ANEMIA: INADEQUATE RED BLOOD CELLS
BONE MARROW SUPPRESSION
One of the functions of the kidney is the production of the hormone called “erythropoietin” (pronounced “Urithro-po-eetin”). This hormone, often simply referred to as “Epo,” represents the command to the bone marrow to make more red blood cells. When the kidney is damaged, its ability to produce erythropoietin is compromised. Red cells are still produced but over time the red cell count drops.
Blood sample in a PCV tube being read against a chart.
A simple measurement of red blood cell count is called the “packed cell volume” or “PCV.” The packed cell volume is an expression of the percentage of the blood’s volume which is taken up by red blood cells. It can be measured using only a drop or two of blood and can be done “while you wait” in any veterinary office. The sample is spun in a machine called a “centrifuge” to separate the red cells, white cells, and serum. The blood tube is then read against a chart to get the packed cell volume.
Alternatively, hematocrit or HCT can be evaluated by biochemically measuring the amount of hemoglobin in the sample using a blood analyzer. Both measurements are common in most small animal hospitals and testing can be performed in a few minutes while you wait.
How often does this happen? n a presentation by Dr. Sheri Ross at the 2006 meeting of the American College of Veterinary Internal Medicine, she noted that in one study of dogs and cats with naturally occurring kidney failure, two of three dogs treated with erythropoietin for greater than 90 days and five of seven cats treated for greater than 180 days developed refractory anemia that was attributed to anti-erythropoietin antibodies. A clinically significant immunologic reaction to erythropoietin has been reported to occur in 20-70% of treated veterinary patients. A more commonly published statistic is that antibody production is a problem in 30-40% of pets using human erythropoietin but this complication poses a sobering thought. It is important not to use this hormone at the first sign of anemia but wait until it is really and truly needed.
Is Darbepoetin better than Erythropoietin?
Darbepoetin is a synthetic hormone meant as an improvement over the natural hormone, erythropoietin. The synthetic version lasts longer so is typically only used weekly. Less frequent use makes the product less likely to create the antibody problem described above. The cost of darbepoetin is substantially higher than for erythropoetin but ends up being similar given that darbepoeitin is used less frequency (i.e. the bottle costs much more but it lasts much longer). Why doesn't darbepoeitin have the same problem with antibodies as human erythropoietin? For one thing, darbepoetin is used much less frequently so immunological exposure to the non-feline protein is reduced. For another, it appears that the changes in the amino acid sequence have made darbepoeitin less likely to generate anti-erythropoietin antibodies. Still, in a patient that is already having issues with antibodies, darbepoietin is likely close enough to be inactivated as well.
For further information on Erythopoietin click here.
The calcium-phosphorus imbalance that goes with renal disease is reviewed elsewhere in this center but the bottom line is that the excess blood phosphorus that results in renal insufficiency leads to demineralization of bone and mineral deposits in soft tissues. Mineralization is inflammatory and, when it occurs in the GI tract, it leads to bleeding, ulceration, and pain. The renal patient cannot afford appetite loss, nausea or further blood loss so special treatment is needed while other efforts are made to control phosphorus levels.
Beyond the phosphorus level, another problem is a hormone called “gastrin.” Gastrin is a hormone involved in food digestion and is a stimulus for the stomach to release acid. Normally, when the need for gastrin has passed, the kidney removes it from the circulation but in the kidney patient gastrin is not efficiently removed. The prolonged presence of gastrin also prolongs the stomach’s secretion of acid which can lead to ulceration.
How do we know there is stomach/intestinal ulceration?
There are several clues on the lab work an in the patient’s physical appearance that tell us that additional therapy is needed to control this kind of blood loss.
What can we do?
Medications for nausea and appetite stimulation can be used. The most important treatment, of course, is going to be control of the phosphorus level. Other treatments include the following:
Pets presenting to the vet’s office in Stage IV or late Stage III kidney failure are often dehydrated. A typical scenario is a pet that had been drinking lots of water and eating fairly well suddenly stops eating and is listless. Possibly it is even noticeable that the pet has lost weight (though this is often erroneously attributed to age). The owner waits a day or two to see if the pet will start eating again and get better on its own and when that does not happen, the pet is brought to the vet. Once the diagnosis of kidney failure is made, fluid therapy will be recommended, possibly fairly aggressively to drive the toxin levels down quickly. When blood tests are rechecked, anemia that was not originally present may be apparent or an anemia that was present originally may be worse.
Are the fluids making the patient anemic? No. The patient is just as anemic as he or she was prior to fluid therapy but with the correction of the dehydration, the true red blood cell count is revealed. Hemodilution does not create anemia so much as it unmasks anemia.
What can be done?
What we do not want to do is withhold fluids from a dehydrated patient. The first step in restoring or at least maximizing kidney function is to see to it that the kidneys get the blood supply they need and that means no dehydration can be permitted. If the patient is significantly anemic (either before or after rehydration) then they may need a blood transfusion to get their red cell count back to a more livable level quickly. Restoration and maintenance of the red cell count is part of the art of managing renal disease. If your pet requires red blood cell support, this will be discussed and included in your pet's regimen.