POLYCYTHEMIA VERA

Dela Cruz, Adrian Kristopher

Managuelod, Lu
Panangon, Lourdes
Pangan, Jessa
Patayan, Haydee
BACKGROUND OF
DISEASE
Background of Disease
• Polycythemia vera was first reported in the medical
literature in 1892.
• Sir William Osler first described polycythemia rubra vera
(PV) in 1910. The clinical description was that of a patient
with engorged veins, plethora, and an elevated red blood
cell count. Leukocytosis and thrombocythemia were
recognized as additional features.
• In 1951, Dameshek added PV to the classifi cation of
MPNs. PV is a rather common disease, and the main
differential diagnosis is that of reactive erythrocytosis due
to hypoxia. The term "myeloproliferative disorder" (MPD)
was then first used to described polycythemia vera and
related disorders in this year.
• In 2008, the World Health Organization reclassified
"myeloproliferative disorder" (MPDs) to
"myeloproliferative neoplasms" (MPNs) to reflect the
consensus that these diseases are blood cancers
(neoplasms).
• Polycythemia vera (PV) is a neoplastic clonal
myeloproliferative disorder that commonly manifests
with panmyelosis in the bone marrow and increases in
erythrocytes, granulocytes, and platelets in the
peripheral blood.
• Splenomegaly is common.
• The disease arises in a hematopoietic stem cell. The
hypothesis of a clonal origin for PV is supported by
studies of X-linked restriction fragment-length
deoxyribonucleic acid (DNA) polymorphisms that
demonstrate monoclonal X chromosome inactivation in
all blood cells.
Background of Disease
 A disorder characterized by the excessive
proliferation of the erythroid, granulocytic and
megakaryocytic cell lines
 At onset, this disease is characterized by an
absolute increase in RBCs, WBCs, and
platelets.
 Gives rise to an increased blood volume that
may measure 2 to 3 times normal.
INCIDENCE
Incidence
 The disorder is estimated to affect
approximately 2 people per 100,000 in the
general population.
Some factors may increase your risk of
developing polycythemia vera:
 AGE
Polycythemia vera occurs most often in
individuals more than 60 years old, but can
affect individuals of any age. It is extremely
rare in individuals under 20.
 SEX
It affects men more often than women.
 FAMILY HISTORY
In some cases, polycythemia vera appears
to run in families, indicating that genetic
factors other than JAK2 may contribute to
the disease.
PATHOLOGY OF
DISEASE
Classifications of Polycythemia:
1. Relative Polycythemia
 decrease in plasma volume while the total
number of circulating erythrocytes remains the
same.
 almost always caused by dehydration
 Acute Dehydration:
• Burns
• Prolonged vomitings
• Crushing-type injuries
• Fevers
 Chronic Dehydration
• Decrease oral fluid intake
• Excessive diuretics
• Cigarette Smoking
Classifications of Polycythemia:
2. Absolute Polycythemia- occurs when more
RBCs are produced than normal and their count is
truly elevated.
a. Primary- is caused by an abnormality of the
cells in the bone marrow that form RBCs.
• Chronic myeloproliferative disorder

b. Secondary- is caused by an increased

production of erythropoietin resulting in an
overproduction of red blood cells.
• Chronic hypoxia
• Carboxyhemoglobinemia
• Chronic corticosteroid use
• Cardiopulmonary diseases
Pathology of Disease

I. GENETIC BASIS
 Mutations of the Janus kinase 2 (JAK2 )
gene are responsible in most cases of
polycythemia vera.
 JAK2 is a member of the tyrosine kinase
family of enzymes and is involved in signal
transduction for erythropoietin,
thrombopoietin, and granulocyte colony-
stimulating factor (G-CSF).
 Specifically, the JAK2V617F mutation or the
JAK2 exon12 mutation is present in most
patients with polycythemia vera.
Pathology of Disease

I. GENETIC BASIS
 A valine to phenylalanine substitution at
position 617 of the JAK2 gene, or
JAK2V617F, leads to constitutively active
cytokine receptors.
 These mutations lead to sustained activation
of the JAK2 kinase, which causes excess
blood cell production independent of
erythropoietin.
 This mutation is observed in over 90% of
patients with PV, as well as 50% to 60% of
primary myelofibrosis and 50% of essential
thrombocythemia.
Pathology of Disease
 Polycythemia vera involves increased
production of red blood cells (RBCs), white
blood cells (WBCs), and platelets.
 RBC production proceeds independently of
the EPO level.
 Iron deficiency may eventually occur
because of the increased need for iron to
produce RBCs.
HISTOPATHOLOGY
I. PERIPHERAL BLOOD
A. Pre-polycythemia and Overt
polycythemia
 normochromic and normocytic red blood
cells are seen
B. Post-polycythemic stage
 myelofibrosis develops with teardrop red
blood cells, poikilocytosis, and circulating
nucleated red cells
B. In the presence of Iron Deficiency
 hypochromic and microcytic can be seen
HISTOPATHOLOGY
II. BONE MARROW
A. Pre-polycythemia
 Erythrocytosis
B. Overt-polycythemic stage
 increased red cell mass
C. Post-polycythemic stage
 increased reticulin deposition
 with fibrosis, ineffective production, and
extramedullary hematopoiesis
SIGNS AND SYMPTOMS
Signs and Symptoms
The signs and symptoms of PV include:
 Headache, dizziness, and weakness
 Shortness of breath
 Feelings of pressure or fullness on the left side of the
abdomen due to an enlarged spleen
 Double or blurred vision and blind spots 
 Reddened face and a burning feeling on your skin
(especially your hands and feet)
 Bleeding from your gums and heavy bleeding from small
cuts
 Unexplained weight loss
 Fatigue (tiredness)
 Excessive sweating
 Very painful swelling in a single joint, usually the big toe
(called gouty arthritis)
Polycythemia Vera Complications
 The thickness of your blood and the slowed blood
flow can cause serious health problems.
 Blood clots (heart attack/stroke, angina, heart failure)
 Myelofibrosis
 bone marrow is replaced with scar tissue
 acute myelogenous leukemia (AML)
 Abnormal bone marrow cells growing out of control
 cancer of the blood and bone marrow
Diagnosis
• World Health Organization Criteria for the
Diagnosis of Polycythemia Vera Diagnosis
requires the presence of both major
criteria and one minor criterion or the
presence of the first major criterion
together with two minor criteria.
Major Criteria:

1. Hemoglobin (18.5 g/dL in men), (16.5

g/dL in women) or other evidence of
increased red blood cell volume.
2. Presence of JAK2 V617F or other
functionally similar mutation such as
JAK2 exon 12 mutation.
Minor Criteria

1. Bone marrow biopsy specimen showing

hypercellularity for age with trilineage
growth (panmyelosis) with prominent
erythroid, granulocytic, and
megakaryocytic proliferation
2. Serum erythropoietin level below the
reference range for normal
3. Endogenous erythroid colony formation in
vitro
Additional diagnostic features of
PV include:

 An arterial oxygen saturation of 92%

(normal) or greater
 Splenomegaly
 Hepatomegaly
LABORATORY DIAGNOSIS
HGB>16g/dL, HCT>48%, ↑↑↑RBC COUNT,
↑↑WBC COUNT, ↑↑↑PLT COUNT
BONE MARROW BIOPSY
 reveals a generalized hypercellular tissue with
the notable absence of iron stores.
RADIOLOGY
 in cases of EPO-secreting neoplasms, to rule
out Abnormal Secondary Absolute Polycythemia
vera
ABG AND OTHER TESTS
 O2 Saturation > 92%
 to differentiate from compensatory Secondary
Absolute Polycythemia
↓↓↓EPO level
Principles of
Management
1. Phlebotomy
This is usually the first treatment option for
most people with polycythemia vera.
Phlebotomy involves drawing a certain
amount of blood from one of the veins. This
reduces the number of blood cells and
decreases the blood volume, making it
easier for the blood to function properly.
How often the patient needs phlebotomy
depends on the severity of your condition.
THERAPEUTIC PHLEBOTOMY
 Aims to keep HCT values below 45%
2. Medication to decrease blood
cells.
Phlebotomy alone may not be enough to control the
signs, symptoms and complications of polycythemia
vera in some people.
• If this is the case, then medications such
as hydroxyurea or anagrelide to
suppress the bone marrow's ability to
produce blood cells.
• Radioactive phosphorus (32p) also can
be used to reduce the number of red
blood cells.
• Interferon-alpha may be used to
stimulate the immune system to fight the
overproduction of red blood cells.
3. Low-dose aspirin.
 Aspirin to reduce your risk of blood clots.
Low-dose aspirin may also help reduce
burning pain in feet or hands.
 81mg daily, unless contraindicated
by a major bleeding or gastric
intolerance. This aims to reduce the
risk of fatal thrombotic events.
4. Therapy to reduce itching.
 Antihistamines or H-2-receptor blockers,
or ultraviolet light treatment to relieve
discomfort.
References
 https://rarediseases.org/rarediseases/polycythemia
vera/?
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GBZ_6JHolGIL9xvW77MqtHJpZ4KI#:~:text=Polyc
ythemia%20vera%20affects%20slightly
%20more,rare%20in%20individuals%20under
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 https://
www.nhlbi.nih.gov/health-topics/polycythemia-vera
 https://www.ncbi.nlm.nih.gov/books/NBK557660/
 https://www.msdmanuals.com/professional/hemato
logy-and-oncology/myeloproliferative-
disorders/polycythemia-vera
 Henry's Clinical Diagnosis and Management by La
boratory Methods 22nd Edition