Polycythemia

What is Polycythemia?

Polycythemia, also known as erythrocytosis, means that there are too many red blood cells in the body. This is often seen through high levels of hemoglobin, the protein that carries oxygen in your blood, or a high hematocrit, the percentage of your blood that is red blood cells. These levels vary depending on factors like age, gender, elevation, ethnicity, and country, but generally shouldn’t exceed certain values.

For example, men typically shouldn’t have a red blood cell mass of more than 36 ml/kg, and women more than 32 ml/kg. Healthy adult men usually have hemoglobin levels around 16 g/dL and a hematocrit of about 47%. Adult women, especially those menstruating, usually have hemoglobin levels around 13 g/dL and a hematocrit of about 40%. For newborns, polycythemia is classified as having a hematocrit over 65% or a hemoglobin level above 22 g/dL.

A specific form of polycythemia, polycythemia vera, is an illness where the body makes too many blood cells. Even though it could involve the overproduction of any blood cells, it mainly affects the red blood cells.

Having too many red blood cells can cause the blood to become thick, leading to the risk of clots. Also, people with polycythemia vera may have an increased risk of progressing to leukemia, a type of blood cancer. Due to these risks, strategies to manage and treat this condition are necessary.

What Causes Polycythemia?

Polycythemia is a medical condition where your body has too many red blood cells. There are different types, including Spurious Polycythemia, True Polycythemia, and Neonatal Polycythemia.

Spurious Polycythemia can happen because of severe dehydration rather than having too many red blood cells. Dehydration can come from heavy vomiting or diarrhea. It also includes a condition known as Gaisbock syndrome, which is typically seen in overweight men with high blood pressure who smoke, drink excessively, or use water pills.

True Polycythemia is split further into two types, based on the levels of a substance in your blood called erythropoietin (EPO) which helps your body make red blood cells.

If you have low levels of EPO in your blood (Primary polycythemia), you might have a disorder named Polycythemia vera or a genetic disorder, Primary familial and congenital polycythemia.

If you have high levels of EPO (Secondary polycythemia), it could be due to living at high altitudes or several lung and heart conditions. These include Chronic obstructive pulmonary disease (COPD), Pickwickian syndrome, asthma, and types of heart disease leading to blood bypassing the lungs. Kidney disorders, such as kidney cysts, kidney cancer, or Bartter syndrome, could also result in higher EPO levels. Other causes might include having high levels of a blood pigment called carboxyhemoglobin from activities like smoking or working on cars in poorly ventilated spaces. Certain genetic blood disorders and tumors that produce EPO can cause this condition. Treatments like erythropoietin shots, anabolic steroids, and testosterone replacement therapy can also raise your EPO levels.

Neonatal Polycythemia is a form seen in newborns. Babies naturally have more red blood cells due to the lower oxygen levels in the womb. This condition is made more severe by the fetus’s blood having a high capacity for carrying oxygen.

Risk Factors and Frequency for Polycythemia

Polycythemia vera is a condition that is estimated to impact about 22 out of every 100,000 people. It seems to occur more often in Jewish individuals of Eastern European descent than in other Europeans or Asians. This condition tends to favor males in all racial and ethnic groups, with the male-to-female ratio being approximately 2 to 1. The most common age for Polycythemia vera to begin showing symptoms is at age 60, and it is rare to see patients with the condition under the age of 40. However, forms of polycythemia caused by blood disorders or congenital heart diseases that cause blueness of the skin are usually diagnosed in much younger patients.

• Polycythemia vera affects about 22 out of every 100,000 people.
• It is commonly found in Jewish individuals of Eastern European heritage.
• The condition is more common in males than females, with twice as many males affected.
• People are usually around 60 years old when diagnosed with Polycythemia vera.
• It’s rare to see Polycythemia vera patients under the age of 40.
• Younger patients are more likely to have polycythemia caused by blood disorders or congenital heart diseases.

Signs and Symptoms of Polycythemia

People with certain medical conditions often experience non-specific symptoms like fatigue, headaches, and dizziness. Sometimes they may have blurry vision, transient blindness, or other symptoms that signal transient ischemic attacks. Some individuals may suffer from unexplained itching, especially on their back, after a warm shower. Other symptoms could include nosebleeds, gastrointestinal bleeding, easy bruising, or non-specific abdominal pain. Ulcers are common in these patients, and they might also feel pain in their upper left abdomen or a loss of appetite which could suggest an enlarged spleen. There are also rare cases where patients have a history of unexplained blood clots, such as Budd-Chiari syndrome or digital infarcts.

• Non-specific symptoms including fatigue, headaches, dizziness
• Blurry vision or transient blindness
• Itching, particularly on the back, following a warm shower
• Nosebleeds
• Gastrointestinal bleeding or easy bruising
• Non-specific abdominal pain
• Peptic ulcer disease
• Pain in upper left abdomen and early satiety, suggesting an enlarged spleen
• Unexplained blood clots such as Budd-Chiari syndrome or digital infarcts

Other important aspects to probe include understanding if the patient has a history of smoking, has spent a lot of time at high altitudes, or if there is congenital heart disease in the family.

During a physical examination, doctors may note unusual redness on the face. Symptoms like blue discoloration, abnormal curvature and enlargement of the fingertips (clubbing), along with the presence of abnormal heart sounds may suggest that the patient is suffering from congenital cyanotic heart disease. There might be evidence of smoking present, like nicotine staining on the nails and teeth. Extreme obesity could warn doctors about the potential risk of Pickwickian syndrome, and a barrel-shaped chest may suggest a lung disease that blocks the airflow. During abdominal examination, the doctor might discover a palpable spleen or a whooshing sound upon checking a patient’s renal artery, particularly in a thin person, indicating possible renal arterial stenosis.

• Redness on face
• Blue discoloration and clubbing of fingers
• Nicotine staining on the nails and teeth
• Extreme obesity, suggesting Pickwickian syndrome
• Barrel-shaped chest, indicative of obstructive lung disease
• Palpable spleen
• Audible whooshing sound over renal artery in a slender individual, suggesting renal arterial stenosis

Testing for Polycythemia

When checking for certain health conditions, it’s important to proceed one step at a time. This is due to the wide variety of potential causes for the symptoms. Here, we’ll explain some basic tests often used in these investigations:

Hemogram

This test looks at your blood levels. According to the World Health Organization, men who have a hematocrit level (the proportion of red blood cells to the total blood volume) greater than 49% and women with a level above 48% are suspected to have polycythemia vera. This is a disorder where your body makes too many red blood cells. It could also mean an increase in platelet and white blood cell counts. For example, your white blood cell count could be between 10,000 to 20,000/microliter, with increased numbers of certain types of white blood cells called eosinophils and basophils. Platelet counts may sometimes exceed 1,000,000/microliter.

Radioisotope Studies

Doctors use these tests, which involve the transfusion of red blood cells labeled with chromium, to accurately determine the true red blood cell mass and conclusively rule out false cases of polycythemia.

Serum EPO Levels

The level of EPO (Erythropoietin, a hormone that stimulates the production of red blood cells) in your body can provide clues for the next steps in evaluation:

Low EPO levels might point to primary polycythemia. The next step would be to look for a condition called polycythemia vera. Tests for a gene mutation called JAK2, which is typically present in 95% of polycythemia vera cases, would be necessary here.

High EPO levels suggest secondary polycythemia. The following steps might include:

• Measuring arterial oxygen saturation levels: Low levels could point to a lung or heart issue.
• If normal saturation levels were observed, further tests might be needed like checking for methemoglobinemia, checking for higher than normal carbon monoxide levels in smokers, or assessing for abnormal oxygen-carrying capacity of hemoglobin in the blood.
• Conducting investigations to detect a tumor that could be increasing the production of EPO.

Serum Ferritin, Vitamin B12, and Folate Levels

Low body stores of iron (serum ferritin) and folate (a type of B vitamin) tend to be linked with primary polycythemia. High levels of vitamin B12 may also be noticed, as a result of increased secretion by white blood cells.

Assessment of Kidney and Liver Function

Abnormal kidney function could imply secondary polycythemia. Uric acid levels might be increased due to enhanced cell production and disposal. Conditions like liver cirrhosis and inflammatory liver disease can also be associated with secondary polycythemia and an increase in red blood cell production.

Ultrasound

An ultrasound and flow speed (Doppler) study of the abdomen could help identify a secondary cause for increased red blood cell count.

In cases where secondary polycythemia is suspected, other tests like chest x-rays, lung function tests, sleep studies, and heart ultrasound (echocardiogram) may also help in understanding the cause.

Treatment Options for Polycythemia

Secondary polycythemia refers to a condition where your body makes too many red blood cells. The most effective treatment for this condition is fixing the root of the issue, if it’s possible.

Polycythemia vera is a specific form of secondary polycythemia – in this situation, there are a few different possible approaches for treatment:

1. Phlebotomy: This is a procedure where blood is taken from your veins. The reasoning behind this treatment is that it can decrease the thickness of your blood and help reduce the chances of blood clots forming. This treatment is usually done weekly until your blood reaches a certain level of thickness. It can also be used for other specific forms of this condition, such as chronic lung disease, heart disease, or after a kidney transplant.

2. Hydroxyurea: This is a medication usually used as a secondary option for treatment. It can be helpful for people who don’t have good vein access for phlebotomies, need a lot of phlebotomies, have logistical issues making phlebotomy difficult, have an excessive number of platelets in their blood, or have constant itching.

3. Ruxolitinib: This medication, which blocks a protein that affects blood cells in the body, may be given to patients who don’t respond well to or have adverse reactions to Hydroxyurea. It has been proven to decrease specific symptoms and extend survival rates, but can cause an increased risk of anemia and low platelet count.

4. Low-dose aspirin: This can help keep your blood thinner and decrease your chance of having a blood clot. It’s recommended for those with certain additional cardiovascular risk factors or if other treatments aren’t adequately managing symptoms.

5. Allopurinol and febuxostat: These are medications that could be given in case your blood has too much of a certain type of acid (uric acid).

Depending on how severe your symptoms are and how well you respond to different treatments, doctors may also use antihistamines (which can help with itching and allergies) or selective serotonin reuptake inhibitors (SSRIs), which are commonly used to treat depression.

For women with polycythemia vera who are pregnant, the standard treatments of phlebotomy and low-dose aspirin are generally safe to continue with. In certain cases, doctors might add in another medication, called pegylated interferon (IFN)-alpha.

In the case of newborns with polycythemia, treatment might not be necessary. In some cases, a procedure called an exchange transfusion might be used to thin the baby’s blood.

What else can Polycythemia be?

These are some medical conditions that could be a possible diagnosis:

• Primary myelofibrosis
• Chronic myeloid leukemia
• Essential thrombocythemia
• EPO receptor mutations

What to expect with Polycythemia

Research suggests that on average, people diagnosed with polycythemia vera, a slow-growing blood cancer where your body makes too many red blood cells, can expect to live for around 14.1 years.

It’s important to mention that certain factors can influence this prognosis positively or negatively. If you have thrombocytosis (a condition where your body produces too many platelets) or pruritus (a condition that causes itchy skin), your outlook may be better. The improvement in survival seen in people with pruritus may be because itchiness tends to drive people to seek medical help sooner, or it might be because pruritus is associated with a lower risk of arterial thrombosis, a serious condition where a blood clot blocks one of your major arteries.

On the other hand, certain factors could indicate a worse outcome. These include higher leucocyte counts (having too many white blood cells), venous thrombosis (a blood clot in your veins), and a leukoerythroblastic blood smear (a blood test result that shows both immature white and red blood cells in your blood).

Possible Complications When Diagnosed with Polycythemia

Secondary polycythemia and polycythemia vera are health conditions that come with complications. For secondary polycythemia, the main issue is related to increased blood thickness. On the other hand, polycythemia vera leads to an increased risk of blood clots and can also escalate to serious conditions like cancer.

Common Complications:

• Bleeding: Recurrent nosebleeds or bleeding in the digestive tract are common. These bleeding problems can lead to anemia due to iron deficiency, which can affect other clinical signs, including the appearance of bone marrow.
• Blood Clots: Due to increased blood thickness, there is a higher likelihood of both arterial and venous blood clots. These clots can block the flow of blood to fingers and toes, and proper functioning of the brain can be disrupted, especially in certain areas. There can be venous blood clots as well, such as Budd-Chiari syndrome.
• Cancer: Progression to a type of blood cancer, specifically acute myeloid leukemia (AML) is seen in about 5% of cases and is often resistant to treatment. Some studies have linked the use of specific medications, namely chlorambucil, pipobroman, or radioactive phosphorus, with increased chances of the condition getting worse.

Preventing Polycythemia

It’s crucial for patients to quit smoking. Families of individuals dealing with hemoglobinopathies, conditions that impact the protein in red blood cells called hemoglobin, should be offered genetic counseling. This helps in understanding the disease and knowing the risks for future generations. Patients suffering from polycythemia vera, a condition causing an overproduction of red blood cells, should avoid donating blood. This is due to the disorder’s nature, as it causes an elevated number of red blood cells in the bloodstream. Consequently, the blood from these patients isn’t deemed suitable for donations in many parts of the world.