PHAMR D INTERN
• Polycythemia is a blood disorder in which the body
produces too many blood cells as a result of a problem with
the bone marrow or an increased production of the
• Polycythemia is defined as an increase in the hemoglobin
• Often patients with polycythemia are detected through an
incidental finding of elevated hemoglobin or hematocrit
• Concern that the hemoglobin level may be abnormally high
is usually triggered at 170 g/L (17 g/dL) for men and 150
g/L (15 g/dL)for women. Hematocrit levels >50% in men or
>45% in women may be abnormal.
• Polycythemia vera (PV) is a slow-growing type of
blood cancer in which your bone marrow makes too
many red blood cells. Polycythemia vera may also
result in production of too many of the other types
of blood cells — white blood cells and platelets.
• PV is a clonal stem cell disorder in which there is an
alteration in the pluripotent progenitor cell leading
to excessive proliferation of erythroid, myeloid and
megakaryocytic progenitor cells. Over 95% of
patients with PV have acquired mutations of the
gene Janus Kinase 2 (JAK2) (kumar and clark’s clinical
• The JAK2 gene provides instructions for making a
protein that promotes the growth and division
(proliferation) of cells. This protein is part of a
signaling pathway called the JAK/STAT pathway,
which transmits chemical signals from outside
the cell to the cell's nucleus. The JAK2 protein is
especially important for controlling the
production of blood cells from hematopoietic
stem cells. These stem cells are located within the
bone marrow and have the potential to develop
into red blood cells, white blood cells, and
Mutation causes the disorder
• The problem with blood cell production associated with
polycythemia vera is caused by a change, or mutation, to DNA in a
single cell in your bone marrow. In polycythemia vera, researchers
have found this mutation to be a change in a protein switch that
tells the cells to grow. Specifically it's a mutation in the protein JAK2
(the JAK2 V617F mutation). More than 90 percent of patients with
polycythemia vera, and about half of patients with other
myeloproliferative disorders, have this mutation. Doctors and
researchers don't understand the full role of this mutation and its
implications for treating the disease.
• The DNA mutation that causes polycythemia vera occurs after
conception — meaning that your mother and father don't have it —
so it's acquired, rather than inherited from a parent. Researchers
and doctors don't know what causes the mutation.
• Some factors may increase your risk of developing
polycythemia vera :
• Age. Polycythemia vera is more common in adults
and older than 60. It's rare in people younger than
• Sex. Polycythemia vera affects men more often than
it does women.
• Family history. In some cases, polycythemia vera
appears to run in families, indicating that genetic
factors other than JAK2 may contribute to the
• In its early stages, polycythemia vera usually doesn't
cause any signs or symptoms. As the disease
progresses, the following Symptoms may be
• Itchiness, especially following a warm bath or shower
• Redness of your skin and plethoric facial appearance
• Shortness of breath
• Breathing difficulty when you lie down
• Numbness, tingling, burning or weakness in your
hands, feet, arms or legs
• Chest pain
• A feeling of fullness or bloating in your left upper
abdomen due to an enlarged spleen
• Bleeding complications, seen in approximately 1% of
patients with PV, include epistaxis, gum bleeding,
ecchymoses, and gastrointestinal (GI) bleeding.
Thrombotic complications (1%) include venous
thrombosis or thromboembolism and an increased
prevalence of stroke and other arterial thromboses.
• Abdominal pain due to peptic ulcer diseasemay be
present because PV is associated with increased
histamine levels and gastric acidity or possible Budd-
Chiari syndrome (hepatic portal vein thrombosis).
• Pruritus results from increased histamine levels
released from increased basophils and mast cells and
can be exacerbated by a warm bath or shower. This
occurs in up to 40% of patients with PV.
• Blood tests
If a person has polycythemia vera, blood tests may
• An increase in the number of red blood cellsand, in
some cases, an increase in platelets or white blood
• Elevated hematocrit measurement, the percentage of
red blood cells that make up total blood volume.
• Elevated levels of hemoglobin, the iron-rich protein in
red blood cells that carries oxygen.
• Lower than normal levels of oxygen in your blood.
• Very low levels of erythropoietin (EPO), a hormone
that stimulates bone marrow to produce new red
blood cells, because the excess red blood cells turn off
the production of EPO by the kidneys.
Bone marrow aspiration or biopsy: Examination of bone marrow shows that it's
producing higher than normal amounts of blood cells, it may be a sign of
polycythemia vera. If you have polycythemia vera, analysis of your bone marrow
or blood also may show the DNA change (JAK2 V617F mutation) that's associated
with the disease.
Polycythaemia vera (PV) – modified from
revised WHO criteria for diagnosis
• Haemoglobin >185 g/L in men, 165 g/L in women or other evidence of
increased red cell volume.
• Presence of JAK2 tyrosine kinase V617F or otherfunctionally similar
mutation such as JAK2 exon 12mutation.
• Bone marrow biopsy, showing hypercellularity for age with trilineage
growth (panmyelosis) with prominent erythroid, granulocytic and
• Serum erythropoietin level below the reference range for
• Endogenous erythroid colony (EEC) formation in vitroa
• Diagnosis requires the presence of both major criteria and one minor
criterion or the presence of the first major criterion together with two
• polycythemia vera is a chronic condition that can't be cured. Treatment focuses on
reducing the amount of blood cells in order to control signs and symptoms of the
disease and decrease the risk of complications.
• Treatment may include :
• 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 your veins. This reduces the number of blood cells and decreases your
blood volume, making it easier for your blood to function properly. How often you
need phlebotomy depends on the severity of your condition.
• 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 for you, your doctor may prescribe medications such as
hydroxyurea or anagrelide to suppress your 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 your immune system
to fight the overproduction of red blood cells.
• Low-dose aspirin. Your doctor may recommend you take a low dose of aspirin to
reduce your risk of blood clots. Low-dose aspirin may also help reduce burning
pain in your feet or hands.
• Therapy to reduce itching. If you have bothersome itching, your doctor may
prescribe medication, such as antihistamines or H-2-receptor blockers, or
recommend ultraviolet light treatment to relieve your discomfort.
• Second line therapy for PV
• Ruxolitinib (Jakafi), a JAK1/JAK2 inhibitor, was approved by the FDA in
December 2014 for the treatment of patients with polycythemia vera who
have had an inadequate response to or are intolerant of hydroxyurea.
Approval was based on data from the phase III RESPONSE trial. In this trial,
patients treated with ruxolitinib demonstrated superior hematocrit
control and reductions in spleen volume compared with best available
therapy. A greater proportion of patients on the ruxolitinib treatment arm
achieved complete hematologic remission (ie, hematocrit control and
lowered platelet count and WBC). Hematologic adverse reactions are
prevalent with ruxolitinib (incidence >20%) and include thrombocytopenia
• Ruxolitinib was initially approved in the United States in 2011 for patients
with intermediate- or high-risk myelofibrosis including primary
myelofibrosis, post-polycythemia vera myelofibrosis, and post–essential
• Harrison’s Principle Of Internal Medicine
• Kumar and Clark’s Internal Medicine
• Netters illustrated pathology
• Guyton and Hall Textbook of Medical Physiology