TANYA'S

 

FELINE CHRONIC RENAL FAILURE

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ANAEMIA

 

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What is Anaemia? Why does Anaemia Occur in CRF Cats? Other Causes

Support

 

 Major Symptoms and Risks

Faster Heart Rate

High Blood Pressure

Breathlessness

Weakness

Oedema (Fluid Build-Up) and Heart Failure Other Symptoms (e.g. Eating Litter) 

 

Diagnosis

Packed Cell Volume (PCV) or Haematocrit (HCT)

Reticulocytes (Regenerative and Non-Regenerative Anaemia)
Mean Cell Volume (MCV) Red Blood Cells (RBC)

 

Treatments Other than rhEpo (Epogen, Eprex or Procrit)
Iron

Correcting Vitamin B Deficiencies

Anabolic Steroids

Blood Transfusions

Feline Erythropoietin (Not Currently Available) Making Your Cat Comfortable

 

Treatment with Human Erythropoietin (rhEpo)

Epogen, Procrit and Eprex

Aranesp NeoRecormon
What is the Antibody Risk?

Why the Antibody Risk is Not as Bad as It Sounds

Why a Stop/Start Approach is a Bad Idea

Using Aranesp if a cat develops the antibody reaction to Epogen

 

Dosage and Usage Guidelines for Epogen, Procrit or Eprex

 Obtaining Epogen, Procrit or Eprex

 

 

Introduction

 

Anaemia is relatively common in CRF cats, so it is important to know about it and to be prepared to deal with it.

 

1.  What is Anaemia?

 

Anaemia is a condition in which not enough red blood cells exist in the body. Red blood cells transport oxygen round the body, so if a cat does not have enough, he/she will not be able to function properly and will feel very tired and weak; other symptoms are discussed below.  Red blood cells are produced in the bone marrow and last for around 70-80 days in cats. 

 

2.  Why Does Anaemia Occur in CRF Cats?

 

Healthy kidneys produce a hormone called erythropoietin, which stimulates the bone marrow to make the blood cells. As the kidneys fail in CRF, they cannot produce enough erythropoietin, so the bone marrow is not stimulated, blood cells are not produced, and a particular type of anaemia called non-regenerative anaemia results. In addition, a uraemic toxin called parathyroid hormone, which is not processed properly by damaged kidneys, may also adversely affect the production of erythropoietin. And finally the lifespan of red blood cells in renal failure patients is approximately 50% that of healthy cats.

 

How Stuff Works has a simple article about how blood cells are made. 

Understanding anaemia is an excerpt from a book by Ed Uthman.

 

3.  Major Symptoms and Risks of Anaemia

 

It is very important to treat anaemia because it can have some serious effects on the body: 

 

Faster Heart Rate

Haemoglobin is the main oxygen-carrying protein of red blood cells. Because haemoglobin is less concentrated in anaemia, the heart rate increases in an attempt to push the reduced amount of haemoglobin around the body. This faster heart rate is called tachycardia. Occasionally anaemia may cause a heart murmur.

 

High Blood Pressure

The heart tries to provide more blood, and thus oxygen, to the body's cells by increasing the pressure with which it pumps. 

 

Breathlessness

Because of the lack of haemoglobin, there is less oxygen in the body's tissues. The cat therefore breathes more often and more deeply, and may appear to be breathless.

 

Weakness

This is also caused by the lack of oxygen in the tissues, which means the cells cannot work as effectively.

 

Oedema and Heart Failure

The heart can only compensate for the lack of haemoglobin to a certain extent. Eventually, if the problem remains untreated, blood will build up and fluid will leak into body tissues. This causes swelling known as oedema. If oedema occurs in the lungs, it is known as pulmonary oedema and if it is left untreated this can kill the cat.

 

The University of North Carolina has some information on the risks of anaemia in connection with heart failure in humans.

Virginia-Maryland Regional College of Veterinary Medicine has examples of breath sounds, including the sound a cat with pulmonary oedema makes.

 

Other Symptoms

You may also see some milder symptoms such as pale eyelids, or eating litter - please see Index of Symptoms and Treatments and Symptoms for more information. 

 

As you can see, anaemia is potentially very serious - but fortunately it is also treatable.

 

4.  Other Causes of Anaemia

 

Before deciding on the best course of treatment, your vet must ensure that it really is non-regenerative anaemia caused by the CRF that you are dealing with. There are quite a few other causes of anaemia, including gastro-intestinal bleeding, particularly if the anaemia develops suddenly; most cats with anaemia caused by the CRF become anaemic gradually. A Vitamin B deficiency can also cause anaemia; whilst feeding onions to cats causes a specific type of anaemia called Heinz body anaemia, and it is possible that garlic (which belongs to the onion family) may also be a risk. In addition, cats with a hyperactive thyroid who are being treated with methimazole may sometimes develop anaemia.

 

Inflammation or infection may also cause anaemia. This may be because if a cat has an infection, the cat's body will sequester iron away (i.e. iron is stored rather than released into the bloodstream), because bacteria thrive on iron. Since iron is necessary for blood cell production, anaemia may result. Washington State University College of Veterinary Medicine mentions that pyelonephritis (a kidney infection) may cause non-regenerative anaemia in some cats, and this happens to my cat every time he gets a bout of pyelonephritis. Cats with Inflammatory Bowel Disease may also develop anaemia. 

 

Your vet can run tests to ascertain what sort of anaemia your cat has and whether it is regenerative or non-regenerative; but remember, there is a small chance of causing, or more likely, worsening anaemia if too much blood is taken from your cat for blood tests, so bloodtests should not be run too often on CRF cats. 

 

Feline anaemias: a diagnostic challenge is a paper on the various causes of anaemia presented to the World Small Animal Veterinary Association (WSAVA) 2002 Congress by Urs Giger.

Basic approach to anaemia diagnosis (2005) is a paper on the various causes of anaemia presented to the World Small Animal Veterinary Association (WSAVA) 2005 Congress by Harold Tvedten.

Murray State University has technical information on the diagnosis and classification of anaemia.

Merck Veterinary Manual discusses anaemia in a quite technical but useful manner.

Antech Diagnostics has an article entitled Canine Anaemia (which covers cats as well).

 

5.  How is Anaemia Diagnosed?

 

Packed Cell Volume (PCV) or Haematocrit (HCT)

Your vet will determine whether your cat has anaemia through a bloodtest called Packed Cell Volume (PCV), or occasionally a bloodtest called Haematocrit (HCT) which is very similar to PCV (see What Do All Those Test Results Mean?). PCV measures the ratio of red blood cells to total blood volume. It does not distinguish old blood cells from new but it is a still a useful and accurate test for anaemia. The blood is spun in a centrifugal machine and your vet measures what is left. Only a small amount of blood is needed for this test and many vets have the necessary equipment in their offices so you can get a result in a few minutes. 

 

Technically, a cat is anaemic if the PCV level is below 30% (or with some labs, 25%), but you may not start to see any differences in your cat's behaviour until the level is closer to 20%. Below 20% is generally considered to be severe anaemia, and it really must be treated as a matter of priority. Dehydration will make PCV look higher than it really is, so once the cat is rehydrated, PCV will often have fallen.

 

One person has been using a machine he purchased from Ebay to measure PCV at home in order to spare his cat the stress of vet visits and himself the cost of frequent tests. He found the machine he purchased was pretty accurate (varied by about 2% from vet readings). You can read more about this here. Personally, if I was dealing with severe anaemia (PCV below 20%), particularly if my cat was on Epogen, I would prefer regular vet visits in order to get accurate readings and to have my cat checked over by the vet.

 

Reticulocytes (Regenerative and Non-Regenerative Anaemia)

The PCV test shows if your cat is anaemic, but it does not show whether the anaemia is regenerative or non-regenerative. Regenerative anaemia means that the cat's body may be able to correct the anaemia without any external help, whereas with non-regenerative anaemia, the cat is going to need some help in the form of some kind of treatment.  Most (but not all) cats with CRF and anaemia are suffering from a type of non-regenerative anaemia caused by problems with erythropoietin production (see Why Does Anaemia Occur in CRF Cats?). 

 

The only way to know for certain which type of anaemia you are dealing with is by testing for reticulocytes; but this cannot be done unless the anaemia is already severe. 

 

Reticulocytes are immature red blood cells. Since anaemia means there is a lack of red blood cells, the body's usual response is to try to generate more red blood cells, so normally you would see reticulocytes if the anaemia is regenerative - this shows that the bone marrow is still making blood cells. However, in non-regenerative anaemia (as often seen in CRF), the lack of erythropoietin means the bone marrow is not able to make blood cells, or not enough of them to replace old ones, so there will be few or no reticulocytes present. 

 

The reticulocyte test is unlikely to be reliable unless the anaemia is moderate to severe - anaemia needs to be fairly bad before a brisk regenerative response is considered necessary by the cat's body - so many vets do not test for reticulocytes unless the PCV is below 20%. If the reticulocyte count is still low or zero despite the PCV being below 20% for five days or longer(at which stage of anaemia, the bone marrow would normally be busy making new red blood cells if it could), this indicates non-regenerative anaemia.

 

Since there is no point in measuring reticulocytes until PCV is below 20%, and since anaemia in a CRF cat is likely to be of the non-regenerative kind caused by the failing kidneys, many vets simply assume that a CRF cat with anaemia is suffering from non-regenerative anaemia and treat accordingly. This may not be a major concern for cats with PCV over 20%, when the standard treatments can be used and you have some time on your side while you try to bring the anaemia under control. However, for a cat with a PCV below 20%, where the anaemia is a more urgent problem and you need to act quickly, you will probably be considering the use of rhEpo (which only works for non-regenerative anaemia); and in view of the risks associated with this treatment, you might wish to have the reticulocyte test done to be sure you really are dealing with non-regenerative anaemia. Having said that, my vet felt it was more important that we start treating Thomas as quickly as possible, so we began rhEpo immediately rather than wait several days or more for the results of a reticulocyte test.

 

Cornell University College of Veterinary Medicine provides more information on this complex subject: click on the word Feline on the left of the page for further information, including a table of reticulocyte counts.

Antech Diagnostics have information on how they run this test.

Idexx Laboratories have some information on reticulocytes.

 

Mean Corpuscular Volume or Mean Cell Volume (MCV)

This is a measure of red blood cell size. If your cat has a low MCV, this may indicate a lack of iron (which can cause anaemia), or in some cases chronic liver disease. 

Cornell University College of Veterinary Medicine has more information about MCV.

 

Red Blood Cells (RBC)

If a cat cannot manufacture sufficient red blood cells, s/he will become anaemic. Unfortunately the lifespan of red blood cells in renal failure patients is approximately 50% that of healthy cats, so this is another reason why CRF cats become anaemic.

 

A low red blood cell count is usually indicative of anaemia. 

 

If the RBC count is high, this may be indicative of dehydration.

 

6.  Treatments

 

There are various treatments for anaemia, and which one you should use depends upon how severe the anaemia is. Your vet can advise you which is the most appropriate treatment, though you need to be aware that not all vets have used rhEpo (see below) or know much about it.

 

Iron

Haemoglobin, which as mentioned earlier is the main oxygen-carrying protein of red blood cells, needs iron for its production. Iron deficiency appears to be relatively common in CRF cats, so, in some cases, an iron supplement is all a cat needs to control anaemia. Iron supplements can be given orally or a monthly injection can be given, though the injection is into muscle so it can be painful. Generally speaking, all CRF cats with mild to moderate anaemia (PCV or HCT below 30%) would probably benefit from an iron and vitamin B supplement. 

 

All iron treatments may cause constipation or stomach upsets, so they should only be given if they are necessary. If a cat has an infection, the cat's body will sequester iron away (i.e. iron is stored rather than released into the bloodstream), because bacteria thrive on iron. This means the cat's body will be unable to use any iron you give, so it is better to get any infection under control before using iron.

 

Phosphorus binders should ideally be given separately from iron, because the binders may reduce the absorption of the iron. Drugstore has some information about this interaction.

 

Pet Education discusses iron requirements in cats.

Pet-tinic, apparently now also known as Pet Tabs Iron Plus, is both an iron supplement (containing iron proteinate) and Vitamin B supplement (see correcting vitamin deficiencies), and is very popular on the CRF Information List. The usual dose for a 10lb (4.5kg) cat is 1 ml twice a day (which equates to 5.4mg of iron a day), but do check with your vet in case your cat needs a different dose. 

KV Vet Supply will ship Pet Tabs Iron Plus to the UK. Click on Pet under Complete Catalogue, then click on Vitamins and Nutrition, then click on Supplements for Cats, and finally click on Blood Support for Cats; or just search for Pet tinic. It costs US$6.85 for 4 oz (February 2007), but shipping to UK is relatively expensive, at around US$27 (land) or US$39 (air). This company will also ship to Canada.

California Veterinary Supply sells something similar to Pet-tinic called NutriVed for $6.99 for 4 oz, which has the advantage of containing folic acid, which Pet-tinic lacks. It is also available from  Healthy Pets at a cost of US$9.99 for 4 oz.

Natural Pets also sell Nutrived for US$9.99 and will ship to the UK. Shipping via USPS Express Mail for one or two bottles costs around US29.

 

Fer-In-Sol is an infant iron supplement containing ferrous sulphate which may be suitable for some cats: the dosage for a 10lb (4.5kg) cat appears to be 0.1 ml (yes, 0.1ml, not 1ml) twice a day (which equates to 5mg of iron a day); but do check with your vet about dosage, since this is not a veterinary product. Please note this is only iron, so you may need to supplement B Vitamins separately.

 

UK

We used an iron supplement from Boots the Chemist called Sytron, which contained 27.5mg of iron per 5ml. Your vet can suggest an alternative brand and give advice on dosage.

 

If you are in the UK, you may be offered a newish product called Kaminox. This is a combination of B vitamins, iron and potassium.  Alfamedic provides a list of the ingredients. There is a similar product in the USA called Amino B & K, available from Emerson Ecologics. I would not recommend using such products unless your cat has low potassium levels, which not all CRF cats do; giving potassium when it is not needed can be very dangerous. Please also be aware that ACE inhibitors such as Fortekor may make potassium levels rise; so if your vet has prescribed Fortekor, as so many British vets do, it might be wiser to use a different type of iron without the potassium.

 

Vet UK sells Kaminox for £29.49 for 120ml, with free UK shipping.

Caledonian Cat Clinic sells Kaminox for £30.55 for 120ml.

Vetscriptions sells Kaminox for £30.99 for 120ml.

 

Spatone is an interesting possibility if you live in UK. This is a spa water which contains naturally occurring iron. The manufacturers claim that using iron in this way makes it more easily absorbed into the body. The manufacturers know of several dogs taking the product without problems, and one Feline CRF Information listmember is now using this product on her cat with her vet's approval.

 

Spatone is sold in sachets, and a box of 28 sachets costs £6.90, though discounts may be available for four boxes of 28 sachets or more. The product does taste of iron, so the manufacturers recommend giving the product in additional water. They suggest using 0.5-1.5 sachets per day in cats, which would be the equivalent of 100mg of ferrous sulphate.

 

Correcting Vitamin B Deficiencies 

A lack of certain B Vitamins, such as Vitamin B12 or Folic Acid (Vitamin B9), can cause non-regenerative anaemia. Your vet can prescribe a suitable supplement, or give your cat Vitamin B injections.  Generally speaking, all CRF cats with mild to moderate anaemia (PCV or HCT below 30%) would probably benefit from an iron and vitamin B supplement. 

 

Be careful about using multivitamin supplements because they may contain other vitamins such as A and D which are not usually suitable for CRF cats. I would also not recommend giving Vitamin B via additions to sub-Q fluid bags. Please see the Food Composition and Nutritional Requirements page for more information about vitamins.

 

Vitamin B12 may be particularly helpful. Vitamin B12 in the form of methylcobalamin (rather than the more commonly available cyanocobalamin) is the neurologically active form of Vitamin B12, and is used by the body to correct neurological problems. Apart from its role in preventing anaemia, it appears to help cats with diabetic neuropathy, and  has also been found by Feline CRF Information list members to be very helpful for various CRF-related problems, including incontinence and constipation. A possible starting dose would be 500mcg (0.5mg) a day, though some people give twice as much. Be guided by your vet. Methylcobalamin is often sold in the form of fruit-flavoured lozenges which some people do use to pill their cats successfully, though plain methylcobalamin tablets are also available, though less easy to find.

 

PDR Health has some information about methylcobalamin (this is a human site).

Vitacost sells 200 plain methylcobalamin 500mcg (0.5mg) capsules for US$11.99. I ordered these myself on a Sunday evening, and received them on the following Tuesday.

Bayho sells 180 1000mcg (1mg) plain methylcobalamin tablets for US$26.81. Although the site states that it only sells to health professionals, they will normally sell to individuals if you tell them it is for veterinary use.

Vitamin UK sells a number of different types of methylcobalamin, click on Search, then type in methylcobalamin.

Methylcobalamin Resources has details of suppliers in USA, UK, and New Zealand, some of whom will ship worldwide. Please note this site is recommending methylcobalamin for cats with diabetes, and the doses given may be too high for a CRF cat; ask your vet.

 

B Vitamins are sensitive to heat and light so are best kept in a cool dark place. Some vets add Vitamin B to the sub-Q fluids bag, but this is not a good idea because it can make the fluids sting; it can compromise the sterility of the bag; and giving vitamins in this way is very expensive. 

 

I would avoid using multi-vitamin products, particularly two products called Hi-Vites and Felovite II, as a source of B vitamins. These products tend to be too high in Vitamins A and D for a CRF cat, and Felovite II also contains phosphorus. Several cats on the CRF List have not done well on Hi-Vites in particular.

 

If you are in the UK, you may be offered a newish product called Kaminox. This is a combination of B vitamins, iron and potassium.  Alfamedic provides a list of the ingredients. I would not recommend using Kaminox unless your cat has low potassium levels, which not all CRF cats do; giving potassium when it is not needed can be very dangerous. Please also be aware that ACE inhibitors such as Fortekor may make potassium levels rise; so if your vet has prescribed Fortekor, as so many British vets do, it might be wiser to use a different type of B Vitamin without the potassium.

 

Vet UK sells Kaminox for £29.49 for 120ml, with free UK shipping.

Caledonian Cat Clinic sells Kaminox for £30.55 for 120ml.

Vetscriptions sells Kaminox for £30.99 for 120ml.

 

Provet in the UK sells a Vitamin B supplement that is phosphorus-free, which costs £8.32 for 30 tablets.

Pet-tinic, apparently now also known as Pet Tabs Iron Plus, is both an iron supplement and Vitamin B supplement. The usual dose for a 10lb (4.5kg) cat is 1 ml twice a day (which equates to 5.4mg of iron a day), but do check with your vet in case your cat needs a different dose. 

KV Vet Supply will ship Pet-tinic to the UK. Click on Pet under Complete Catalogue, then click on Vitamins and Nutrition, then click on Supplements for Cats, and finally click on Blood Support for Cats; or just search for Pet tinic. It costs US$6.85 for 4 oz, but shipping is relatively expensive.

California Veterinary Supply sells something similar to Pet-tinic called NutriVed for $6.99 for 4 oz, which has the advantage of containing folic acid, which Pet-tinic lacks. It is also available from Healthy Pets at a cost of US$9.99 for 4 oz.

Natural Pets also sell Nutrived for US$9.99 and will ship to the UK. Shipping via USPS Express Mail for one or two bottles costs around US29.

 

David Jacobson's Pages provide details on many Vitamin B supplements in the USA, which you may prefer to use instead of Pet-tinic if your cat does not need iron.

 

Anabolic Steroids

If anaemia is not too severe, anabolic steroids may help improve anaemia or at least slow down its progression. They may also be beneficial for CRF cats with muscle wasting and as an appetite stimulant. Your vet may prescribe anabolic steroids in the form of either tablets or injections. Commonly used anabolic steroids in Europe are Nandoral (Ethylestrenol in  tablet form) or Laurabolin (injectible Nandrolone). Winstrol-V (stanazole) was popular in the US but unfortunately, it appears to have been unavailable since September 2004, which apparently is related to some type of FDA regulation. It may still be obtainable from some compounding pharmacies.

 

Steroids may damage the liver so your vet will need to monitor your cat's liver values. 

 

There is more information about steroids on the Treatments page.

 

Erythropoietin

Another possible treatment for anaemia is erythropoietin, which is sold under the names of Epogen, Eprex or Procrit.  This is quite a complex subject, so it has its own section below.

 

Blood Transfusions

These are another possible treatment but again, this is quite a complex treatment so it is discussed in more detail below.

 

Human Erythropoietin

 

What is Human Erythropoietin?

Erythropoietin is the hormone made by healthy kidneys which stimulates the bone marrow to produce red blood cells. Since CRF cats can gradually lose the ability to make erythropoeitin, a synthetic version of human erythropoeitin known as Epoetin Alfa Recombinant or rhEpo may be used, which takes the place of the cat's natural erythropoietin and enables the bone marrow to continue to make red blood cells. Common trade names are Epogen, Procrit or Eprex.

 

The manufacturers of Epogen also make another type of human erythropoietin called Aranesp (darbepoetin alfa), and recently some people have been using this on their anaemic cats instead of Epogen, Procrit or Eprex. See below for more information.

 

Recently in Europe, some people are being offered another product called NeoRecormon. This is Epoetin Beta Recombinant.

 

Epogen, Eprex or Procrit

  • Epogen, made and sold by Amgen, is the name of the synthetic version of human erythropoietin (epoietin alfa) used in the USA for the treatment of anaemia in dialysis patients.

  • Procrit is the same product, epoietin alfa, made by Amgen but sold by Ortho Biotech in the USA for the treatment of anaemia in non-dialysis patients. It is also commonly used for cancer patients with anaemia caused by chemotherapy.

  • Eprex is the name of the version of epoietin alfa made by Centocor and sold by Ortho Biotech in Europe for the treatment of anaemia in both dialysis and non-dialysis patients. It is also used for patients with anaemia from other causes, such as chemotherapy. Whilst Eprex is also epoietin alfa, it is not identical to Epogen/Procrit.

Any of these products may be used for cats with severe CRF-related non-regenerative anaemia. In order to avoid confusion with the different trade names, the term rhEpo (recombinant human erythropoietin) will be used in this section. 

 

Antibody Risk

RhEpo is an extremely effective drug, but unfortunately, there is one major disadvantage to using it. RhEpo is a human version of erythropoietin, manufactured from human DNA. As a result, some cats will eventually produce an antibody reaction to the drug because their bodies consider it to be a foreign body. It is not known for certain how many cats go on to develop this antibody reaction because it is hard to test for this; but Dr Katherine James, a feline kidney specialist, took part in the 1998 clinical trials on the use of rhEpo in cats (Cowgill LD, James KM, Levy JK, Egrie JC, Browne JK, Miller A, Lobinger R: Use of recombinant human erythropoietin for management of anaemia in dogs and cats with renal failure Journal of the American Veterinary Medical Association 212 pp521-8), and in those trials the number of cats who developed the reaction was around 30%. However, on the Feline CRF Information and the Anaemia list, the frequency of the antibody reaction in practice appears to be far lower than 25-30%, perhaps closer to 5-10%. See below for a possible explanation of this discrepancy.

 

Whatever the actual percentage, as a result of this risk it is usually recommended that cats should not be placed on rhEpo until the benefits of using the rhEpo are thought to outweigh the risks - for most cats this means once their PCV has fallen to 15-19%. In theory, this will often not happen until the CRF is fairly well advanced with creatinine levels over 500 (US: 5.65), although this is not always the case - Thomas needed rhEpo regularly when his creatinine level was only 316 (US: 3.57).  

 

It is impossible to predict which cats will develop the antibody reaction, although a recent report from Janssen-Ortho, the manufacturers of Eprex, indicates that Eprex appears to carry a higher risk of the antibody reaction for humans than either Epogen or Procrit, particularly if the HSA-free form of Eprex (which contains polysorbate 80 instead of albumin, in order to comply with European requirements) is used. Erythropoietin-associated PRCA: still an unsolved mystery (2006) Schellekens H, Jiskoot W Journal of Immunotoxicology 3(3) pp123-130 reports further on this issue.

 

The reaction does not usually occur in the first month of use, and if it is going to occur it almost always happens around 4-5 months of commencing treatment (only rarely does it happen much earlier or later than this). There is no definitive test to show that the cat has developed the antibody reaction; a bone marrow aspiration would provide some information, but is invasive and unlikely to be worthwhile. Washington State University has some information on this procedure. 

 

From a practical perspective, the main sign of an antibody reaction is that the cat's PCV value will steadily drop by approximately 2-3% a week, despite the use of adequate amounts of rhEpo. Large drops in PCV in the space of a few days or a week are very unlikely to be caused by the antibody reaction, and other possible causes such as gastro-intestinal bleeding should be investigated. 

 

Note the use of the word "adequate": to complicate matters further, your cat may actually need more rhEpo than you have been giving: many vets give a too small dose in the mistaken belief that this may reduce the risk of the antibody reaction. Plus some cats simply need more Epogen than others - Thomas's PCV went up and down in the first few weeks of treatment so we were very worried, but we simply gave him more rhEpo rather than less, and his PCV then rose steadily. A cat whose CRF is advancing may also need more rhEpo than s/he previously needed. A cat who appears not to be responding to rhEpo may also need more iron. If for some reason you are using the 10,000 strength and above, be aware that the rhEpo may lose its potency before you get a chance to finish the vial. This can lead you to incorrectly suspect that your cat is developing the antibody reaction.

 

So if PCV levels do begin to fall, you should not automatically fear the worst, but instead should consider all other possible causes of the fall.

 

One other issue which I am asked about occasionally relates to a warning issued by the US Food & Drug Administration in 2007. This was in connection with using rhEpo in humans, and it recommends aiming for lower target haemoglobin levels than many doctors originally aimed for, because this reduces the risks of serious side effects. However, it has always been recommended that people aim for a conservative HCT level of no more than 35% in cats using these products, so I do not think this warning raises any additional concerns at this time. Incidentally, this paragraph does not contain typos:  targets are measured in haemoglobin for human rhEpo patients but in haematocrit or packed cell volume for cats.

 

Why the Antibody Risk is Not as Bad as it Sounds

Whilst nobody wants their cat to experience the antibody reaction, it must be stressed that it is not as awful as it sounds. Some people think it is akin to anaphylactic shock but it is nothing like that at all! All that happens is that the PCV gradually falls at a rate of 2-3% a week (any larger fall and you should search for another cause, such as gastro-intestinal bleeding), despite the cat being on rhEpo. If the cat is still producing a little erythropoietin naturally, the antibodies may also neutralise the cat's own erythropoietin as well, at least for a while, and this further worsens the anemia.  Since the resulting anaemia will eventually kill the cat, the only remedy is to stop using rhEpo. But the cat was already suffering from severe anaemia, otherwise rhEpo would not have been started in the first place. So in the worst case, using rhEpo will have bought you an extra few months with your cat; and in the best case, using rhEpo could control your cat's anaemia indefinitely. 

 

But, and most importantly, even in those cats who develop the antibody reaction, the rhEpo antibodies will not always neutralise the effects of the rhEpo. In other words, some cats may have the antibody reaction but you would never know it because the rhEpo continues to work and the cat does not become anaemic again. This may explain why it is often claimed that 30% of cats develop the antibody reaction, yet in practice on the Feline CRF and Anaemia Lists, the percentage appears to be much lower, around 5-10%.

 

This is not to minimise the stress of making the decision to use rhEpo. I know it is not easy.  However, since the alternative to starting rhEpo is to watch your cat die of anaemia, to some extent there is no real decision to make, particularly since if you wait too long before starting rhEpo, your cat may die of the anaemia before the rhEpo has a chance to take effect (it may take up to two weeks to see an improvement after starting to use rhEpo). We decided to use rhEpo because, firstly, it was quite obvious that if we did not do so, the anaemia would kill Thomas long before the CRF would (he was very weak); and secondly, we felt the odds were in our favour with at least a two to one chance that it would work for us. 

 

If you are considering the use of rhEpo, don't take too long to make your decision. Because non-regenerative anaemia caused by CRF tends to develop and worsen gradually many cats' bodies do adapt to the anaemia, so they may not seem desperately ill but could still be heading towards a crisis should the PCV fall too low. Plus once you begin rhEpo, it takes a couple of weeks to start taking effect, and even then the PCV should only increase by 2% a week, so if you wait too long your cat could die of anaemia before the rhEpo can help. In such cases a blood transfusion might tide your cat over through the critical period.

 

Personally I would never let PCV fall below 15% before starting rhEpo, and if my cat was showing symptoms of anaemia with a PCV of 16-20%, I would start it earlier.

 

So, to summarise:

  • at the present time there are no alternatives to Epogen, Procrit or Eprex for the treatment of severe CRF-related non-regenerative anaemia (milder anaemia may be treated via the methods outlined above).

  • if you do not use Epogen, Procrit or Eprex for severe CRF-related non-regenerative anaemia, your cat will die of anaemia.

  • the antibody reaction is rare. Even going by the worst case statistics, your cat has less than a 1 in 3 chance of developing the antibody reaction. Based on what I've seen over more than six years on the Feline CRF and Feline Anaemia lists, your cat has more like a 1 in 10 to 1 in 20 chance of developing the antibody reaction.

  • if your cat does develop the antibody reaction, it will not usually be for 4-5 months, during which time your cat will have no problems at all with anaemia.

  • if the antibody reaction occurs, your cat will gradually become anaemic again, which simply means you will be back where you started (4-5 months earlier) when you first decided to use Epogen, Procrit or Eprex.

  • if the antibody reaction occurs, you will see a fall in PCV/HCT of around 2% a week. A larger fall should lead you to suspect other causes, such as gastro-intestinal bleeding.

  • if your cat develops the antibody reaction, you will probably have to use blood transfusions to control the anaemia instead. At the present time I know of no other treatment, except possibly Aranesp, another type of human erythropoietin.

  • if your cat, as is most likely, does not develop the antibody reaction, s/he will have no problems with anaemia and all its attendant side effects in the future.

Ultimately it is your decision whether to use rhEpo. There have been trials into feline alternatives (see alternatives to human erythropoietin) but, according to the researchers involved, neither of these studies is expected to result in the commercial availability of alternative treatments in the foreseeable future. 

 

Why Stopping and Starting Epogen is a Bad Idea

Very occasionally, it is possible to stop giving rhEpo completely. In fact, if your cat has acute renal failure rather than CRF, you may not need to start it in the first place - although cats with ARF tend to have high bloodwork results generally, they often are not anaemic, or, if they are, the anaemia resolves itself naturally as the kidneys begin working again.

 

However, I have heard that some vets have a policy for every CRF cat they treat of using rhEpo short-term until the anaemia is resolved, then stopping it and starting it again later when the cat has become anaemic again, in the mistaken belief that this may reduce the risk of the antibody reaction.

 

This is really not a good idea. Dr Kathy, who participated in the Epogen trial in cats mentioned above (the trial that has many vets worried about the antibody reaction in the first place) has stated that there is no evidence either way, but she suspects that doing this might actually increase the risk of the antibody reaction occurring. She also believes that the resulting fluctuations in PCV could cause problems with blood pressure control.

 

On the most basic level, I really do not see the point of allowing a cat to become anaemic again, with all the strains on the body and effects on the cat's quality of life which that entails. In addition, I heard from one person whose vet insisted on this approach and whose cat died from anaemia during one of his anaemic phases. If you decide to use rhEpo, I'd recommend making a commitment to using it fully in order to keep your cat completely free of anaemia.

 

Dosage and Usage Guidelines for Epogen, Procrit or Eprex

 

I suggest you read this entire section in order to familiarise yourself with how to give rhEpo. Topics covered include:

Obtaining rhEpo

RhEpo is available in various strengths but you do not want the 10,000iu and higher strengths, because it is too hard to obtain cat-sized doses from these. In the USA the strengths most commonly used for cats are 2,000iu and 3,000iu, but in the UK and Canada you may be offered the 1,000iu strength, which confusingly is the same as the 2,000iu strength, but half the amount. Obviously, if you are using a lower strength, you need to give more of it. Your vet should be able to advise you on which strength to buy. Click on the country you are interested in:

UK

In the UK, if your vet doesn't have it in stock, rhEpo (trade name Eprex) is available from pharmacies, although you will need a prescription from your vet, and the pharmacy may have to order it in for you (usually it can be delivered in a day or two). It costs around £90 for six 1000iu syringes, which is the equivalent of 12-24 treatments for most cats. One lady wrote to tell me that she was able to obtain Eprex very quickly from her local hospital pharmacy, with a prescription from her vet, of course.

 

Since we used Eprex in pre-filled syringes, we simply used the syringe and needle in which the Eprex came, giving half the vial each time.

 

USA

In the USA, it is often possible to obtain the US version of rhEpo, Epogen, by mail order (with a prescription), although you have to be very careful about it being refrigerated during shipping. 

 

Some of the pharmacies below offer family savings plans whereby you pay an annual membership fee and then receive a discount on the price of your prescription medications. These schemes often permit cats to be enrolled as family members, which may further reduce your costs.

  • Walmart Specialty Pharmacy sells Epogen, apparently for around US$28 per 2,000iu vial, with free shipping. The website does not currently show prices so this is the approximate price. However, it can take around a week to complete the registration process the first time you order. Wal-Mart will contact you to ask for your preferred delivery date, so you can be sure you are there to receive it.

  • Walgreens sells one vial of the 2,000iu strength for around US$36.99, or three vials for US$98.89 (works out at US$32.96 a vial). The website does not currently show prices so this is the approximate price. Walgreens also sells six of the 2,000iu strength of Procrit (same drug as Epogen) for US$197.99 (February 2007), but this works out at US$33 a vial, so buying six vials of Epogen at a total of US$197.78 would just work out cheaper.

  • Family Meds sells ten vials of the 2,000iu strength of Epogen for US$233.87, which works out at US$23.39 a vial, but ten vials are a lot to buy at one time. Family Meds also sells six vials of the 2,000iu strength of Procrit (same drug as Epogen) for US$171.87, which works out at US$28.65 a vial.

  • Drugstore sells Epogen for US$36.35 per 2,000iu vial but there is also a US$17 overnight delivery charge, so you might prefer to order several vials at one time.

If you don't want to order online, some local pharmacies in the USA, such as Walgreens, can order Epogen with overnight delivery for around US$30-35 per 2,000iu vial. Hospital pharmacies often have Epogen in stock and may well be prepared to sell it to you with a prescription.

 

You will probably also need U100 insulin 0.3 or O.5cc syringes, which cost around US$15 per hundred (Brico Medical sells 100 Terumo syringes for around this price though you will need a prescription). You can also obtain insulin syringes from your local pharmacy. Since we used Eprex, we did not need insulin syringes, instead we used the syringe and needle in which the Eprex came, giving half the vial each time. The Obtaining Supplies Cheaply page also has information about obtaining supplies cheaply, including links. 

 

Canada

I am not aware of any suppliers in Canada, though Eprex is certainly used there, and should be available from local pharmacies, particularly hospital pharmacies. If you cannot find a Canadian supplier, Entirely Pets in the USA sells Epogen for US$45.99 for a vial of the 2000iu strength and will apparently ship to Canada.

 

Commonly Used Dosages

You should check with your vet on the appropriate dosage for your cat. For reference, The Veterinary Drug Handbook (4th edition) (2002) by Donald C Plumb suggests using 100 units of rhEpo per kg (2.2lbs) of cat, given sub-cutaneously three times a week until you begin to approach the target PCV level (usually around 35%). 

 

Some cats may require higher doses initially, particularly cats with severe anaemia. Plumb's suggests using up to 145 units per kg (2.2lbs) of cat, also given sub-cutaneously three times a week, if anaemia is severe (PCV or HCT below 14%). Even if your cat does not have severe anaemia, discuss this possibility with your vet if your cat does not appear to respond to the treatment.

 

However, a lower dose of 48.4 units per kg (2.2lbs) of cat, sub-cutaneously three times a week, may be advisable if the cat has hypertension (high blood pressure) before starting rhEpo.

 

Calculating Your Cat's Dosage

 

The exact amount of rhEpo to be given depends upon the strength which you are using. RhEpo is sold in varying strengths, but the larger sizes (10,000iu/mL upwards) are impossible to give in cat-sized amounts, so try to use nothing larger than the 3000iu/mL strength. If for some reason you do end up using the 10,000 strength and above, be aware that the rhEpo may lose its potency before you get a chance to finish the vial. This can lead you to incorrectly suspect that your cat is developing the antibody reaction.

 

Calculating how much rhEpo to use can be very confusing! Normally you will be told how many units to give, based on your cat's weight. 1 cc of the 3000iu/mL strength contains 3000 units of rhEpo; 1 cc of the 2000iu/mL strength contains 2000 units of rhEpo; and so on. We used the 1000iu strength, which (just to confuse matters) is slightly different: it contains 1000iu but in 0.5mL so it is the same strength as the 2000iu/mL although it sounds different. Whichever you use is less important than giving the correct amount of rhEpo.

 

If you are using Epogen or Procrit, you will probably also need U100 insulin 0.3 or O.5cc syringes (see above for sources). To complicate matters even further, insulin units are not the same as Epogen units. However, 1 insulin unit is 0.01cc; so each unit on an insulin syringe is 0.01cc, which should help you when you come to measure out the dose. I would still recommend asking your vet to show you exactly how much to draw up though.

 

As you can see, the dosages below are pretty precise, but your vet will probably want to round the dose up or down so as to make it easier for you to measure it.

 

 

If Dosage of 100 units per kg in Weight is Prescribed

  8 lb (3.65kg) Cat 10 lb (4.5kg) Cat 12 lb (5.45kg) Cat

Epogen Strength

Needs

365 Units

Needs

450 Units

Needs

545 Units

1000 iu/mL 0.1835 cc 0.225 cc 0.273 cc
2000 iu/mL 0.1835 cc 0.225 cc 0.273 cc
3000 iu/mL 0.122 cc 0.15 cc 0.18 cc
4000 iu/mL 0.09 cc 0.1125 cc 0.137 cc

 

During the first few weeks of using rhEpo, PCV levels should be monitored carefully. Whilst low PCV levels are dangerous, too high levels (polycythaemia) increase the chances of thrombosis and associated heart problems, so the usual PCV to aim for is around 35%.

 

It takes 70-80 days for blood cells to develop so this should be borne in mind when calculating amount and frequency of dosage because PCV levels will still be rising for some time after each dose.

 

It usually takes around 1-2 weeks for rhEpo to show an effect, with PCV rising a couple of percentage points a week. Your vet should check PCV a week after starting rhEpo, and again a week later. If PCV is rising faster than 4% in two weeks, you should ask your vet about reducing the amount given, because rises in excess of this level have been associated with an increased risk of hypertension in human patients. The Epogen Website mentions this (see page 10).

 

Once the PCV level is close to your goal of 35% (i.e. in the low 30s), the dose frequency is reduced to whatever level is necessary to maintain the PCV at the desired level. Many vets reduce dosing frequency to twice a week initially, but may then reduce to once a week or eventually to only once every 10-14 days. You may also be able to reduce the amount of rhEpo given to as low as 75 units per kg bodyweight. Very occasionally, it is possible to stop giving rhEpo completely. Naturally, if the anaemia begins to recur, you will need to increase the amount and/or frequency of the rhEpo injections. There is a timelag of approximately two weeks between giving rhEpo and seeing its effects on PCV, so you need to bear this in mind when adjusting dosages.

 

Once a cat has reached a stable PCV in the mid 30s on rhEpo and is no longer anaemic, I would recommend still checking PCV every six weeks or so in order to ensure that your cat is not developing the antibody reaction.

 

How to Give rhEpo

RhEpo is administered by way of sub-cutaneous injection, so most people give it to their cat themselves at home. It may sting, although Thomas did not react too badly to it. You will still have to visit the vet at regular intervals initially, in order to monitor PCV or HCT levels and blood pressure; but once the cat is on a maintenance dose, less frequent checks are required.

 

RhEpo contains no preservatives, so MUST be kept in the refrigerator in between treatments. It is fine to leave it out at room temperature for 20-30 minutes before administering it so it is not too cold when you inject your cat.

 

You should not shake rhEpo, though it is acceptable to roll it gently in your hand to warm it a little before giving it to your cat.

 

Some pharmacists tell people they can only use a vial once and then must throw it away; whilst this is true of human patients, it is standard to re-use vials for cats, and I am not aware of any problems arising from doing so (as long as the vial is not past its "use by" date, of course).

 

When you start giving rhEpo, the cat's body will try to produce a lot of red blood cells, but it needs sufficient quantities of iron in order to complete the process. It is therefore well worth using an iron supplement as well as rhEpo in order to ensure that your cat has all the necessary building blocks in place to enable the rhEpo to do its work. However, iron can be constipating, plus you may not need to give as much iron as you would give if you were trying to correct a fullblown iron deficiency, so some people find simply feeding a little liver (one or two tablespoons) once or twice a week provides sufficient iron with less risk of constipation. Most cats seem to like liver, though you should not give liver too often or in large quantities because it contains very high levels of Vitamin A. 

 

Monitoring

Blood pressure should be monitored while your cat is on rhEpo, particularly when you first begin treatment. Ideally you should have started monitoring blood pressure anyway, as soon as your cat was diagnosed with CRF; but if you have not been doing this, do try to ensure that blood pressure is monitored once you begin rhEpo, because it may increase blood pressure. Newman Veterinary briefly discusses this (click on Erythropoietin and Hypertension). 

 

See above for information on monitoring requirements when you first start rhEpo. Once a cat has reached a stable PCV in the mid 30s on rhEpo and is no longer anaemic, I would recommend still checking PCV every six weeks or so in order to ensure that your cat is not developing the antibody reaction.

 

When testing PCV, it is not necessary to draw a lot of blood (which could worsen the anaemia) - a tiny drop taken from the ear may be sufficient (Veterinary Partner has a description of how this is done in diabetic cats, as does Sugar Cats), so ask your vet if this method could be used, though some machines do need more blood than this.

 

Please note that dehydration inflates the PCV value. If your cat is dehydrated when PCV is tested, the value will be shown as higher than it actually is. In other words, if your cat has a just about acceptable PCV level, but is dehydrated when the test is run, your cat is in reality anaemic.

 

There is some debate as to whether ACE inhibitors may exacerbate anaemia and/or induce some resistance to the use of human erythropoietin (Epogen, Procrit or Eprex) in humans. The role of ACE inhibitors and angiotensin II receptor blockers in the response to epoetin (1999) MacDougall IC Nephrology Dialysis Transplantion 14 (8) pp1836-1841 reports on the evidence for and against this concern in humans. If your cat is on both rhEpo and an ACE inhibitor, I would discuss this with your vet.

 

NeoRecormon

Hoffmann LaRoche make a form of erythropoietin called NeoRecormon. This is epoetin beta, rather than epoetin alfa (Epogen, Eprex or Procrit). It is becoming more common to use NeoRecormon in Europe for cats with non-regenerative anaemia caused by CRF.

 

I have only heard from a few people using NeoRecormon, though Ollie will go on it if his anaemia worsens, at which time I will gain personal experience with it. Most people seem to be using it in similar fashion to Epogen or Eprex, giving it three times a week  and 50-100iu per kg of body weight (usually 100iu per kg of bodyweight is used for Epogen or Eprex). I did find one reference about using it, Veterinary Pharmacology, which suggests the above dose but which also recommends that PCV should increase by 1% a day for the first month (!), which seems inappropriate to me - I would recommend the more usual increase of 2% a week would be a more suitable goal.

 

Aranesp

Amgen, the manufacturers of Epogen, also make another type of human erythropoietin called Aranesp (darbepoetin alfa). There are two formulations of Aranesp, one containing human albumin, and one with no albumin known as HSA-free. Janssen-Ortho, the manufacturers of Eprex (the European version of Epogen), mention that the HSA-free form of Eprex, which contains polysorbate 80 instead of albumin in order to comply with European requirements, had a higher antibody reaction rate. Erythropoietin-associated PRCA: still an unsolved mystery (2006) Schellekens H, Jiskoot W Journal of Immunotoxicology 3(3) pp123-130 reports further on this issue.

 

I do not know if this is also likely to be true for Aranesp but it is a possibility. I would therefore suggest that you try to obtain the form of Aranesp containing albumin rather than the one without albumin (the polysorbate version).

 

Unlike Epogen, there have been no clinical trials of Aranesp involving cats. However, in 2005 a number of US veterinary schools began using Aranesp on an informal basis, including North Carolina State University, University of Penn, Animal Medical Center in New York, University of California at Davis, and the University of California Veterinary Medical Center (UCVMC). These latter four institutions hope to publish the results of their experiences in the next few years.

 

To date (January 2008) Aranesp has been used on approximately 50-60 cats at UCVMC, with favourable results. As a result, UCVMC now tends to use Aranesp as a first line treatment for most cats (except when they expect the need for rhEpo to be short-lived because the cat is an acute case, in which case they may use Epogen instead since it may show a quicker response time).

 

Aranesp is more expensive than Epogen - it comes in a 25mcg vial which costs around US$125-140 and which contains approximately four doses. However, since it does not need to be administered as frequently as Epogen, the cost should be the same overall. Unfortunately, most online retailers seem to sell a minimum of four vials, which costs over US$500. However, I have heard that CVS and Safeway may be prepared to sell one vial for around US$160 - 180.

 

RX USA sells four vials of Aranesp for US$509.08 or one vial for US$131.90 (you need the 25mcg strength). One person who used this company has apparently had problems obtaining a refund after the Aranesp was shipped incorrectly.

Drugstore sells four vials of 25mcg Aranesp for US$516.06 as at January 2008. I have used Drugstore myself for other items and have always received excellent service. 

Darbepoetin alfa: a new therapy for the management of anaemia associated with chronic kidney disease (2002) Lindberg J Expert Opinion on Biological Therapy 2(8) pp977-84 discusses the use of darbepoetin alfa in human patients.

 

Dosage and Usage Guidelines for Aranesp (darbopoietin alfa)

Many of the basic Epogen usage guidelines such as keeping the medication in the fridge, also apply to Aranesp, so please read them.

 

Dosage, however, is different. There are no established dosing paramenters, but generally speaking, Aranesp is given less frequently than Epogen, usually only once a week to start with. The dose for human patients on Aranesp is 0.45mcg per kg (a kg is 2.2 lb) body weight. This would mean that a 4.5kg (10 lb) cat would receive a dose of just over 2mcg. However, I have heard that the current dosage being used by some US veterinary schools is to give a single dose sub-cutaneously of 6.25 mcg each week, regardless of the cat's weight. One vet school gives 6.25 mcg along with iron in the first week, but then spaces it out as far as possible, usually giving it once every 2-4 weeks. I have also heard from a couple of people who gave their cats 5 mcg sub-cutaneously each week. One of these cats had a PCV that was increasing rather quickly though, despite being on a lower dose, so presumably caution must be exercised with smaller cats. When calculating your cat's Aranesp dosage, you must be guided by your vet. If your cat's PCV rises too quickly (more than a 2% increase in PCV or HCT per week), ask your vet about reducing the dose or giving the Aranesp less frequently, because it is important to adapt the dosing schedule to what works for your cat.

 

Because Aranesp is given less frequently than rhEpo, it also takes longer to take effect. Therefore, if your cat has very severe anaemia before starting Aranesp, you may need to consider a blood transfusion to tide your cat over until the Aranesp begins to take effect. 

 

As with Epogen, PCV should be monitored, ideally before administering the next dose, because you only want PCV to rise by around 2-3% a week (if it rises faster, it increases the risk of hypertension).

 

Also as with Epogen, you need to reduce the dosage of Aranesp as you approach target PCV of around 35% (i.e. when PCV is in the low 30s). In fact, I am told that it is usual to continue to use the same amount of Aranesp but to reduce the frequency - apparently many cats only need a maintenance dose every 3-4 weeks. 

 

It appears that Aranesp may be less likely to cause the antibody reaction sometimes seen with Epogen (although the antibody reaction is still possible with Aranesp). There has been one suspected case of the antibody reaction in a dog but this was never confirmed. There have been none thus far (January 2008) in cats, though it must be remembered that not many cats have been given this treatment as yet.

 

Using Aranesp in Cats Who Have Developed the Antibody Reaction to Epogen

It is not generally recommended to use any form of human erythropoietin in a patient who has reacted to another form (in other words, if you have developed the antibody reaction to Epogen, it is not advisable to use Aranesp instead). However, since there are some differences between Epogen and Aranesp, apparently some US vet schools are trying to maintain cats who have developed the antibody reaction to Epogen or Eprex by using blood transfusions for several (6-8) weeks, and then starting them on Aranesp, in the hope that the cats will not also develop an antibody reaction to Aranesp. Apparently there is anecdotal evidence that this approach worked for one cat but it did not work for any others. Sometimes prednisone, a steroid, is used in the interim period before starting treatment with Aranesp.

 

One person whose cat may have developed the antibody reaction to Epogen (this person's vet had recommended a stop/start approach, which is not recommended because it may increase the risk of the antibody reaction) tried to switch to Aranesp. He found that using Aranesp alone or Aranesp and prednisone did not help his cat, but using it in conjunction with both prednisone and chlorambucil (Leukeran), an immunosuppressive drug commonly used in the treatment of cancer, did help for a while. This regimen was based on the successful treatment plan for a woman who also developed the antibody reaction.

 

Successful reintroduction of a different erythropoiesis stimulating agent after pure red blood cell aplasia: relapse after successful therapy with prednisone (2005) Andrade J, Taylor PA, Love JM, Levin A Nephrology Dialysis Transplantation  20 pp2548-51 discusses the case of a woman who developed the antibody reaction and who was helped by prednisone.

Erythropoietin, cure or nightmare Chan SK, Chan CK, Chow CC (2004) is a presentation to the Hong Kong Society of Nephrology Interhospital Meeting about a woman who developed the antibody reaction and who was helped by prednisone and chlorambucil.

Mar Vista Vet has some information about chlorambucil (Leukeran).

 

8.  Alternatives to Human Erythropoietin

 

Because of the risks to cats of using rhEpo, there have been two recent studies in the USA looking at alternatives. i.e.

Sadly, although the trials appear to have gone relatively well, for various reasons it appears unlikely that they will eventually lead to the commercial availability of these  alternative treatments without the antibody risk.  

 

Feline Erythropoietin

 

A new synthetic form of feline erythropoietin (rfEPO) has been developed at Cornell University in the USA, and a one year trial for CRF cats was completed there in November 2002. The results of the trial were published in November 2004.

 

There were three parts to the clinical trial:

  • anaemia of CRF  - trial lasted 52 weeks;

  • red blood cell aplaesia induced by recombinant human erythropoietin i.e. for cats who had experienced the antibody reaction to rhEpo (human erythropoietin) - trial lasted 24 weeks; and

  • anaemia of lymphosarcoma, a form of cancer - trial lasted 24 weeks and was not completed due to lack of sufficient participants to provide statistically significant data.

The basic criteria for entry into the trials related to CRF and the antibody reaction were as follows:

  • your cat had to be more than one year old;

  • your cat had to have CRF, as diagnosed by your vet;

  • your cat had to have non-regenerative anaemia with a PCV under 20%;

  • your cat had to have no evidence of iron deficiency anaemia;

  • your cat's blood pressure had to be no higher than 180mm Hg;

  • your vet had to apply for inclusion in the trials, so you needed a vet who was prepared to work with you and Cornell;

Participants were not required to attend at Cornell, but their vet needed to liaise with Cornell. For the basic CRF trials, weekly bloodwork was required in the first eight weeks, reducing thereafter to every four weeks. The feline erythropoietin was provided at no cost and now the trials are over, Cornell is providing feline erythropoietin free of charge to former trial participants who still require rfEpo.  

 

Expression, bioactivity and clinical assessment of recombinant feline erythropoietin (2004) Randolph JF, Scarlett JM, Stokol T, Saunders KM and McLeod JN American Journal of Veterinary Research 65 (10) pp 1311-1450 explains the outcome of the study. Unfortunately, whilst the rfEpo was effective at curing anaemia in the study cats, even in those cats who had previously had an antibody reaction to rhEpo, 26% of the cats receiving rfEpo (and who had never used rhEpo) developed an antibody reaction to the feline erythropoietin.

 

Since rfEpo is currently unavailable commercially in any event, if your cat has severe (HCT or PCV below 20%) non-regenerative anaemia caused by CRF, I would suggest you seriously consider using rhEpo. After all, the alternative is death from anaemia.

 

Vetcentric has an article about the feline erythropoietin trials.

 

Feline Erythropoietin Gene Study

 

This study at Ohio State University investigated the development of a feline erythropoietin gene. The gene that makes feline erythropoietin is implanted into the leg or back muscle by an intramuscular injection similar to a vaccination. Tests conducted on healthy cats showed that this increased PCV levels over a seven week period following the injection.  

 

The original criteria for inclusion in the trials were:

  • your cat had to have CRF, as diagnosed by a vet;

  • your cat must never have used rhEpo (human erythropoietin, such a Epogen);

  • your cat must never have had a blood transfusion;

  • your cat must have a PCV of less than 27%; and

  • you had to be able to take your cat to Ohio State University approximately once every 1-2 weeks to start with, reducing to once a month, for a total period of one year. 

All medical expenses relating to the treatment were paid for.

 

Results to date have been mixed with some cats responding extremely well and others less well, but overall the trials are encouraging. Once the gene is implanted, the cat should produce erythropoietin on its own, and in the trials responsive cats have been doing so for up to one year. Further trials may be conducted in due course.

 

Transfer of the feline erythropoietin gene to cats using a recombinant adeno-associated virus vector (2000) Beall CJ, Phipps AJ, Mathes LE, Stromberg P, Johnson PR Gene Therapy 7 (6) pp 534-539 describes the beginning of the trial.

Prevention Magazine has brief information on the trial - scroll down to the section entitled "New hope for old cats".


9.  Blood Transfusions

 

This section covers the following:

Feline Blood Groups

Cats can receive blood transfusions just like humans. Cats have fewer known blood groups than humans, namely A (the most common, particularly in non-pedigrees), B (relatively common in pedigree cats) and AB (rare). However, unlike humans, cats do not have a universal donor (in humans, if blood type is not yet known, the person can be given the universal blood type, O negative, to tide them over with no adverse effects), although type AB cats can receive blood from either type A or B donors. In an emergency case such as a cat who is going to die anyway without the transfusion (e.g. after a traffic accident), a vet may do a transfusion without checking the blood types, and in the case of the average cat, this will often not result in disaster the first time it is done, though it is far riskier for pedigree cats who tend to have different blood groups.  However, if time permits (as it usually does for CRF cats), it is far safer to type or cross-match a  cat's blood type before a transfusion. 

 

A blood transfusion is not a major procedure, and normally the cat only needs to stay at the vet's for 3-4 hours; just long enough to receive the blood (which is given slowly) and to be monitored for a possible reaction. Most cats feel and act much better after a transfusion, and with a well-matched donor (see below), the effects may last for 4-5 weeks.

 

Whole blood transfusions in 91 cats: a clinical evaluation (2004) Weingart C, Giger U, Kohn B Journal of Feline Medicine and Surgery 6 (3) pp139-148 concludes that "with proper donor selection and appropriate compatibility screening, blood transfusions are well tolerated, appear effective, and may increase chances of survival."

Feline blood typing and transfusion - a practical approach (2006) Kohn B & Weingart C Presentation to the 31st World Small Animal Veterinary Association World Congress has a good overview of blood transfusions.

University of Illinois has general information about blood transfusions.

Cornell University College of Veterinary Medicine has information on feline blood groups and transfusions generally: use the links at top left.

Feline Advisory Bureau has a table showing the frequency of the different blood groups in various breeds.

Feline anaemias - therapeutic options and transfusion therapy is a paper presented to the World Small Animal Veterinary Association (WSAVA) 2002 Congress by Urs Giger.

 

Typing and Cross-matching

Typing means that you find a cat with the same blood group as your cat, and give blood from that cat. For example, if your cat has type B blood, then you find another cat with type B blood to act as the donor. Cross-matching means that further tests are done to check whether the typed donor cat's blood is compatible with the recipient's blood. This is important because there are further factors within cats' blood, so even if typing has been done, there is still a risk of a reaction if the blood has not been cross-matched, which in severe cases may cause shock and even death. Please note that even if a donor cat's blood has been successfully cross-matched once, it is safest to cross-match it again before using that cat as a donor once again, because the recipient cat may have built up antibodies to the donor cat's blood. 

 

Colorado State University Diagnostic Laboratory will type feline blood in the USA for US$35, and cross-match it for local clients for US$32 (click on Test Schedule, then on Clinical Pathology), though your vet may know of a local laboratory which can do this. If you cross-match, you do not need to type the blood as well, that will be done as part of the cross-matching.

NationWide Laboratories (UK) has an interesting article about feline blood typing, and can type blood for you for £28 (November 2002) with results available the same day.

The University of Bristol (click on Haematology on the left) offers feline blood typing for £21 and cross matching for £25, with both tests being turned around on the day of receipt.

 

Obtaining Blood

In addition to typing and cross-matching blood, the main problem with blood transfusions tends to be finding a donor cat at all, particularly at short notice. You may be able to use another cat in your family as the donor, or your vet may be able to find a cat (many vets occasionally offer their own cats as donors). 

 

When choosing a donor, naturally you want one who has been tested and found to be free of infectious diseases such as feline leukaemia. The donor also has to be healthy and big enough to give blood without any adverse effects for himself/herself - usually a donor must be at least 9-10 lb in weight. In addition, a donor usually cannot give blood more often than every two months. If the donor cat meets these criteria, there are no side effects for him/her, and it does not appear to be any more stressful than a standard vet visit for either the donor or the recipient.

 

Alternatively, in the USA, there are a limited number of feline blood banks which may be able to help, including: 

Midwest Animal Blood Services stocks feline blood.

Animal Blood Bank also stocks feline blood.

The Canadian Animal Blood Bank does not stock feline blood, but will provide advice and certain supplies on obtaining blood safely. The US blood banks mentioned above may be able to ship feline blood to Canada if required.

 

Oxyglobin (Synthetic Blood)

Oxyglobin is a synthetic blood product containing haemoglobin, which is approved for use in dogs as a single treatment only. It does not contain red blood cells, so its effects are short-lived (a couple of days). Since it is designed for dogs rather than cats, there is a risk of volume overload when using Oxyglobin (only 4% of a cat's body weight is accounted for by blood volume, whereas in dogs the level is 7%). It is therefore better to use normal blood for a transfusion, but in case of urgent need, a one-off use of oxyglobin might help buy you some time while you search for a suitable blood donor.

Biopure Corporation - the maufacturer's website.

Vetcentric has some information on the use of Oxyglobin.

 

Antibody Formation

Unfortunately, as with rhEpo, a cat may eventually develop a reaction to blood transfusions, and the odds seem to increase with each transfusion. The limit according to experiences on the Feline CRF Information list seems to be roughly five transfusions per cat. At the beginning, each transfusion lasts around five weeks, but this time tends to reduce with each transfusion until eventually a transfusion may only buy the cat a few days. 

 

If your cat develops a reaction to rhEpo, this does not increase the chances of your cat developing a reaction to donated blood. As a result, if your cat is severely anaemic, you might want to consider rhEpo instead of transfusions, and keep transfusions in reserve in case your cat does develop a reaction to rhEpo, at which time you could probably buy your cat some more time by using transfusions.  

 

10.  Making your Cat Comfortable

 

Minimising Effort

It is a real effort for anaemic cats to do simple things like jumping onto beds or climbing stairs; Thomas did not use the stairs for three weeks and simply stayed upstairs until he became stronger. It is a kindness to your cat if you can minimise the effort required to do simple tasks like visiting the litter tray. If you have a litter tray downstairs but your cat prefers to stay upstairs, place an extra litter tray upstairs not too far from your cat's favourite spot (but away from food and water). If the litter tray has a high edge which is hard for your cat to climb over, you may need to provide a litter tray with a lower edge until your cat has regained some strength.  

 

Similarly, provide food and water near to your cat's favourite place - he or she will be more inclined to eat if it doesn't involve an epic trek to the food bowl. 

 

Also try to reduce the amount of climbing your cat has to do: Thomas decided his favourite place was the bed, so we arranged a series of footstools, piano stools and so on in order to create a kind of stairway up to the bed.  We also placed Thomas's food bowls on the bed and his water bowl on the bedside table so he only had to get down in order to use the litter tray. But do be aware that occasionally a cat may no longer jump and climb because of blindness caused by hypertension.

Pet Planet in the UK sells a small folding ramp for £49.99.

House of Bath in the UK sells standard ramps for £59.95; search for "ramp".

Drs Foster and Smith sell a number of ramps and steps.

 

Heat Pad

Anaemic cats feel very cold, even in summer. The best treatment we could find, apart from treating the anaemia of course, was a heat pad. This is a small flat heated pad with a fleecy cover - it looks like a little flat cat-sized bed. Thomas had long legs but we found the 12 inches square bed was fine for him because anaemic cats tend to hunch up because they are cold.

 

Heat pads are designed for people with arthritis and such like but are excellent as electric blankets for anaemic cats because you just plug the heat pad into the mains, choose from three temperatures and then the pad stays at the chosen temperature constantly, unlike a hot water bottle. You must of course keep an eye on your cat while he or she is using this since it is electrical equipment, but certainly we never had any problems with overheating and Thomas found it very comforting when his anaemia was bad. 

Drs Foster and Smith sell a number of heated beds in the USA.

Boots the Chemist in UK sells a heatpad for £21.99 - this is the one we used for Thomas when he had anaemia.

Support List

Feline Anaemia is a list for people with anaemic cats, where you can obtain advice and support on treating anaemia. Unfortunately in recent times the list is not particularly active and some people go unanswered.

 

 

Harpsie doing his bit to keep Thomas warm when he had anaemia.

 

 

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This page last updated: 14 May 2009

 

Links on this page last checked: 19 January 2008

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