ERYTHROPOIETIN

(for veterinary information only)

BRAND NAME: EPOGEN, PROCRIT, AND EPREX

AVAILABLE IN
1 cc INJECTION VIALS
containing
2000 units, 3000 units,
4000 units, 10,000 units,
20,000 units and 40,000 units
PER VIAL

BACKGROUND

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. Binding of erythopoietin 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 percent 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: the treatment of anemia due to chronic renal disease. Since most erythropoietin is produced by the kidney it should make sense that a damaged kidney cannot produce normal amounts of erythropoietin and anemia results. Erythropoietin injections are very effective and easy to administer by owners at home. Resolution of anemia leads to 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 4 weeks of therapy. Many patients can be maintained on weekly injections after that.

It is tempting to use erythropoeitin 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 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 results for a dog would be approximately 35-60% (depending on age and gender). Normal for a cat would be 29-50%. Because of the potential for antibody production against human origin erythropoietin, is important to withhold use until it is truly warranted rather than beginning it at the first sign of anemia. Further, 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 is very ulcerating to 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.
• Poor production of erythropoietin by the kidney.

The point is that erythropoietin use is part of a bigger therapy picture. For more details click here.

SIDE EFFECTS

Because commercial erythropoeitin 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 erythorpoietin. This makes for a 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.

(original graphic by marvistavet.com)

Because commercial erythropoeitin 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 erythorpoietin. This makes for a 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.

In one study 2 out of 3 dogs treated for more than 90 days with human erythropoietin
and 5 out of 7 cats treated for more than 180 days with human erythropoietin
developed refractory anemia due to anti-erythropoietin antibodies.
A more commonly reported statistic is a 30% incidence in development of refractory anemia
(a lower percentage but still an uncomfortably high one).

After discontinuing erythropoietin, antibodies wane over 2-12 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 erythropoietins since it differs from the human product the most, contains no human albumin, and requires less frequent use. Darbepoetin costs substantially more than erythropoeitin but the cost is offset by the less frequent use and may be a safer alternative.

Some patients 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 very 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 red cell production as well.

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 the development of antibodies and subsequent anemia. Monitoring is very important with erythropoeitin use and it may be worthwhile to consider darbepoetin as an alternative. At the present 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 special disposal precautions for needles used in the home setting. Be sure you know the regulations in your area. For information on needle disposal in California, click here.

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.

Short version (to help us comply with "Lizzie's Law")

Page last updated: 10/23/2021