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Polycythemia In Dogs

DOXIELOVER5
March 21st, 2008, 11:12 PM
Hi to all. First time here.
We have a 9 yr old Dachshund named Friday.:dog: He and 4 other Doxies run our home.
Friday has had some shortness of breath for the last 6 weeks. After blood work and many other tests our vet determikned he has Polycythemia Vera.
Looking for others that have had dogs with this condition.
What has been cause, treatment and prognosis. Trying to get as much info as possible on this. Worried sick.
Any advise, info. ect. would be appreciated.
Thanks, and Happy Easter to all that celebrate this day.
God Bless.
Sharon


"Dachshunds leave footprints of love on your heart"

Chibi
March 21st, 2008, 11:17 PM
I've never dealt with this problem, but I have a little dachshund of my own, and just wanted to wish you luck.

DOXIELOVER5
March 21st, 2008, 11:22 PM
Thanks for the good wishes. Hope we will get some answers. I worry about my furkids.

Sharon






"Dachshunds leave footprints of love on your heart"

rainbow
March 22nd, 2008, 01:00 AM
I am sorry to hear about Friday. :grouphug: I have no experience with Dachshunds but SnowDancer (a member here) does have lots. I'm sure she will log on with her advice soon. :goodvibes:

SnowDancer
March 22nd, 2008, 12:17 PM
Hi DoxieLover, I am so sorry to learn of your pup's diagnosis. I wish I could offer some advice, but I think this is about the only health problem my guys didn't go through - we are serious experts in neck/back disease. Are you being referred to a specialist? Does your vet have experience with this condition? My vets had a lot of Dachshund experience - and a heck of a lot more after dealing with my guys and the referrals to neuros etc. We also had 4 Dachshunds at one time - with the first and the last - the 2 who suffered the worst case back problems and surgeries - being serious, but benevolent Alphas who ruled the roost. Please let us know how your pup is doing. Have you tried posting on a Dachshund specific board? Sometimes you can get some good ideas there, even if you just lurk. I do that on an American Eskimo board just to see what is happening with the breed.

SnowDancer
March 22nd, 2008, 12:53 PM
I just googled you pup's diagnosis to confirm that it was what I was thinking. While I was careful to add the word "Canine" I still did find many references to the human form of the disease. I would definitely be very worried, but your post didn't indicate the level of the disease or your vet's prognosis. Is Friday's condition treatable and if so what would be the toll on Friday's everyday life and expected lifespan? Without knowing this, it would be hard for people to really give you the benefit of their experience. I really hope it is a mild form and is treatable.

Dr Lee
March 22nd, 2008, 02:08 PM
Sorry to hear about what is going on. I don't know if this is what you are looking for but here is medical lecture from a conference for veterinarians regarding polycythemia vera. I realize this is written in 'Greek' but I figured more info is better than less. Also please remember that this info is given to help you to understand. If you veterinarian has not run every test here or done it exactly like this - please remember that the diagnosis, management and treatment is NEVER EXACT to a conference lecture. Each case is individual and needs to be specifically taylored.

Hope it helps.:pawprint:

ACVIM 2003
Urs Giger, DACVIM, DECVIM
Philadelphia, PA

INTRODUCTION AND DEFINITIONS

Although strictly speaking polycythemia implies a rise of all blood cell counts above normal, the occurrence of leukocytosis and thrombocytosis along with erythrocytosis is exceptionally rare in animals. Hence, polycythemia would be more appropriately called erythrocytosis and clinically refers to an increase to an above normal red blood cell count, hematocrit (PCV), and hemoglobin (Hb) concentration. Polycythemic animals will not show clinical signs until the PCV reaches >60% with some of the highest PCVs exceeding 85%. Because of an underappreciation of the normal upper limit of the PCV in cats (45%) versus dogs (55%), polycythemia is generally underdiagnosed in cats. Based upon blood volume and red cell mass, polycythemia can be divided into relative and absolute polycythemias, which represent completely different conditions, both requiring immediate but opposing therapeutic interventions.

Relative polycythemia is characterized by an elevated PCV in the presence of a normal (or even decreased) total red blood cell mass. This is usually due to a decrease in plasma volume associated with severe dehydration or increased serum total proteins, as in such conditions as profound vomiting and diarrhea, or severe burns. The hematocrit is generally only mildly increased, therefore relative polycythemia is rarely associated with signs of hyperviscosity, and the clinical features of the underlying disorder prevail. Because of the obvious signs of dehydration, relative polycythemia is easily recognized and simply corrected with aggressive fluid therapy.

Absolute or true polycythemia is characterized by an expanded red blood cell mass. Splenic contraction is an unlikely cause in dogs and cats, as it only marginally increases the PCV. The blood volume and red cell mass could be determined by labeling red cells radioactively or with biotin. This is, however, rarely if ever needed in clinical practice, as dehydration can be readily excluded as cause of relative polycythemia. More difficult is the differentiation of absolute polycythemia into primary or secondary polycythemia, which depends on whether the condition is erythropoietin independent or dependent.

Some clinicians readily equate absolute erythrocytosis with polycythemia vera (P. vera) without considering other differential diagnoses. Recent studies and clinical experience, however, suggest that P. vera may occur rarely compared to other forms of polycythemia. New insight into the causes of primary and secondary polycythemias has been gained in human medicine, which will be presented along with the limited experience in small animal medicine. However, if the underlying condition cannot be corrected, lowering the PCV into a safe range in patients with absolute polycythemia may be successfully accomplished with repeated phlebotomy and, if needed, chemotherapy.

PRIMARY POLYCYTHEMIA

Primary polycythemia appears erythropoietin independent and has often been considered synonymous with P. vera in small animals, although additional forms of primary polycythemia need to be considered. In fact, based upon recent studies of serum erythropoietin in animals with a presumptive diagnosis of primary polycythemia, as well as cases with an early presentation in life that continues over a chronic course of many years, point strongly to the existence of other forms of primary polycythemia in dogs and cats. In some human patients and in isolated families, mutations have been identified in the erythropoietin receptor that causes an erythropoietin hypersensitivity resulting in primary polycythemia. Furthermore, mutation in the erythropoietin gene may impact its efficacy inducing erythropoiesis, which would lead to the appearance of a polycythemia that is erythropoietin independent. More research is needed in small animals to determine, if such processes are occurring in these polycythemic patients who do not clearly have P. vera.

Polycythemia vera is a myeloproliferative clonal disease that arises from a multipotent hematopoietic progenitor cell in the bone marrow. A single transformed stem cell gains a selective growth advantage and becomes the predominant source of marrow precursors, and the clonality of the bone marrow cells of human patients with P. vera has been documented. P. vera, therefore, results in the accumulation of morphologically normal red blood cells, and less commonly white cells and platelets, and their progenitor cells in the absence of a definable stimulus. Granulocyte and platelet counts in the blood would be expected to be increased, but are usually normal. The bone marrow aspirate is consistent with erythroid hyperplasia, but is not diagnostic for a myeloproliferative disease in humans. There are no cytologically characteristic features of the bone marrow cells in P. vera as hematopoietic cells appear to fully mature. Classically, human patients have serum erythropoietin levels in the low to normal range and erythroid progenitor cells that proliferate and mature independent of erythropoietin, but these culture assays are not robust and readily available.

In humans, there is some evidence for both gain and loss of suppressor genes in P. vera, but the precise mechanisms that affect the progenitors' behavior remains to be elucidated. The erythropoietin receptor expression and ligand binding were not different in erythroid cell lines from P. vera patients compared to normal cells. Recently, overexpression of PRV-1 mRNA, a novel hematopoietic cell surface receptor, has been found in granulocytes of all human patients with P. vera, but not other forms of polycythemia. However, the amount of PRV-1 protein expressed on the cell surface is not significantly different between patients and controls. Thus, further studies are needed to confirm the relationship and diagnostic value in human and veterinary medicine. Finally, over time there appears to be a risk for the development of myeloid metaplasia and transformation into leukemia in humans with P. vera.

Hence, the diagnosis of P. vera is still based on the exclusion of other causes of erythrocytosis and criteria set forth by the Polycythemia Vera Study Group. It requires the documentation of an increased red cell mass with a normal arterial oxygen saturation and either splenomegaly or two of the following abnormalities: leukocytosis, thrombocytosis, increased leukocyte alkaline phosphatase activity and high serum cobalamin concentrations. The clonality culture assay and high PRV-1 mRNA in granulocytes have yet to be included as criteria.

SECONDARY POLYCYTHEMIA

Secondary polycythemia refers to a group of diseases triggered by an exaggerated erythropoietin dependent stimulation of red cell production. This may be considered an appropriate response in which the erythron is responding normally to generalized tissue hypoxia or inappropriate in which the erythropoiesis is being stimulated by an aberrant production of erythropoietin or due to local renal hypoxia.

Appropriate PCV rises are seen in high altitudes and with cardiopulmonary disease such as congenital heart defects with right to left shunts (ventricular septal defects, reversed PDA, Tetralogy of Fallot) and rarely chronic obstructive pulmonary diseases. Cats with cardiac shunting usually die before they can develop signs of polycythemia. Furthermore, an appropriate secondary polycythemia has been documented in several breeds of dogs and domestic shorthair cats with hereditary methemoglobin reductase deficiency, which results in the erythrocytes' inability to carry oxygen. Abnormal hemoglobins that are unable to properly transport (M-hemoglobin) and release (low 2,3-diphosphoglyceride concentrations or high affinity hemoglobins) oxygen may also need to be considered, but have not yet been documented in companion animals.

Inappropriate absolute polycythemia includes renal diseases, as well as tumors producing erythropoietin, and is typically associated with high serum erythropoietin levels. Various renal tumors, including nephroblastomas and carcinomas, may result in renal hypoxia and thereby cause elevations in serum erythropoietin and, consequently, inappropriate secondary polycythemia; whereas erythropoietin-producing tumors in other tissues have rarely been documented. Recently increased amounts of erythropoietin mRNA and protein have been found in tissue of a cecal leiomyosarcoma from a polycythemic dog, thereby providing definitive proof of ectopic erythropoietin production. In humans, cutaneous and uterine leiomyomas have been shown to produce erythropoietin. As fetal erythropoietin is produced in the liver, hepatic tumors including carcinomas and hepatoblastomas can rarely be producing excessive amounts of erythropoietin and be associated with polycythemia. Inappropriate secondary polycythemia of renal origin may also be rarely caused by amyloidosis, polycystic kidney disease, glomeronephritis, and renal fibrosarcoma and lymphoma. In most cases increased serum erythropoietin concentrations were documented or an association was established based upon the resolution of the polycythemia following the resection of the mass in animals and humans.

CLINICAL SIGNS

The clinical signs of relative polycythemia are easily recognized and will not be further discussed here. Clinical signs of absolute polycythemia are characterized by manifestations of the underlying disease process and are associated with hyperviscosity and the expanded blood volume. They include hyperemic or cyanotic mucous membranes (due to cardiopulmonary disorders and methemoglobinemia), hemorrhage (epistaxis and hyphema) and neurologic disturbances such as lethargy and seizures. Neurologic signs are the most common presenting complaints, but with the advent of more frequent health screens including complete blood cell counts, the erythrocytosis may be discovered earlier as an incidental finding. Cyanosis or renal size abnormalities may suggest a particular organ failure as well as mechanism, and define the type of the polycythemia. However, secondary cardiac and renal changes due to erythrocytosis may also be observed and confound the interpretation.

In humans P. vera usually has an insidious onset. People with P. vera are often in their sixties, although it may occur earlier. Some patients are diagnosed simply because of abnormal cell counts on routine screening, albeit some may not be recognized until a catastrophic event occurs due to the hyperviscosity. Typical signs in humans include headache and other neurologic disturbances, hypervolemia, pruritus, splenomegaly, thrombosis, and gastrointestinal bleeding. Splenomegaly has been seen in humans and animals assumed to have P. vera and rarely with other polycythemias. Neither the degree of thrombocytosis nor presence of platelet dysfunction has been correlated with the risk of thrombosis in humans. The thrombotic tendency is not well documented in small animals but may be evident at the site of venipuncture for phlebotomy. Furthermore, it is difficult to know what the natural course of the disease is without the various therapeutic interventions that undoubtedly influence it. Some dogs and cats presumed to have P. vera live for more than a decade, and rarely the polycythemia regresses spontaneously.

Diagnostic Tests

As relative polycythemias are readily recognized, confirmation of a normal blood volume may not be required in clinical practice. In fact, patients with absolute polycythemia often have an expanded blood volume. Diagnostic tests for absolute polycythemia include a complete blood cell count, absolute reticulocyte count, chemistry screen, urine analysis, blood gases and pulse oxymetry, chest and abdominal radiographs, cardiac examination and an ultrasound to evaluate the kidneys and liver. Serum erythropoietin values, determined by a species-validated assay, may be elevated in cases of secondary polycythemia, but a normal to low erythropoietin level does not rule out secondary polycythemia. An increased absolute reticulocyte count in light of a polycythemia supports the exaggerated hematopoietic response and documents the presence of an absolute polycythemia. However, a bone marrow aspirate for cytologic examination adds no new information, since it fails to differentiate between primary and secondary polycythemias: the myeloproliferative disease resulting in P. vera has no characteristic cytologic or pathologic features of malignancy. Bone marrow cultures in the presence and absence of erythropoietin to document erythropoietin dependency require special expertise and are only available in a few laboratories. The documentation of high serum cobalamin levels and overexpressed PRV-1 mRNA as well as increased alkaline phosphatase concentrations in granulocytes has not been systematically assessed in the diagnosis of animals with polycythemia. Special erythrocyte studies (electrophoresis, diphosphoglyceride, methemoglobin) may be useful in certain cases, but are not readily available. The author's laboratory has established collaborations to pursue some of these studies.

Treatment

The treatment of relative and absolute polycythemia is clearly different. In emergency situations, patients with relative polycythemia will respond to fluid therapy, whereas patients with absolute polycythemia may need to be treated by phlebotomy. If possible, renal and other tumors/masses should be removed or treated and cardiopulmonary distress should be corrected. Animals with methemoglobin reductase deficiency may not need to be treated except during severe stress situations with new methylene blue (1mg/kg IV once). In severely polycythemic patients repeated phlebotomies at no more 20 ml/kg per session with or without simultaneous fluid replacement is the initial approach to lower the PCV to <60%. Phlebotomies can be repeated on a daily basis until the target PCV has been reached. In animals with absolute polycythemia, fluid administration beyond replacement may be associated with cardiopulmonary failure as these animals are completely volume expanded. In cases that require multiple phlebotomies in a short period, replacement of coagulation factors and albumin with plasma may need to be considered. The target hematocrit is higher in dogs than in cats, as well as in cases with cardiopulmonary disease, but generally is greater than 50%.

Longterm control of absolute polycythemia may be achieved by periodic phlebotomies, radioactive phosphorus, and/or chemotherapy. In humans with P. vera, no treatment has offered better survival than repeated phlebotomies. Chemotherapy with hydroxyurea at 10-25 mg/kg twice daily to once every other day is commonly used. Alternative chemotherapeutic agents are chlorambucil, busalfan, and pipobroman, but like hydroxyurea, all have the potential to induce secondary tumors including leukemia. Animals treated with chemotherapy need to be monitored, not only by PCV measurements as for phlebotomized patients, but also by complete blood cell counts to identify drug induced cytopenias. Hydroxurea has also caused nail sloughing. Interferon alpha is another approach to control the red cell production in humans with P. vera. Furthermore, antithrombotic doses of aspirin (1 mg/kg per day) may be considered, but there is no proof that it reduces the risk of thrombosis, and higher doses may lead to increased bleeding tendencies. Polycythemic animals may remain asymptomatic for weeks to years and, in some cases, can be successfully managed for years. Longterm follow up has not been reported in animals, although the author has observed persistent polycythemia for more than a decade in certain animals.

DOXIELOVER5
March 22nd, 2008, 02:32 PM
Thanx you Dr. Lee for the info on Polycythemia Vera. Gave me a real understanding to the situation. I'm a retired R.N. so most of it I understood.
Friday will be going in again next week to discuss treatments. I know most of them have a high risk, which causes me much distress.
Someone had suggested aspirin therapy. Any thoughts????
R.B.C. was high, Plat. normal, wbc low, BUN & creat. normal.

Thanx again for all the info. Stay in touch

Sharon



"Dachshunds leave footprints of love on your heart"

Dr Lee
March 22nd, 2008, 02:52 PM
Please ask your vet on the aspirin before giving it.

There is a lot of controversy regarding aspirin and I am personally not a fan of aspirin. There are a many new medications that can do the same job now. Some are also human only labeled. Aspirin is not Cox-1 sparing and dogs are much more sensitive to it. The reduction in kidney/renal blood flow is more pronounced with dogs versus people. Stomach erosion and ulceration is also more pronounced.

On the other hand, I have several patients on aspirin. So sometimes it can be very useful. I do recommend pepcid (famotidine) to be given concurrently to protect the stomach and omega 3 fatty acids to help protect the renal function. I am a big promoter of omega 3 fatty acids for everyone!

Good luck!:pawprint:

DOXIELOVER5
March 22nd, 2008, 05:36 PM
I agree with what you said about aspirin.
I have all 5 of my Dachshunds on Omega 3 suppliments each day. I also take it every day due to the strict eating program I have put myself on, starting April of last year I have lost 163 lbs. as of today. Have another 20 lbs to go. I am very fussy about the pups nutrition, as my own.
Thanx again for getting back to me so fast on this.
I do Dachshund rescue and had did Sea Lion Rescue work also.
Friday was my first rescue Doxie and he remained in a forever home with us.
Kind of like my first child. He has a special spot here.
Hate to see him so short of breath and kind of slowing down. Breaking my heart...
Thanks again for the help. This is an awesome site. Everyone is wonderful.:thumbs up

Sharon


"Dachshunds leave footprints of love on your heart"

DOXIELOVER5
March 23rd, 2008, 08:00 AM
Good Morning Dr. Lee.

It's early, can't sleep. Happy Easter.

Friday sleeps with me so I find myself listening to his S.O.B.
SOB started about 6-8 weeks ago. Friday has always been in good health, a little overweight, but no other problems.

His vet has treated him with Lasix, Steroids, Antibiotics. Thought it was COPD at first. Xrays on chest looked ok. Heart, kidney, spleen & ab all looked good. Tests also showed blood in urine, none in stool. No worms in blood or stool. Membranes are pink.

We live in a rural area in Medford Oregon. We moved here from So. Calif 7 years ago after my husband retired.
Our vets are wonderful but are puzzled on this as they have had very little experience with this condition.
They do not even have the right cath. to do the phlebotomy procedure.

Could I beg your opinion as to what would be the best and safest procedure for Friday. Chemo drugs vs. phlebotomy? Or any other method.

What will be the risks to Friday on any treatments?

We are open to trying ANYTHING. I just can't lose my dog at this time, yet I do not want him to suffer. I'm very concerened as to what he is feeling right now.

I lost my 2 old cats last year and 2 other Doxies over the last 6 yrs. We have picked the time for the trip to The Rainbow Bridge when they have become to ill to have a quality of life. They have all died in our arms with all our family with them. They have all been creamated and remain with us.

My husband George is dying. He is in renal failure and has lost his leg among other health problems. He is also losing his will to go on. If Friday goes, that will be too much for my husband to take in his fragile health & mental state..

We love this dog soooo much. He and our 4 other rescue Doxies are all whole life. He is our #1 boy. (We just don't tell the other ones!!) We also run a food bank for the poor, to give back to God for all he does for us.

Since vet care is good but limited here, we would be willing to go anywhere for treatment. We are both on Social Security, but will find a way.

Just want to tell you how much your advice has meant to us. You have given us more info, than we have received in weeks.

I just hate to keep picking your brains, but your the only person that I have spoke with that has the knowledge and compassion and genuine concern to offer the advise that you have given me. I'am so grateful.

Please Email me when it's good for you. I hope you and your family have a wonderful Easter. (Please accept my apology if you do not celebrate Easter, I do not want to offend anyone.)

You can also reach me at webedoxies@charter.net

This is a wonderful forum, so many nice people on this site.

Thank you again Dr. Lee for your help. Looking forward to hearing from you.
God Bless you for your kindness and help.

Sharon Rader


"Dachshunds leave footprints of love on your heart"

Dr Lee
March 23rd, 2008, 05:31 PM
I will email you directly.

beatricej
September 13th, 2008, 07:52 AM
Hi,
my 17 months old choc. lab. has been diagnosed with polycythemia vera a month ago(we are still waiting for some EPO test results to confirm this diagnosis) .
So far she had 3 phlebotomies (one today) and she started taking hydossyurea one week ago (1 capsule every second day). Everything started with a lameness on her foreleg, followed by lethargy, diffculties in breathing and walking properly, tiredeness.. After her second phlebothomy she started to improve a bit, she was more energetic and she looked happier.. but at the same time her difficulties in breathing became worst and worst. Today I got very scared because it seemed like she couldnt breath at all. I went to the vet which did another phlebotomy and increased hydrossyurea to one a day for a week. I am very worried since I believe the vet underestimated this lung problem she obviously has.
He told me it could take even 2 months before her conditions might improve and there is not much to do to make her feel better.
I was hoping to find some second opinions or previous experiences in here..
thank you

DOXIELOVER5
September 13th, 2008, 02:36 PM
Hi Beactrice.

We live in a rural area and the vets here were not sure about the problem.Due to Fridays age, and much research we are doing aspirin, Lasix, and pepcid. Everything has improved. :thumbs up
It is still not great but better. He is living a normal life and happy and no discomfort. He also has COPD. I posted about that and got no answers. When things get bad with the breathing he goes in for a injection. At this time I'm striving to make him comfortable, Friday is the type of dog that would not have did well with the type of treatment your furkid is receiving. I also felt there were too many things that could have gone wrong with him having it done.
Good luck to you and your baby. Hope he gets better.

Sharon

Clark171
October 9th, 2008, 06:20 PM
Our thanks too, Dr. Lee. Our beagle has just been diagnosed (PCV 77%). We contacted Urs Giger since the genetic testing laboratory he runs at the University of Penn used to conduct Erythropoietin (Epo) testing for dogs but has since discontinued doing it.

His discussion of the differential diagnosis for erythrocytosis was very informative.

Are you aware of any labs doing Epo testing for dogs?

Thanks again for your post.

Charlie