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

Epogen bottle

(original graphic by marvistavet.com)

Erythropoietin is the hormone responsible for inducing red blood cell production by the body’s bone marrow. Red blood cells are responsible for carrying oxygen to the body's tissues so when a drop in blood oxygen level is perceived, erythropoietin production steps up. Approximately 85-90% of the body's erythropoietin comes from the kidney and 10-15% is contributed by the liver. More erythropoeitin 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 5 days later when the red cell proliferation it has induced is mature enough for release into the 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. 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 3 forms: “alpha” (the most commonly used type in veterinary medicine), “beta” (of similar clinical efficacy to alpha), and darbepoetin (which is particularly heavily glycosylated and lasts the longest).

While human recombinant erythopoietin works reliably in dogs and cats, it is not quite the same protein as what a dog or cat would make for itself and in some patients the immune system of the pet can recognize the human protein as foreign. Antibodies may develop in response to its exposure which not only destroy the human erythropoietin but the pet's natural erythropoietin as well.

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 that can sometimes occur.

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.

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.

HOW THIS MEDICATION IS USED

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.

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. Normal for dogs is approximately 35-60% (depending on age and gender). Normal for cats is 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. It is important to note that 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

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 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. It has been proposed that darbepoetin (Aranesp ®) is less likely to cause this reaction than other recombinant erythropoietins since it differs from the human product the most.

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.

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.

Some patients on erythopoietin 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

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.

The bottle of erythropoietin must be refrigerated at all times.

Page last updated: 8/29/2013