/or
hematocrit level on a complete blood count.
Introduction
Diagnosis is made using criteria
developed by the Polycythemia Vera
Study Group; major criteria include
elevated red blood cell mass, normal
oxygen saturation, and palpable
splenomegaly.
Introduction
Untreated patients may survive for six to
18 months, whereas adequate treatment
may extend life expectancy to more than
10 years.
Introduction
Treatment includes phlebotomy with the
possible addition of myelosuppressive
agents based on a risk-stratified approach.
Agents under investigation include
interferon alfa-2b, anagrelide, and aspirin.
Consultation with a hematologist is
recommended.
Introduction
Alternative Names:
Primary polycythemia
Polycythemia rubra vera
Myeloproliferative disorder
Erythremia
Splenomegalic polycythemia
Vaquez's disease
Osler's disease
Polycythemia with chronic cyanosis
Myelopathic polycythemia
Erythrocytosis megalosplenica
Cryptogenic polycythemia
Pathophysiology
Normal stem cells are present in the bone
marrow of patients with PV.
Also present are abnormal clonal stem
cells that interfere with or suppress normal
stem cell growth and maturation.
Pathophysiology
Evidence indicates that the etiology of
panmyelosis is unregulated neoplastic
proliferation.
The origin of the stem cell transformation
remains unknown
Polycythemia vera
Bone marrow film at 100X magnification
demonstrating hypercellularity and
increased number of megakaryocytes
Pathophysiology
Thromboses and bleeding are frequent in
persons with PV and myeloproliferative
disease (MPD), and they result from the
disruption of hemostatic mechanisms
because of
an increased level of red blood cells
an elevation of the platelet count
Pathophysiology
Tissue factor is also synthesized by blood
leukocytes, the level of which is increased
in persons with MPD, which can contribute
to thrombosis.
Pathophysiology
Hyperhomocystinemia is a risk factor for
thrombosis and is also widely prevalent in
patients with MPD (35% in controls, 56%
in persons with PV).
Statistics
Polycythemia vera is a rare disease
The peak incidence of PV is age 50-70
years
However, it occurs in persons of all age
groups, including those in early adulthood and
childhood, albeit rarely.
The disease is slightly more common in
males than in females.
History
The disease usually develops slowly
Symptoms are often insidious in onset
Major Criteria
total RBC vol
Men > or = to 36 mL/kg
Women > or = to 32 mL/kg
arterial 02 saturation > or = to 92%
Splenomegaly
Minor Criteria
Thrombocytosis with platelet count > 400,000/mL
Leukocytosis with WBC > 12,000/mL
Increased leukocyte alkaline phosphatase LAP > 100U/L (no infection)
Serum B12 > 900 pg/mL or binding capacity UB12 BC > 2200 pg/mL
Serum Epo assay
Epo levels in patients with PV are often
below the lower limit of normal compared
with patients with secondary erythrocytosis
and pseudoerythrocytosis
but the levels for PV and secondary
erythrocytosis or pseudoerythrocytosis
overlap and are nonspecific for differentiating
these conditions.
Bone marrow morphology and
histology
Overall hypercellularity with expansion of all cell
lines with megakaryocytic proliferation and the
presence of myelofibrosis can help diagnose PV
and MPD
PV patients may have normal bone marrow
findings
These results are nonspecific and may be
observed in the other Philadelphia
chromosome–negative MPDs.
Bone marrow findings for
Polycythemia vera include
Moderate to marked hypercellularity
trilineage hyperplasia
megakaryocytes increased;
hyperlobulated
dilated sinusoids with intravascular
hematopoiesis
decreased or absent iron stores
increased reticulin (only in a minority of
patients)
Labs
Peripheral blood findings
Increased hemoglobin & hematocrit
Normal red blood cell morphology, unless iron
deficient or spent phase
Normoblasts may be present
Mild to moderate leukocytosis
Mild neutrophilia and/or basophilia
Thrombocytosis
Labs
This disease may also alter the results of the
following tests:
Lactate dehydrogenase
u/a
Serum uric acid
T- wbc
RBC count
Platelet aggregation test
Leukocyte alkaline phosphatase
Hemoglobin
ESR
Erythropoietin
Labs
Automated red blood cell counts and hematocrit values
(including hemoglobin levels) may be deceptive with
regard to the total red blood cell mass.
Direct measurement of the red blood cell mass should
show an increase with a normal or slightly decreased
plasma volume.
This is a nuclear medicine test that uses radiochromium-labeled
red blood cells to measure actual red blood cell and plasma
volume.
However, patients with hemoglobin concentrations of at
least 20 g/dL or hematocrit values of at least 60% in
males and 56% in females always have an elevated red
blood cell mass.
Labs
The red blood cells in patients with PV are
usually normochromic normocytic unless
the patient has been bleeding from
underlying peptic ulcer disease or
phlebotomy treatment (wherein the cells
may be hypochromic and microcytic,
reflecting low iron stores).
Labs
An elevated white blood cell count (>12,000/µL)
occurs in approximately 60% of patients. It is
mainly composed of neutrophils with a left shift
and a few immature cells.
Mild basophilia occurs in 60% of patients.
The leukocyte alkaline phosphatase score is elevated
(>100 U/L) in 70% of patients.
This technique is only semiquantitative and is
susceptible to laboratory errors unless it can be
performed by flow cytometry, which is not routinely
available
Labs
The platelet count is elevated to 400,000-
800,000/mL in approximately 50% of
patients.
Labs
The release of potassium into the serum
caused by the increased number of
platelets during in vitro coagulation may
cause a pseudohyperkalemia in the
serum, while the true plasma potassium
level in vivo is actually within the reference
range, as shown by measuring plasma
levels and the lack of ECG changes.
Labs
Abnormal platelet function (as measured
by platelet aggregation tests with
epinephrine, adenosine diphosphate, or
collagen) may be demonstrated, but
bleeding time may be normal.
Some patients' platelet-rich plasma
aggregates spontaneously without the
addition of any of the above substances.
This indicates a propensity for thromboses
Labs
Bone marrow studies are not necessary to
establish the diagnosis but the findings of:
hypercellularity
hyperplasia of the erythroid, granulocytic and
megakaryocytic cell lines
myelofibrosis