Polycythemia

Polycythemia

Polycythemia Overview

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; for example, polycythemia vera occurs in approximately 1 to 2 adults per 100,000 in the United States. One percent to five percent of newborns can have polycythemia (neonatal polycythemia).

Polycythemia Primary Causes

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. 

Polycythemia Secondary Causes

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-term cigarette 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.

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.

Stress Polycythemia

This is a condition that may be seen in hardworking, anxious, middle-aged men due to low plasma volume, although the red blood cell volume may be normal. Other names for this condition are pseudopolycythemia, stress erythrocytosis, or Gaisbock's disease.

Polycythemia Risk Factors

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).

Polycythemia Symptoms

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.

When to Seek Medical Care

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).