Brand Names: Epogen, Procrit, and Eprex

Available in 1 cc injection vials

Background

The importance of oxygen to our bodies goes without saying; virtually all our organs and tissues need oxygen in order to function properly and effectively. Oxygen is carried to our tissues by red blood cells, and we need a certain number of functioning red blood cells to keep our bodies going. When we lose red blood cells and need more, a hormone called erythropoietin is produced. This hormone instructs the bone marrow to step up the production and release of red blood cells so that we can respond to blood loss appropriately. More erythropoietin means more red blood cells, which in turn means more oxygen carried. A dose of erythropoietin lasts about a day, but its effect is seen approximately five days later when the red cell proliferation it has induced is mature enough for release into circulation.

Erythropoietin is a protein and its amino acid sequence was first mapped out in 1983. By 1985, human erythropoietin was being manufactured commercially using recombinant DNA technology and used for the treatment of anemia (low red blood cell count) in human dialysis and cancer patients. Before long, some synthetic changes improving upon the natural hormone were being added. The binding of erythropoietin with sugars, called glycosylation, slows the clearance of erythropoietin from the body, thus allowing the hormone to last longer. Glycosylated erythropoietin comes in three forms: alpha, the most commonly used type in veterinary medicine; beta, which has similar clinical efficacy to alpha; and darbepoetin, which is particularly heavily glycosylated and lasts the longest.

Approximately 85–90% of the body's natural erythropoietin comes from the kidney, and 10–15% is contributed by the liver. When the kidneys are damaged, erythropoietin production suffers, and it may become necessary to begin injections of one of the products listed above.

How this Medication is Used

In animals, erythropoietin has one major use: to treat anemia due to chronic renal disease. Since most erythropoietin is produced by the kidney, it makes sense that a damaged kidney cannot produce normal amounts of erythropoietin, and anemia results. Erythropoietin injections are effective and easy to administer by owners at home. The resolution of anemia leads to a better appetite, more energy, and higher life quality.

Erythropoietin is given by subcutaneous injection initially three times a week in conjunction with an iron supplement. The red cell count is measured weekly at first, and the dose is modified accordingly. Most patients achieve a normal red blood cell count within the first four weeks of therapy. Many patients can be maintained on weekly injections after that.

It is tempting to use erythropoietin for any anemia to which the bone marrow is not adequately responding. Results are mixed with this practice as in most such cases where the marrow is not responsive, there are healthy kidneys producing large amounts of erythropoietin already in response to the anemia. Giving yet more erythropoietin is unlikely to be beneficial as, for these cases, lack of marrow stimulation is not the problem; the problem is that the marrow cannot respond.

The most common method of monitoring red blood cell count is via a test called a packed cell volume or hematocrit, as these tests are readily run in the hospital without sending samples to an outside laboratory. The value obtained reflects the percentage of blood volume taken up by red blood cells. A normal test result for a dog would be approximately 35-60% (depending on age and gender). Normal for a cat is 29-50%. Because of the potential for antibody production against human-origin erythropoietin, it is important to withhold use until it is truly warranted rather than beginning it at the first sign of anemia. Furthermore, there is actually quite a bit more to anemia in kidney patients than lack of erythropoietin. Multiple issues are at work:

• The build-up of renal toxins causes ulceration of the GI tract, and bleeding may result.
• Red blood cells do not have normal life spans in the presence of high levels of circulating renal toxins.
• Many renal toxins directly suppress the bone marrow’s ability to produce red blood cells.
• The kidney has poor production of erythropoietin.

The point is that erythropoietin use is part of a bigger therapy picture. For more details, see renal anemia.

Side Effects

Because commercial erythropoietin and darbepoetin are human proteins, the main adverse event to be concerned about is antibody production. Antibodies are generated in response to an alien protein in the body. The problem is that antibodies that are generated not just against the alien (human) erythropoietin but also against the patient’s natural erythropoietin. This makes for profound anemia (via what is called pure red cell aplasia or PRCA), which can only be treated with blood transfusions. Regular monitoring to check for a sudden drop in red cell count is crucial as this is the sign that a problem is incipient and the product can be stopped while there is still time.

After discontinuing erythropoietin, antibodies wane over two to 12 months, and the red cell count returns to its pre-treatment level. Blood transfusions may be needed to keep the patient alive during this time.

It has been proposed that the heavily glycosylated version of the hormone (darbepoetin; brand name Aranesp®) is less likely to cause this reaction than other recombinant erythropoietin since it differs from the human product the most, contains no human albumin, and requires less frequent use. Darbepoetin costs substantially more than erythropoietin but the cost is offset by the less frequent use and may be a safer alternative.

A high percentage of patients (approximately 50%) on red cell-producing hormones develop high blood pressure.

It is thought that this occurs when the red cell count gets too high, and the blood becomes abnormally viscous. Blood pressure medications can be used to control this and the erythropoietin dose can be modified to reduce the red cell count.

Interactions with Other Drugs

It is important to administer an iron supplement in conjunction with the erythropoietin injections so that the bone marrow will have all the necessary supplies with which to make red blood cells. A multivitamin with iron is typically used as this will also provide the B vitamins needed.

In humans, carnitine administration improves the response to erythropoietin in some individuals. Carnitine is a nutritional supplement available at most vitamin stores.

Concerns and Cautions

As discussed above, the main concern is developing antibodies and subsequent anemia. Monitoring is important with erythropoietin use, and it may be worthwhile to consider darbepoetin as an alternative.  At this time, the amino acid sequence of the canine and feline versions of erythropoietin are known but commercial products are not available. Obviously, commercially available dog or cat erythropoietin would preclude the above antibody issues.

Proper injection technique is important. Be sure you understand how to give the injections and use the needles necessary. An injection into your pet’s fur is not helpful.

Certain regions (California is one) require specific disposal precautions for needles used at home. Be sure you know the regulations in your area.

The bottle of erythropoietin must be refrigerated all the time. If a dose is accidentally skipped, give it when remembered and reschedule the next injection accordingly. Do not double up on the next dose.