Erythropoietin (EPO)

Erythropoietin, also known as EPO, is a hormone that is manufactured in the kidneys and can also be produced synthetically. It helps to stimulate the bone marrow to grow red blood cells, which help carry oxygen throughout the body. EPO is important in several ways. Measuring the level of erythropoietin in the body can help in the diagnosis of some illnesses. Erythropoietin can be administered to help increase the number of red blood cells a person's body produces. This can help treat anemia, or low red blood cell levels, that results from a number of causes. While EPO is used for many important and life-sustaining reasons, it has also been used inappropriately by some athletes to improve their performance.

Background

About 40 percent of the volume of blood in the human body is made up of red blood cells, which are also called erythrocytes. Red blood cells carry oxygen from the lungs to the rest of the body and transport waste products, including carbon dioxide, away from cells and tissue in the body. When there are not enough red blood cells, the body is deprived of the oxygen it needs to generate energy. As a result, the person often becomes tired, pale, and possibly short of breath. This is a condition known as anemia.

Anemia is caused in one of two ways. First, anemia may result if the body does not produce enough erythrocytes. This can be caused by an illness or by insufficient iron or vitamin B12 in the diet, since both are needed to produce red blood cells. The second cause is the loss or damage of blood cells. This can happen by sudden or prolonged bleeding, such as from an injury, or from illnesses such as infections, cancer, or kidney disease. Certain medications, such as those used for chemotherapy, can also impair the body's ability to make red blood cells.

Red blood cells generally live for about one hundred twenty days before they need to be replaced, and the body is continuously replenishing its supply. Some cells located in healthy kidneys are able to detect the reduction in oxygen in the blood as the red blood cell level drops and release erythropoietin to trigger the bone marrow to produce fresh cells. The kidneys produce about 90 percent of the erythropoietin the body needs; the remainder comes from the liver.

In 1906, French physician Paul Carnot and his assistant, C. Deflandre, discovered that if they took blood from an anemic rabbit and injected it into a healthy rabbit, the healthy rabbit made more red blood cells. They deduced that something in the anemic blood triggered the production of new cells. When it proved difficult to replicate their results, some doubted their hypothesis. However, in the middle of the twentieth century researchers were finally able to confirm the results of Carnot and Deflandre. Additional experiments that connected the circulatory systems of two living rats determined that if one was exposed to low oxygen conditions, both developed new red blood cells. This confirmed the existence of erythropoietin. Between 1964 and 1977, American biochemist Eugene Goldwasser was able to isolate and purify erythropoietin. This was followed in 1983 by the development of a synthetic, or man-made, version of erythropoietin.

Overview

For many years, frequent blood transfusions and the addition of iron and B12 rich foods to the diet were the only practical ways physicians had to treat anemia. The discovery of erythropoietin and the ability to produce a synthetic version radically improved treatment of the disease. It also made it possible to improve the health of people undergoing treatment for serious diseases that deplete red blood cells, such as cancer, acquired immune deficiency syndrome (AIDS), and human immunodeficiency virus (HIV).

Patients who need treatment with erythropoietin receive it by injection, which can be done into a vein (intravenously) or under the skin (subcutaneously). The drug requires a physician's order. The two forms are erythropoietin alfa, which is sold under the brand names Procrit and Epogen, and darbepoietin alfa, which is sold under the brand name Arenesp. The darbepoietin alfa format requires less frequent administration but otherwise performs in an identical manner to erythropoietin alfa. The effectiveness of either form is determined through the use of blood tests. Since it takes several weeks for new red cells to form, these tests will be done two to four weeks after the start of therapy with erythropoietin and may be repeated. A physician many adjust dosages of the drug based on the results of the blood tests.

While the drug can generate significant improvement in anemia and help prevent it in patients with other conditions that lead to anemia, erythropoietin does have a potentially serious side effect. It can cause blood clots, particularly in patients who are prone to clots, who are idle because of prolonged bed rest, who have had surgery, or who are taking certain other medications, including several chemotherapy drugs. Patients at a higher risk of developing clots may take blood thinners while on erythropoietin to minimize the chance of clot formation.

Misuse

For decades, athletes have known that increasing the body's ability to use oxygen can improve athletic performance. This is the reason athletes do wind sprints and similar exercises: to build the lungs' capacity to provide as much oxygen as possible. When erythropoietin became readily available in the late 1980s, professional athletes were quick to see its potential to artificially boost their oxygen capacity by building an abundance of oxygen-carrying red blood cells.

This led to a practice known as blood doping, in which athletes take drugs as a shortcut to improving their performance. Many professional sports leagues and associations banned the use of erythropoietin beginning in the 1990s. Erythropoietin was one of several performance-enhancing drugs used by cyclist Lance Armstrong. The revelation that he was using these drugs led to Armstrong being stripped of seven Tour de France titles and an Olympic medal in 2012. Other athletes also faced penalties after being caught misusing erythropoietin.

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