Posts Tagged ‘red cell production’


Larry H. Bernstein, MD, FCAP, Curator


 Erythropoietin test

The erythropoietin test measures the amount of a hormone called erythropoietin (EPO) in blood.

The hormone tells stem cells in the bone marrow to make more red blood cells. EPO is made by cells in the kidney. These cells release more EPO when blood oxygen levels are low.


The Story of Erythropoietin

Millions of patients worldwide have benefited from research on erythropoietin spanning many decades. In the last 15 years, epoetin alfa (Epo) has become one of the most widely used drugs created through recombinant DNA technology, in which a nearly identical form of a substance that naturally occurs in the body – in this case, erythropoietin – is created by replicating human DNA in a laboratory. Epo is used to treat anemia, a shortage of red blood cells. Since red blood cells carry oxygen to the tissues and organs, anemia causes symptoms such as weakness, fatigue, and shortness of breath. Epo treats this condition by imitating the action of the hormone erythropoietin, stimulating the body to produce more red blood cells. Patients who may benefit from Epo therapy include those with chronic kidney disease, those who are anemic from AIDS or from a wide variety of hematologic disorders (including multiple myeloma and myelodysplastic syndromes), and some cancer patients who are anemic from receiving chemotherapy. In selected patients, Epo may be used to reduce the need for blood transfusions in surgery.

A century ago, two French investigators reported that small amounts of plasma from anemic rabbits injected into normal animals caused an increase in red blood cell production (erythropoiesis) within a few hours. They referred to this activity as hemopoietine. Over time, as investigators became more convinced that this red-blood-cell stimulating activity was caused by a single protein in the blood plasma, they gave it a variety of names – erythropoietic-stimulating activity, erythropoietic-stimulating factor, and, ultimately, “erythropoietin.”

It wasn’t until the 1950s and ’60s that several American investigators again took up the concept that a hormone regulated red cell production. Refining the work of the French scientists, the American investigators conclusively showed that a hormone stimulated red cell production, that the kidneys were the primary source of erythropoietin, and that low oxygen was the main driver of erythropoietin production. Soon, researchers found that patients with anemia responded by increasing their levels of erythropoietin to stimulate increased red blood cell production. Patients who required an increase in red blood cells in order to make up for low oxygen levels in the blood (such as patients with lung disease or patients living at high altitudes) also had elevated erythropoietin levels.

At the same time, other technologies were being developed that set the stage for a remarkable breakthrough involving a combination of medical and molecular engineering. In the early 1960s came the development of hemodialysis, a method of removing waste products from the blood when the kidneys are unable to perform this function, to sustain the lives of patients with end-stage kidney disease. As a result of this treatment advance, these patients were able to survive the underlying disease, but their damaged kidneys could no longer make erythropoietin, leaving them severely anemic and in desperate need of Epo therapy.

In 1983, scientists discovered a method for mass producing a synthetic version of the hormone. Experiments were conducted to test the safety and effectiveness of the new drug, Epo, for treating anemia in patients with kidney failure. The results of these early clinical trials were dramatic. Patients who had been dependent on frequent blood transfusions were able to increase their red blood cell levels to near-normal within just a few weeks of starting therapy. Patients’ appetites returned, and they resumed their active lives. It was the convergence of two technologies – long-term dialysis and molecular biology – that set the stage for anemia management in this group of patients. Since then, millions of patients worldwide have benefited from Epo therapy.

This article was published in December 2008 as part of the special ASH anniversary brochure,50 Years in Hematology: Research That Revolutionized Patient Care.


Erythropoietin Stimulating Agents


What is erythropoietin?

Red blood cells are produced in the bone marrow (the spongy tissue inside the bone). In order to make red blood cells, the body maintains an adequate supply of erythropoietin (EPO), a hormone that is produced by the kidney.

EPO helps make red blood cells. Having more red blood cells raises your hemoglobin levels. Hemoglobin is the protein in red blood cells that helps blood carry oxygen throughout the body.

Anemia is a disorder that occurs when there is not enough hemoglobin in a person’s blood. There are several different causes of anemia. For instance, anemia can be caused by the body’s inability to produce enough EPO to make red blood cells. If this is the case, the person may have to have a blood transfusion to treat this type of anemia. If you have anemia, your physician can determine the cause.

What is recombinant erythropoietin?

In cases where transfusions are not an option—for example, when the patient cannot have, or refuses, a transfusion—it may be necessary to give the patient recombinant erythropoietin. Recombinant erythropoietin is a man-made version of natural erythropoietin. It is produced by cloning the gene for erythropoietin.

Recombinant erythropoietin drugs are known as erythropoietin-stimulating agents (ESAs). These drugs are given by injection (shot) and work by stimulating the production of more red blood cells. These cells are then released from the bone marrow into the bloodstream.

There are two ESAs on the U.S. market: epoetin alfa (Procrit,® Epogen®), and darbepoietin alfa (Aranesp®).

Who receives ESAs?

ESAs are usually given to patients who have chronic (long-lasting) kidney disease or end-stage renal (kidney) disease. These patients usually have lower hemoglobin levels because they can’t produce enough erythropoietin.

ESAs are also prescribed for patients who have cancer. These patients often have anemia, which can be caused by chemotherapy.

What are the side effects of ESAs?

The side effects that occur most often with ESA use include:

  • High blood pressure
  • Swelling
  • Fever
  • Dizziness
  • Nausea
  • Pain at the site of the injection.

What should the patient consider before using ESAs?

There are several safety issues with ESAs:

  • ESAs increase the risk of venous thromboembolism (blood clots in the veins). A blood clot can break away from one location and travel to the lung (pulmonary embolism), where it can block circulation. Symptoms of blood clots include chest pain, shortness of breath, pain in the legs, and sudden numbness or weakness in the face, arm, or leg.
  • ESAs can cause hemoglobin to rise too high, which puts the patient at higher risk for heart attack, stroke, heart failure, and death.
  • In patients who have cancer, ESAs may cause the tumor to grow. If ESAs are used for these patients, they are usually stopped after the patient’s chemotherapy is finished.
  • The health care provider will keep an eye on the patient’s blood cell counts to make sure they do not put him or her at a higher risk. The dosing may change, depending on the patient’s needs.

Patients who have the following conditions need to consult with their health care provider if an ESA is being considered as part of the treatment plan:

  • Heart disease
  • High blood pressure
  • Porphyria (a group of diseases that are caused by enzyme deficiencies)
  • Seizures
  • An allergy to epoetin alfa or any other part of this medicine
  • Uncontrolled high blood pressure

In addition, women who are pregnant, planning to become pregnant, or breastfeeding should consult with their health care provider before taking an ESA.

Other issues to consider:

  • Transfusions may improve symptoms of anemia right away. ESAs may take from weeks to months to provide noticeable relief of the symptoms of anemia.
  • If a patient has several transfusions, he or she can develop an “iron overload,” or high iron levels. This is a serious medical problem.
  • Iron supplements are often needed for patients who are on ESAs.
  • Keep your health care provider informed about any change in your condition.
  • Check your blood pressure and heart rate as recommended by your health care provider.
  • Remain informed about the results from any blood work that is done.
  • The body may develop antibodies to an ESA. If this happens, the antibodies will block or lessen the body’s ability to make red blood cells. This could result in an anemia. It is important that the patient keep the health care provider informed of any unusual tiredness, lack of energy, dizziness, or fainting.

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