Feline Blood and Lymph Conditions and Disorders
Hypercalcemia in cats and elevation in the alanine transferase (ALT)
Question: Dear Dr. Richards:
First of all, GREAT website and newsletter! I've earned a lot from you over the years.
Since 1997, my husband and I have had one cat with intestinal lymphoma and two with congestive heart failure, all deceased. In each case, I felt that, had we been more proactive about pursuing early symptoms, all would have enjoyed longer lives than they did. We recently adopted a family of feral cats bringing our fur ball family to a grand total of 12, and, with the exception of 2 who have some lung scarring caused by a warehouse fire, all appear to be very healthy and active. All have tested negative for leukemia and AIDS and all got their requisite vaccinations.
On several occasions, however, we noticed that someone had urinated outside of the litter boxes. We had assumed it was probably a territorial issue, (all have been neutered and spayed but we ARE talking about 12 cats), but as Katie had been observed in the area of the last incident and she was scheduled for her yearly checkup, we decided to have a precautionary blood test done.
Katie is 3-4 years old and her calcium level was 13 mg/dl and ALT was 142 U/L. Although I know these aren't as high as they can get in cancer-diagnosed felines, my first thought on hearing this was that we might be dealing with lymphoma again. My vet is going to do another blood test in a week (that will be 3 weeks from the initial test) and we're all hoping that the levels were aberrations. If they're not, what would you suggest we do next, x-rays? Ultrasounds? With both the calcium and liver enzyme elevated, can it be assumed that the liver would be the most likely place to start or could other conditions conceivably cause this---hyperthyroid, parathyroid abnormalities? Am I just being paranoid or would a liver biopsy be a consideration at this stage? Katie shows absolutely no symptoms of anything--but I know many animals don't in the initial stages of a disease like lymphoma.
When we lost our Winchester to lymphoma, it broke our hearts--especially since his doctors thought his early diagnosis and relative good health gave him a better-than-average chance of beating the disease. Katie has youth on her side and if we can give her a shot at a longer life, we'll do anything we can.
We'd really appreciate your insights and advice. Thank you! Pat
There are two problems in the lab work reported in your note. The first is a mild hypercalcemia and the second is the elevation in the ALT value. It is probably best to look at these as separate problems, at least at first. Rechecking the blood work is a good first step, because calcium levels are probably the least reliable of the blood chemistry tests, at least from our lab. It isn't unusual at all for us to find a high calcium level that is never repeated on subsequent testing. It is best, when possible, to test for ionized calcium levels when hypercalcemia is present, because this is the active form of calcium in the body and it helps to know if it is being regulated properly even though total calcium is high.
Hypercalcemia in cats does not have quite as strong a link to cancer as it does in dogs. There are several causes of hypercalcemia in cats, including metastatic cancer, kidney failure, idiopathic hypercalcemia and primary hyperparathyroidism. Except for hyperparathyroidism, these conditions are fairly close to equal causes of hypercalcemia in cats, with cancer and kidney failure having a slight edge over the idiopathic hypercalcemia, which is closely tied to the presence of calcium oxalate bladder stones in cats.
Idiopathic hypercalcemia is called that because no one knows for sure why it is occurring. It seems more common now than in the past and there is evidence, based on the University of Minnesota's long term collection of uroliths (stones in the urinary system) that it really is an increasing problem, rather than just increasing recognition of an old problem. The best screening test for this problem is probably X-rays of the urinary tract to look for the presence of bladder stones or stones elsewhere in the urinary system. This problem may be related to the use of acidifying diets (used to try to avoid feline lower urinary tract disorder, a different urinary tract disorder). If a urolith is identified, then treatment can be aimed towards controlling that problem.
Kidney failure in cats is another common cause of high blood calcium levels. Usually, the lab work would have clear signs of kidney failure, such as increases in the blood urea nitrogen (BUN) and creatinine levels. Since that doesn't seem like the case, this is less likely to be the problem.
Hyperparathyroidism is not especially common in cats, but it was the cause of hypercalcemia in about 6% of the cats in a study of the causes of hypercalcemia in 71 cats by Savary et. al (2000) from NC State. Testing for parathyroid hormone levels can help to rule out this problem. Normal or elevated parathyroid hormone levels in the face of elevated calcium levels, especially elevated ionized calcium levels, would be a strong indication that this was the problem. Low serum phosphorous levels are also expected with primary hyperparathyroidism, although they also occur when malignant cancers are the cause of the high calcium levels.
The two cancers most commonly associated with high calcium levels in cats are lymphoma and squamous cell carcinoma. It is worthwhile to search for these cancers if the calcium levels remain high and there is no evidence to support the previously mentioned differential diagnoses. A good physical exam is probably the best way to identify squamous cell carcinoma, although it may require anesthesia to look in some places this cancer frequents, such as the back of the mouth and the nasal passages. Ultrasound examination of the intestinal tract, spleen and liver might indicate the presence of lymphoma and is probably the best screening test. Rechecking for feline leukemia virus infection would be a good idea if this tumor remains a suspect, as well. It seems a little strange that there are no clinical signs that might be linked to lymphoma, though. Many cats have persistent vomiting or diarrhea with intestinal forms of lymphoma, weight loss or signs of other problems with other forms. If signs of gastrointestinal disease do occur it may be helpful to have an endoscopic examination of the digestive tract and to obtain biopsy samples in this manner. Lymphoma is sometimes confused with other problems using this approach, due to the superficial nature of the biopsy samples that can be obtained, but it is still a reasonable test procedure.
The elevation in the alanine transferase (ALT) occurs when there is damage to liver cells. This can happen for a number of reasons. Medication reactions, toxins, cancer and hepatic lipidosis are probably among the most common causes in cats but there are also lots of times when the ALT rises for no apparent reason and then is normal on testing after a week to a month or so. In the absence of any recognizable disease it is probably best to do exactly what your vet advised, recheck the levels after a reasonable interval and then decide what to do if the ALT remains elevated. If the cat is not eating well, waiting is not as advisable. In this case, an effort should be made to rule out hepatic lipidosis as quickly as possible and to provide adequate energy to prevent its occurrence as a secondary problem as time goes on.
If the ALT does stay elevated, this would be another reason to consider ultrasound examination, since it is non-invasive and may be useful in determining what is going on. We tend to do a fine needle aspirate of the liver to check for hepatic lipidosis, since it can often be recognized by this test, which is pretty safe for the patient. Then we might do bile acid response testing or we might elect to refer for other testing, such as ultrasound exam and ultrasound guided biopsy, as long as blood clotting it normal. Some pets have persistently elevated ALT values with no evidence of liver disease by symptoms, physical exam, X-rays or ultrasound exam and no decrease in liver function on bile acid response testing. It is reasonable in these pets to monitor ALT (and a serum chemistry panel) on some reasonable schedule, like every 3 to 6 months, just to be sure that a disease process doesn't become evident over time.
The presence of both hypercalcemia and increase ALT does make the suspicion of cancer stronger, since it could cause both problems. It wouldn't surprise me too much if the lab work is normal the next time, though. It is a little strange to have aberrations in more than one value in a lab sample but it happens often enough that the conservative approach of rechecking the values in a patient who seems to feel good makes a lot of sense. It also seems possible that the hypercalcemia could be the idiopathic syndrome seen in cats and the ALT rise due to a decrease in appetite leading to hepatic lipidosis or of some other complication associated with that condition.
I hope that this helps some with your thought process in working through the possibilities, if the lab values for these two conditions continue to remain high.
Mike Richards, DVM
Blood acidosis and TCO2 critical levels
Question: Hi Dr. Mike,
Just want to tell you how much I have appreciated your web site. It is a great asset to the internet.
I have a 13 year old neutered male kitty named Velcro. He is a very sweet boy, and has had a rough year and a half, all of which I will write out in an email in the near future for your opinion. However, the immediate problem is that he recently (two days ago) had a blood test done which showed a TCO2 (bicarbonate) level of 9 (13-25 normal) and an anion gap of 33 (13-27 normal). He has been on 10 mg/prednisone a day for several months for a not totally confirmed benign brain tumor (no MRI--based on symptoms and other extensive tests--I'd already spent $2700 on him, and just couldn't afford the MRI). I had tried to reduce it gradually to 5 mg/day, but he appeared to have a small seizure.
Anyway, he has had sporadic diarrhea for the past month, which I attempted to treat progressively with Kaopectate, Imodium AD, and Flagyl, along with some anti-allergy type canned food from the vet (duck and venison). His diarrhea only got worse, turning to total liquid. So the vet prescribed Eukanuba low residue food, and I am gradually taking him down to 7.5 mg prednisone/day.
My question are these: The vet thinks the acidosis may be caused by the diarrhea, and I agree. She also thinks the prednisone may be causing the diarrhea, which is why we're reducing it (and may again try going down to 5 mg/day). Is it possible that the prednisone alone could cause acidosis? Also, how low can TCO2 go before it becomes life threatening? I feel that I may have to decide if he is going to pass from brain swelling or acidosis.
Thank you for your help. I will post his full history in a hopefully somewhat succinct fashion in the next few days.
Gayle and sweet Velcro
A total CO2 level less than 12 mEq/L is considered to be dangerous, so 9 is definitely in the range in which acidosis is likely to be a major problem, if it is not an artifactual value.
The lists of medications that are likely to cause decreased TC02 that I have seen do not include prednisone. The medications that seem most likely to cause problems with this are ammonium chloride and tetracycline. If there is a delay in measuring the TC02 in a sample, it may falsely decrease the TC02 of the sample. I can't be certain that prednisone couldn't cause acidosis but it must not be a common cause unless I just missed something.
The two causes of low TCO2 that are clinically important are metabolic acidosis and respiratory alkalosis. The most common causes of respiratory alkalosis sufficient to cause a low TC02 are lung diseases (pneumonia for instance) or pleural effusions. The patient is usually in obvious respiratory distress when the disease is sufficient to cause a significant drop in TCO2, though. Metabolic acidosis is caused by ketoacidosis from diabetes, urinary blockages, kidney failure, anti-freeze poisoning, aspirin toxicity and dehydration (usually has to be severe). If dehydration was caused by diarrhea the TCO2 could drop. I am not sure whether diarrhea alone would cause a significant acidosis in a patient compensating for the fluid loss since vomiting usually causes rises in the TCO2 and I haven't seen much written about what diarrhea does.
A small increase in the anion gap in cats is often due to a decrease in potassium, if it wasn't compensated for in the formula used. This can occur from diarrhea or be an early sign of kidney insufficiency. Decreases in other cations, such as calcium and magnesium can do this, as well. On the flip side, increased "normal" anions like lactate, ketoacids, albumin and phosphate; or really bad stuff like ethylene glycol (anti-freeze), methanol and salicylates in the serum can lead to increases in the anion gap.
The reason for these changes is that the anion gap is a formula that only includes the major players in the positive and negative ionic mixture. Several formulas have been used to calculate the anion gap -- the two I am familiar with are (Sodium + Potassium) - (Chloride + Bicarbonate) OR Sodium - (Chloride + Bicarbonate). There are other cations and anions in the serum but these exist in small quantities (even potassium is small enough to leave out of the one formula). The anion gap increases when another anion type chemical is present in large enough quantities to screw up the formula or when the cations are low enough to impact on the formula.
Since you have probably been measuring electrolytes as part of lab panels, it seems unlikely that diabetes or severe kidney failure would be present and unnoticed, taking away the most likely suspects in an elderly cat and I suspect that you would have seen clinical signs of severe respiratory disease. So I guess I'd have to go with you and your vet on the diarrhea as a probable cause. We do sometimes see patients who have pretty severe diarrhea from prednisone use. For reasons I can't explain it sometimes helps to use a different form of corticosteroid, like dexamethasone or methylprednisolone. When we absolutely have to use a corticosteroid and diarrhea is present it seems to help sometimes to give a little plain yogurt daily or to use a probiotic preparation and sometimes we try concurrent antibiotic use with some success.
I hope that you are seeing improvement. Cats and most other species have tremendous ability to compensate for acid-base imbalances if they just live through the crises. Hopefully Velcro is doing better.
Mike Richards, DVM 2/13/2001
Hemolytic anemia or immune mediated thrombocytopenia (ITP)
Question: Dear Dr. Mike,
We are new subscribers from the UK to your service and we have an urgent request for your help and advice.
Our female cat, Billie, is 9 years old and diagnosed as having Haemolytic Anaemia 6 weeks ago. At that time, our local vet prescribed the following:- 1 x Cyclophoshamide every 2 weeks 1 x 5mg Prednisolone twice a day 1 x 50mg Cimetidine twice a day plus a course of Danazol for 2 weeks.
Billie's condition improved significantly and her red blood cell count was up to 35. 2 weeks ago, her red cell count fell to 31 and on Thursday, this week, fell further to 20. Our vet advised us that there was nothing further that could be done but, after much argument, eventually contacted another Veterinary Hospital in Cambridge (England) to get further advice.
Yesterday (Friday 15th), we were given instructions for the following increased medication:- 3 x 5mg Prednisolone twice a day 2 x 20mg Ronaxan twice a day (although no parasites had been apparent in blood tests) 1 x 50mg Cimetidine twice a day 1/4 tablet Suralfate (Antepsin) 3 times per day
I requested that Billie be given Danazol or some similar inhibitor but the vet refused, saying that the drug will cause liver failure and they were unwilling to prescribe Danazol again.
Please would you advise me whether you feel that Billie has been prescribed the correct medication and whether Danazol would be severely detrimental. Blood tests have been done every week for 6 weeks but the vet is unable to find the reason behind Billie's condition.
Five months ago, she received Radio-Iodination treatment for Hyperthyroidism. Is it possible that this could be a cause and is it possible that she has parasites in her blood but that these are being missed, or not traced, in her blood tests?
Today, Billie is very lethargic - the new increased drug schedule having started yesterday.
Any information or advice you can give will be very much appreciated as our vet seems to be unfamiliar with this awful disease.
With many thanks, Michelle
Hemolytic anemia in cats can be caused by blood parasites and it can be hard to find Hemobartonella, the blood parasite seen most commonly in cats, even when there is a high degree of suspicion for it. In the U.S., I think the most commonly recommended antibiotic for hemobartonellosis would be doxycycline. I am not sure what Ronaxan is, but if you can supply a generic name I might be able to give you more information on it. I think it is reasonable to treat for the suspicion that hemobartonellosis is present and that is probably what your vets are doing.
There are a lot of reports of Danazol (Rx) causing liver problems in cats. I would be very reluctant to use it, even though your cat didn't have problems with the first round of treatment.
Prednisone dosage may need to be as high as 8mg/kg to successfully treat immune mediated thrombocytopenia or immune mediated hemolytic anemia in cats, so even though the dosage of pred recommended is high, it probably isn't beyond the maximum recommendations at this point. The use of protective agents for the GI tract is common when administering dosages of prednisone in this range, which is probably the reason for the cimetidine and sucralfate. In cats it is usually recommended to push the corticosteroid dosage rather than switch to other immunosuppressive agents until it seems certain corticosteroids won't help, since other immunosuppressive agents tend to be more toxic in cats than in dogs.
The reason I mentioned immune mediated thrombocytopenia (ITP) is that your original vet's treatment plan seemed geared towards that problem, so I am a little concerned that it may be the problem rather than hemolytic anemia. If this is the case, a common cause of platelet deficiency in cats is bone marrow suppression from feline leukemia virus (usually) or feline immunodeficiency virus (less likely).
I have not heard of a correlation between radioactive iodine therapy for hyperthyroidism and either ITP or IMHA in cats. I can't say that it couldn't have contributed to this problem but it would be unusual, I think.
I hope that the new medication recommendations are helping or will help soon. If you have further questions or need clarification of anything in this note, please feel free to write again.
Mike Richards, DVM 4/18/2000
Anemic and vomiting blood
Q: Our kitty Misha came with our house purchase. We believe he is about 8 years old and he weighs 14 lbs. For the 4 years we have had him, he has been an indoor cat. He is our only cat and since last August, has received 3 treatemtns of Advantage so he doesn't have a problem with fleas. Last week he vomited an hour after his morning meal and the vomit was full of blood, at least a half cup or so. My regular vet referred me to another vet who had an endoscopy machine. The vet looked in his stomach for possible ulceers but didn't find any ulcerations. Given the amount of blood he vomited, he performed exploratory surgery and checked for any blockage in his intestines. He didn't find anything other than a small mass in the secum which when dissolved in water was just grit and blood. The medications given were barium, reglan and carafate. Two days before he was scheduled to have his stitches removed, I came home Wednesday evening to find him weak with his pupils dilated. He had been perfectly active, eating well, etc. up to that night. I rushed him to the vet and when they tested his blood, they found him anemic. The vet guessed the blood was probalby leaving through his stools. He was given blood transfusions on Wednesday night and kept for observation. The chest x-ray is clear, there is no blood in his stool, there is no fluid around his belly area to account for internal bleeding. He was given blood transfusions on Wednesday night and although his count went up, it went down again. The results for feline leukemia are negative. He is now on an IV, prednizone, tagamet, barium and carafate. My regular vet thinks it sounds like an auto-immune disease of sorts. Most of what I have read indicates these diseases show up with time, not suddenly in less than 8 hours. Given that this is a pampered, strictly indoor cat, I cannot imagine how he could have been contaminated by another cat. He has not had any weight loss. What information is known about allergic reacitons to medications that could cause this anemia? One of our friend's mother had something like this due to a stroke medication, Teclid, which caused her to have transfusions for over a month. The Teclid took a long time to leave her system. What are the possibilites that our cat could have an allergy to one of the medicatons he got after the exploratory surgery? Needless to say, like many pet owners feel, he is our baby. Any comments? G.
A: I would be most concerned about a bleeding disorder such as exposure to rat or mouse containing an anti-coagulant in this situation. If this hasn't been ruled out, it would be worth asking your vet about. Liver disease can lead to problems with blood clotting. There are some platelet disorders that affect cats, too. In dogs, heartworm disease can lead to coagulation disorders but I do not know if this is seen in cats with heartworms and that seems unlikely in your cat's case, anyway.
None of the medications you listed are associated with bleeding disorders that I know of but that is a good thought -- all things like this have to be considered.
Auto-immune disease is certainly possible, too. I think your vets probably considered the above possibilities but it doesn't hurt to ask.
I wish I could help more. This is definitely a situation in which you need "hands on" help. Mike Richards, DVM
Cat Blood Types
Cats have A, B and AB (rare) blood types. Most cats in the United States have type A blood - something like 99% of domestic shorthair cats have Type A blood. This ratio varies from country to country. Other cat breeds have a much higher incidence of Type B blood. As the popularity of purebred cats increases it is likely that the ratio of cats with Type B blood will also increase.
There is no "universal donor" blood type in cats - a very small amount of the wrong blood type can kill a cat if is is sensitized to the blood. This can be an issue in some cat breeds. In particular, British Shorthair, Cornish Rex and Devon Rex cats, where the percentage of Type B cats is much higher, perhaps as high as 50%. Other breeds with significant percentages of Type B blood include the Abyssinian, Himalayan, Japanese Bobtail, Persian, Somali and Sphinx breeds. (preceding information from Urs Giger, University of Pennsylvania, Kirk's XI).
If a Type B queen (mother cat) gives birth to Type A kittens, severe reactions can occur in the kittens. Type B cats have strong antibodies against Type A blood. These antibodies are passed in the milk, which is very bad for any kittens that are Type A. Since A is the dominant blood type, this means that most of the kittens born will be Type A when a Type A father breeds with a Type B mother. Neonatal isoerythrolysis-- destruction of the kitten's red blood cells by the antibodies in the mother's milk -- is very likely to occur. In breeds in which significant percentages of Type B blood occur, it is wise to know in advance what the blood types of prospective parents are. Your vet can arrange to have blood types tested. Mike Richards, DVM
Type B Blood
Q: I breed Maine Coons and have just found out one of my kittens in a litter has type Bblood. This kitten has been sold as a breeder. Please advise how this happened as I have been unaware of this in my cats in the past. I am not learned on this subject and how would I produce a type B kitten.? Is it possible please to E-mail me also as I will probably never find the answer on this site. Thanks so much. K.
A: Cats with type B blood seem to be more common in purebred lines than in the general population. Cats can be type A, type B, type AB and very rarely type AE. Type A is dominant to AB which is dominant to type B. In order to get a type B cat when no one else is type B it is highly likely that you have bred two type AB cats (or else you have a type B cat you don't know about).
The people planning to breed this kitten in the future will need to be careful with their breedings. Cats with type B blood form anti-bodies against both A and AB blood types. Kittens born to these cats who are type A or AB absorb antibodies against their own blood from the mother when they nurse for the first time. This causes problems in the kittens ranging from sudden death to severe illness to less severe problems like loss of the tips of tails. Mike Richards, DVM
Last edited 01/30/05
Michael Richards, D.V.M. co-owns a small animal general veterinary practice in rural tidewater Virginia. Dr. Richards graduated from Iowa State University's College of Veterinary Medicine in 1979, and has been in private practice ever since. Dr. Richards has been the director of the PetCare Forum...