POLYCYTHEMIA VERA

Polycythemia is an increased number of red blood cells in the blood. In polycythemia, the levels of
hemoglobin (Hgb), hematocrit (Hct), or the red blood cell (RBC) count may be elevated when measured
in the complete blood count (CBC), as compared to normal.

Hemoglobin levels greater than 16.5 g/dL (grams per deciliter) in women and greater than 18.5 g/dL in
men suggest polycythemia. In terms of hematocrit, a value greater than 48 in women and 52 in men is
indicative of polycythemia.

Production of red blood cells (erythropoiesis) occurs in the bone marrow and is regulated in a series of
specific steps.

One of the important enzymes regulating this process is called erythropoietin (Epo). The majority of Epo
is produced and released by the kidneys, and a smaller portion is released by the liver.

Polycythemia can result from internal problems with the production of red blood cells. This is termed
primary polycythemia. If polycythemia is caused due to another underlying medical problem, it is
referred to as secondary polycythemia.

Most cases of polycythemia are secondary and are caused by another medical condition. Primary
polycythemias are relatively rare.

One percent to five percent of newborns can have polycythemia (neonatal polycythemia).

What Are the Symptoms of Polycythemia?

Symptoms of polycythemia can vary widely. In some people with polycythemia, there may be no
symptoms at all.

In secondary polycythemia, most of the symptoms are related to the underlying condition responsible for
polycythemia.

Symptoms of polycythemia vera can be vague and quite general. Some of the important symptoms
include:
easy bruising;

easy bleeding;

blood clot formation (potentially leading to heart attacks, strokes, blood clots in the lungs [pulmonary
embolism]);

bone and joint pain (hip pain or rib pain);

headache;

itching;

itching after taking a shower or bath (post-bath pruritus);

fatigue;

dizziness; and

abdominal pain.

Causes
What Causes Primary Polycythemia?

In primary polycythemia, inherent or acquired problems with red blood cell production lead to
polycythemia. Two main conditions that belong to this category are polycythemia vera (PV or
polycythemia rubra vera [PRV]) and primary familial and congenital polycythemia (PFCP).

Polycythemia vera (PV) is related to a genetic mutation in the JAK2 gene, which is thought to increase
the sensitivity of bone marrow cells to Epo, resulting in increased red blood cell production. Levels of
other types of blood cells (white blood cells and platelets) are also often increased in this condition.

Primary familial and congenital polycythemia (PFCP) is a condition related to a mutation in the EPOR
gene and causes increased production of red blood cells in response to Epo.

What Causes Secondary Polycythemia?

Contrary to primary polycythemia in which overproduction of red blood cell results from increased
sensitivity or responsiveness to Epo (often with lower than normal levels of Epo), in secondary
polycythemia, more red cells are produced because of high levels of circulating Epo.
The main reasons for higher than normal Epo are chronic hypoxia (poor blood oxygen levels over the
long-term), poor oxygen delivery due to abnormal red blood cell structure, and tumors releasing
inappropriately high amounts of Epo.

Some of the common conditions that can result in elevated erythropoietin due to chronic hypoxia or poor
oxygen supply include:

chronic obstructive pulmonary disease (COPD, emphysema, chronic bronchitis),

pulmonary hypertension,

hypoventilation syndrome,

congestive heart failure,

obstructive sleep apnea,

poor blood flow to the kidneys, and

living in high altitudes.

2,3-BPG deficiency is a condition in which the hemoglobin molecule in the red blood cells has an
abnormal structure. In this condition, hemoglobin has a higher affinity to hold on to oxygen and is less
likely to release it to the tissues. This results in more red blood cells being produced in response to what
the tissues in the body perceive as an inadequate oxygen level. The outcome is more circulating red blood
cells.

Certain tumors have a tendency to secrete inappropriately high amounts of Epo, leading to polycythemia.
The common Epo-releasing tumors are:

liver cancer (hepatocellular carcinoma),

kidney cancer (renal cell carcinoma),

adrenal adenoma or adenocarcinoma, and

uterine cancer.

There also are more benign conditions that may cause increase Epo secretion, such as kidney cysts and
kidney obstruction.
Chronic carbon monoxide exposure can also lead to polycythemia. Hemoglobin naturally has a higher
affinity for carbon monoxide than for oxygen. Therefore, when carbon monoxide molecules attach to
hemoglobin, polycythemia (increased red cell and hemoglobin production) may occur in order to
compensate for the poor oxygen delivery by the existing hemoglobin molecules. A similar scenario can
also occur with carbon dioxide in long-termcigarette smoking.

Polycythemia in newborns (neonatal polycythemia) is often caused by transfer of maternal blood from the
placenta or blood transfusions. Prolonged poor oxygen delivery to the fetus (intrauterine hypoxia) due to
insufficiency of the placenta can also lead to neonatal polycythemia.

What Is Relative Polycythemia?

Relative polycythemia describes conditions in which red cell volume is high due to increased blood
concentration of red cells as a result of dehydration. In these situations (vomiting, diarrhea, excessive
sweating) the number of red blood cells is normal, but because of the fluid loss affecting the blood
(plasma), red blood cell counts may seem elevated.

What Is Stress Polycythemia?

Stress erythrocytosis (also known as pseudopolycythemia or Gaisbock's syndrome) is seen in obese
middle aged men who are being treated with a diuretic medication for hypertension. It is not unusual that
such men are also cigarette smokers.

What Are the Risk Factors for Polycythemia?

Some of the risk factors for polycythemia include:

chronic hypoxia;

long-term cigarette smoking;

familial and genetic predisposition;

living in high altitudes;

long-term exposure to carbon monoxide (tunnel workers, car garage attendants, residents of highly
polluted cities); and

Ashkenazi Jewish ancestry (may have increased frequency of polycythemia vera due to genetic
susceptibility).

When Should I Call the Doctor About Polycythemia?

People with primary polycythemia need to be aware of some of the potentially serious complications that
may occur. The formation of blood clots (heart attacks, strokes, blood clots in the lungs [pulmonary
embolism] or legs [deep vein thrombosis]) and uncontrolled hemorrhaging (nosebleeds, gastrointestinal
bleeding) typically require prompt medical attention by the treating physician or emergency department.

Patients with primary polycythemia are usually cared for by their primary care physicians, internists,
family physicians, and hematologists (doctors who specialize in blood disorders).

Conditions leading to secondary polycythemia can be managed by primary care physicians and internists
in addition to specialists. For example, people with long- standing lung disease may routinely see their
lung doctor (pulmonologist) and those with chronic heart disease may see their heart doctor (cardiologist).

What Are the Exams and Tests Used to Diagnose Polycythemia?

In the majority of instances, polycythemia may be detected incidentally in routine blood work ordered by
a physician for an unrelated medical reason. This may then prompt further investigation to find the cause
of polycythemia.

In evaluating a patient with polycythemia, a comprehensive medical history, physical examination, family
history, and social and occupational history are very important. In the physical exam, special attention
may be paid to the heart and lung exam. An enlarged spleen (splenomegaly) is one of the prominent
features of polycythemia vera; therefore, a careful abdominal exam to evaluate for an enlarged spleen is
important.

Polycythemia vera treatment

PV is a chronic condition that doesn’t have a cure. However, treatment can help you manage its
symptoms and help prevent complications. Your doctor will prescribe a treatment plan based on your risk
of developing blood clots.

Treatment for low-risk people

Typical treatment for those at low risk of blood clots includes two things: aspirin and a procedure called
phlebotomy.
Low-dose aspirin. Aspirin affects the platelets in your blood, decreasing your risk of forming blood clots.

Phlebotomy. Using a needle, your doctor will remove a small amount of blood from one of your veins.
This helps reduce your red blood cell count. You’ll typically have this treatment about once a week, and
then once every few months until your hematocrit level is closer to normal.

Treatment for high-risk people

In addition to aspirin and phlebotomy, people at high risk of blood clots may require more specialized
treatment, such as other medications. These can include:

Hydroxyurea (Droxia, Hydrea). This is a cancer drug that prevents your body from making too many
red blood cells. It reduces your risk of blood clots. Hydroxyurea is used off-label to treat PV.

Interferon alpha. This drug helps your immune system fight off the overactive bone marrow cells that
are part of PV. It can also block your body from making too many red blood cells. Like hydroxyurea,
interferon alpha is used off-label to treat PV.

Busulfan (Myleran). This cancer drug is approved to treat leukemia, but it can be used off-label to treat
PV.

Ruxolitinib (Jakafi). This is the only drug approved by the U.S. Food and Drug Administration to treat
PV. Your doctor may prescribe this drug if you can’t tolerate hydroxyurea, or if hydroxyurea doesn’t
lower your blood count enough. Ruxolitinib works by inhibiting growth factors responsible for creating
red blood cells and immune system functioning.

Related treatments
Your doctor may also prescribe other treatments for you. Some of these may help relieve itching, which
can be a persistent and bothersome problem for many people with PV. These treatments may include:

antihistamines

selective serotonin reuptake inhibitors (SSRIs)

phototherapy (treatment with ultraviolet light)

Your doctor will talk with you about the best treatment options for you. Explore questions you can ask
your doctor about treatment for polycythemia vera.
Polycythemia vera diet
In general, the diet recommended for people with PV is the same as it is for anyone. Eat well-balanced
meals complete with fresh fruits and vegetables, whole grains, lean protein, and low-fat dairy. Ask your
doctor how many calories you should consume each day to maintain a healthy weight.

Also, watch how much salt you eat. High-sodium foods can cause your body to shift water into your
body’s tissues, which can make some of your PV symptoms worse. Also, drink enough fluids to avoid
dehydration and maintain good blood flow and circulation. Your doctor can provide individualized
guidance on diet and water intake.

Polycythemia vera prognosis

Your prognosis with PV depends largely on whether you get treatment. Treatment helps reduce your risk
of life-threatening complications, such as:

myelofibrosis: the advanced stage of PV that scars the bone marrow and can enlarge the liver and spleen

heart attack

deep vein thrombosis (DVT)

ischemic stroke: a stroke caused by loss of blood supply to the brain

pulmonary embolism: a blood clot in the lung

hemorrhagic death: death from bleeding, usually from the stomach or other parts of the digestive tract

portal hypertension: increased blood pressure in the liver that can lead to liver failure

acute myeloid leukemia (AML): a particular type of blood cancer that affects white blood cells

These complications from PV are possible even with treatment, but the risk is much lower. For people
with PV, just 5 to 15 percentTrusted Source have typically developed myelofibrosis 15 years after
diagnosis. And less than 10 percent have typically developed leukemia 20 years after diagnosis. Overall,
people who receive treatment have a much better outlook than those without it.

In addition, taking care of yourself and your overall health can lower your risk of blood clots from PV.
Quitting smoking, staying physically active, and managing other health conditions you have, such as
diabetes, high blood pressure, and heart disease, can also improve your outlook. Learn more about
polycythemia vera prognosis.
Polycythemia vera life expectancy
Everyone’s situation with PV is different. But many people who stick to their treatment plan and see their
hematologist regularly can expect to live a long life with limited complications.

Treatment is critical. People without any treatment can typically expect to survive less than two years,
depending on age and overall health. But those who have treatment can live several more decades. The
average length of survival after diagnosis is at least 20 years, and people can live for decades longer.
Learn more about polycythemia vera life expectancy.

Routine blood work including a compete blood count (CBC), clotting profile, and metabolic panel are
basic components of laboratory tests in assessing the cause of polycythemia. Other typical tests to
determine the potential causes of polycythemia include chest X-rays, electrocardiogram (ECG),
echocardiogram, hemoglobin analysis, and carbon monoxide measurement.

In polycythemia vera, usually other blood cells are also affected, represented by an abnormally high
number of white blood cells (leukocytosis) and platelets (thrombocytosis). Bone marrow examinations
(bone marrow aspiration or biopsy) are sometimes necessary to examine blood cell production in the bone
marrow. Guidelines also recommend checking for the JAK2 gene mutation as a diagnostic criterion for
polycythemia vera.

Checking Epo levels are not required, but these can sometimes provide helpful information. In primary
polycythemia, the Epo level is typically low, whereas in Epo-secreting tumors, the level may be higher
than normal. The results need to interpreted carefully as the Epo level may be appropriately high in
response to chronic hypoxia, if that is the underlying cause of polycythemia.

What Is the Treatment of Polycythemia?

The mainstay of therapy for polycythemia vera remains phlebotomy (blood letting). The goal of
phlebotomy is to keep the hematocrit around 45% in men and 42% in women. Initially, it may be
necessary to do phlebotomy every 2 to 3 days and remove 250 to 500 milliliters of blood each session.
Once the goal is reached, maintenance phlebotomy can be performed less frequently.
A commonly recommended medication for the treatment of polycythemia is called hydroxyurea (Hydrea).
This is especially advised in people at risk of clot formation. At age greater than 70, having both an
elevated platelet count (thrombocytosis) greater than 1.5 million and cardiovascular disease makes the use
of hydroxyurea more favorable. Hydroxyurea is also recommended in patients who are unable to tolerate
phlebotomy. Hydroxyurea can lower all elevated blood counts (WBC, red blood cells, and platelets),
whereas phlebotomy only lowers the HCT.

Aspirin has also been used in treating polycythemia to lower the risk of clotting (thrombotic) events. Its
use is generally avoided in those people with any bleeding history. Aspirin is usually used in conjunction
with phlebotomy.

What Is the Treatment for Secondary Polycythemia?

Treatment of secondary polycythemia depends on its cause.

Supplemental oxygen can be provided for individuals with chronic hypoxia.

Other therapies can be directed toward treating the cause of polycythemia (for example, appropriate
treatment of heart failure or chronic lung disease).

Treatments for primary polycythemia play an important role in improving the outcome of the disease.