also see Immune mediated hemolytic anemia
also see IMHA
also see Bloodwork
also see blood disorders
also see immune disorders
also see vonWillebrands
Immune Mediated Thrombocytopenia, IMHA and Evans syndrome . - Golden Retriever
Question: STUMPED OWNER & VET (I think)
In late November I took my dog to the vet because I had noticed blood in his urine. Upon examining Indy (male, intact, 4 year old, Golden Retriever) the doctor mentioned his prostate was a little larger than normal but that this was nothing to be concerned about. An ultra-sound was performed to rule out bladder/kidney stones and to also take a look at his prostate. Immediately after the ultrasound was performed, Indy began bruising severely. Blood was drawn along with urine. Indy was diagnosed with Immune Mediated Thrombocytapenia. He was hospitalized for 5 days and treated with a cocktail of drugs (doxycycline, prednisone, sucralfate, & azithioprine among them) at that time his platelet count was around 3,000 and red cell count was a little on the low end, all other blood work and urine samples came back normal. After he got out of the hospital the doctor had him on the following medicines:
Weeks 1 & 2 80mg prednisone twice daily 10mg azithiprine once daily 100mg doxycycline twice daily ? mg sucralfate three times daily
Week 3 60mg prednisone twice daily 10mg azithiprine once every other day pepcid once daily
Over the three week period, Indy's platelet counts rose from 3,000 to 274,000. At the end of week three Indy became lethargic and began vomiting , I immediately took him back to the doctor. He was admitted back into the hospital because he was severely anemic and his white cell count was around 52,000. Apparently the azithioprine was causing toxicity of the liver (this is a guess by the doctor), I am sure the extreme doses of prednisone did not help. Because he was not recovering, the doctor removed him from all medications for two days. He began recovering instantly, his blood work showed all levels as normal (platelets at 474,000). He was sent home with 100mg of Baytril twice daily for two weeks and 5mg of prednisone daily. After a week of being home Indy's white cell count was at 31,000. After the full course of baytril had been given his white cell count went to 41,000. Currently we are in the process of weaning Indy off the prednisone, the doctor suspects this could be causing his white cell counts to be elevated.
1- What does an elevated white cell count mean and what is the normal range?
2- Do you know of another diagnosis for what might be going on? Could it be bone cancer, hepatitis, liver disease, liver cancer, or prostrate cancer? And would the blood work (CBC) show anything to reflect so?
3- Could the thrombocytapenia be symptom of something else going on? Why was recovery for Indy's thrombocytapenia so quick?
4- I read one subscribers' question about copper toxicity? I have copper pipes in my house, because of Indy's extreme thirst he consumed 1-3 gallons of water daily while he was on the prednisone. Is there a possibility he could have copper toxicity? Would this be reflected in the blood work?
5- I have learned an immense amount from browsing your dog library. This really is a wonderful service you provide! Any advice, recommendations, or help you could provide me with would be greatly appreciated.
Thank you. Adrienne
High white blood cell counts occur because the immune system is stimulated in some way. Usually this is infection or inflammation. In the case of immune mediated hemolytic anemia (IMHA) and immune mediated thrombocytopenia (ITP), the stimulation is an abnormal recognition of the red blood cells or platelets by the body, leading to an attack on them by the white blood cell system. The normal white blood cell count for a dog is around 6500 to 16,500 wbcs/ul of blood. This varies some from laboratory to laboratory but usually not too much.
In a case in which platelets were low, in combination with a high white blood cell count and anemia, I would be concerned about the possibility of Evan's syndrome, which is ITP and IMHA occurring at the same time. This can be very confusing to diagnose, because there are inconsistent signs for either condition and they do not occur together frequently, so the possibility is sometimes overlooked.
IMHA usually causes high white blood cell counts, in the range that you are seeing with Indy and it causes anemia and usually icterus (yellow discoloration of the skin or whites of the eyes). ITP causes the bruising problems frequently, anemia much less commonly and usually there is not a high elevation in white blood cell counts associated with this condition. So you are seeing signs of both disorders and therefore, Evan's syndrome has to be considered. The treatment for Evan's syndrome is basically the same as the treatment for either ITP or IMHA occurring alone, though, so there is usually a response to treatment since one or the other of the conditions is usually recognized.
There are some causes of immune mediated hemolytic anemia in which platelet numbers drop in conjunction with the IMHA. The most severe of these are metastatic cancers and disseminated intravascular coagulation (DIC). Most dogs with DIC are in severe trouble and it is pretty likely that you can rule this diagnosis out based on Indy's response to treatment. The last condition that I know of that is linked reasonably often with both IMHA and low platelet numbers is systemic lupus erythematosus. It may be a good idea to consider this possibility if other signs develop, such as joint soreness or skin disease -- or just if there is not a time when you can wean Indy off the medications.
I think that your vet is considering the possibility of tick borne disease, such as ehrlichiosis, based on the use of doxycycline. This is a reasonable precaution.
Thrombocytopenia often responds to treatment very rapidly. We see this condition most commonly as a drug reaction, usually to sulfa-trimethoprim combination antibiotic use and the combination of medications and withdrawal of the medication usually stops the thrombocytopenia pretty quickly.
Immune mediated hemolytic anemia responds to treatment a little more slowly, usually taking a week or so to show progress in red blood cell counts. IMHA can be diagnosed in some instances by examination of the blood for auto-agglutination or abnormal cell types (spherocytes) that are typical for the condition.
Copper toxicity usually occurs in dogs that just don't have the ability to process copper properly in the liver and so it builds up there over long times. It is not a common problem and not at all likely from copper pipes in the house or environmental exposure.
The usual dosage of prednisone for these conditions is 2mg/kg of body weight per day ( 1 mg per pound of body weight per day).
I hope that things are better at this time. The progress during the time your note covered is very encouraging.
Mike Richards, DVM 1/24/2001
Question: Dr. Mike:
I have a few questions about Thrombocypenia in the dog. My two year old German Shepherd was diagnosed a few months ago with it. They have not been able to find a cause. His Platelet count (on medication) went as high as 250,000 to 305,000. We had started cutting back on the Pred and his Platelet count began to slowly drop until it reached 87,000. Then we upped the dose to 30 mg. (we just did another blood test and I am hoping the count is up again). Can you tell me, is this normal? The ups and downs. One other thing, my dog is a high drive dog with lots of energy. My vet says that working him is out of the question when his Platelets are down (he is training in Schutzhund and does alot of bite work as well as ball work) but he can't tell me why? Should I be concerned about exercising him and what will it do? Also, the only test that we haven't done on the dog yet is a bone marrow test. Is it worth it to do this? What will they be looking for and if they find something is the treatment any different than what we are already doing? (My dog is on 30 mg. pred every day and 75mg of Immuran every other day). I just need to know if there is any hope for my dog to see recovery or remission. Are there any resources that I can access to read more about this disease so I know what to expect. This is the first case of Thrombo that my vet has treated and he does not seem to have many answers. Mainly what I get from him is "I don't know". The blood tests are costing me a fortune and I at least would like to know more about the disease and what can happen. Can you give me any insight? Thanks.
It is not unusual for platelet numbers to vary significantly from one blood sample to another, even when the numbers are normal. The variance can be in the hundreds of thousands of platelets, since the numbers of platelets in the blood is so high. It is also not unusual for the trend in platelet numbers to vary during treatment, especially when an effort is made to withdraw immunosuppressive medications such as prednisone or azathioprine (Imuran Rx).
According to a good chapter on infectious and immune-mediated thrombocytopenia by Carl Grindem in Kirk's Current Veterinary Therapy XIII, platelet numbers below 200,000 platelets/ul are indicative of thrombocytopenia, although dogs do not usually have problems unless platelet numbers fall below 100,000 platelets/ul.
I do not know of any reason not to work your dog when the platelet numbers are controlled through therapy, or after recovery from this disorder. I would worry about the possibility of contracting an infectious disease when your dog is in a stressful situation around other dogs, though. It usually takes immunosuppressive dosages of prednisone or other medications to control immune mediated thrombocytopenia and this increases the risk of contracting diseases. I guess there would be some worry about bleeding associated heavy training activities, such as bite work. This should be a fairly low risk with platelet counts over 75,000/ul but it may be concerning your vet, as well. Environmental stress is considered to be a factor in relapses in cases of thrombocytopenia, but it is hard to know if activities your dog is used to, and probably enjoys, are stressful or helpful.
A bone marrow aspirate and core biopsy sample are considered to be necessary in the diagnosis of platelet disorders that are not responsive to therapy or which become very chronic. Bleeding is not normally a problem even when thrombocytopenia is present, unless platelet numbers are less than 20,000/ul. Blood clotting tests such as prothrombin time (PT), fibrinogen, activated partial thromboplastin time (APTT) and activated clotting time (ACT) should be run to make sure that the platelet problem is not part of another blood clotting disorder.
The reason for doing bone marrow examinations is to determine if there are adequate numbers of the megakaryocytes, the cells in the bone marrow that produce platelets. If there are high numbers of these cells in the bone marrow but low numbers of platelets in the circulation, then the most likely problem is that they are being destroyed after they are produced. If there are not enough megakaryocytes in the bone marrow to produce adequate numbers of platelets, then it is necessary to think about other problems, such as an infectious disease or toxin that is destroying the platelet producing cells. There is a variation of immune mediated thrombocytopenia (ITP) in which antibodies are produced against the megakaryocytes instead of the platelets but it is rare. So if there are few megakaryocytes in the bone marrow sample, there is probably something other than ITP going on and if there are large numbers of megakaryocytes it is more likely that ITP is present.
The prognosis for immune mediated thrombocytopenia is generally good and most dogs recover from the disease. A few dogs require lifelong therapy and some dogs (as many as 20$%) do not respond to therapy well and die from complications of this disorder, such as intestinal or pulmonary hemorrhage. It is a little scary when tapering prednisone and waiting to see if the platelet levels will drop. It is reasonable to do this. We usually treat for two to three weeks and then start to taper off prednisone, shooting for every other day use and then tapering off the medication after one to two months. If this doesn't work, we would probably consider doing a splenectomy to see if that would provide additional relief from the thrombocytopenia but I can't remember having to do that.
There are a number of known causes of infectious thrombocytopenia. The most common is ehrlichiosis, probably. Rocky Mountain spotted fever, viral illnesses, generalized bacterial infections, leptospirosis, heartworm disease, babesiosis, bartonellosis (cats) and some of the fungal illnesses can lead to thrombocytopenia. Immune mediated thrombocytopenia is associated with some medications, especially sulfa/trimethoprim antibiotics. Other medications and treatments may suppress platelets without inducing immune suppression, such as chemotherapeutic agents. Short periods of thrombocytopenia may occur after vaccinations with modified-live viruses.
This can be an expensive disorder to work up properly, because of the great number of possible causes, the need for tests like bone marrow cytology and the need to monitor therapy carefully. This is balanced by the good overall success rate for treatment, especially when a cause can be identified and appropriately treated.
Hope this helps.
Mike Richards, DVM 9/24/2000
Question: Dr. Mike, I have read the letters and responses re Thrombocytopenia, but wanted to get your opinion re our dog's future. He is a 7 year old Doberman; had to have emergency surgery and a transfusion as a puppy when he was neutered; diagnosed with polyarthritis and colitis at about 14 months and with hypothyroidism at about 6.5 years. He was hemmoraghing a couple of months ago and was diagnosed with Thrombo.... Tests were neg. for Ehrlichia. He has been on Prednisone and Doxycycline and was responding very well, platelet count went from "7" to "276" within about 4-6 weeks of beginning treatment; meds were reduced (10 mg. Pred/day). Currently his platelet count is dropping. First time dropped to "176", now "161". They tried putting him back on Doxy, now we are bumping his Prednisone back up to 20 mg. (2 X 10) per day and dropping the Doxy. Understandably (to me) our vet is offering no prognosis for his future at this point; please give me your opinion. Pat
Answer: Pat- Platelet counts are notoriously variable in dogs. I try not to get excited about changes in numbers, as long as there are adequate numbers of platelets. We use 100,000 (usually denoted as 100 in a sort of accepted shorthand for these numbers) as our point for thinking about the possibility of problems. In dobermans you have to worry about platelet number and platelet function, though. Von Willebrand's disease in this breed can cause a dog with normal platelet numbers to have bleeding tendencies, since the platelets don't work properly.
I consider 176,000 and 161,000 platelets to be essentially the same number and do not consider a drop from 200,000 to 161,000 to be significant, except that I would want to recheck the numbers in a few days to be sure there wasn't a more severe downward trend. Given your dog's history, though, I can see why your vet went back to the doxycycline and increased the prednisone dosage.
In general, the prognosis for immune mediated thrombocytopenia is pretty good. If you haven't done it yet, getting a blood test to determine if von Willebrand's disease is a problem, too, would be a good idea. There is a gene based test for this now and also serum testing, which has been the standard prior to the genetic testing.
Hope this helps. I am pretty sure the URL for the genetic testing lab is on the web site but if you can't find it, I will be glad to send it.
Mike Richards, DVM 4/29/2000
Question: Dear Dr. Mike,
I have found your web site to be very informative and have recently become a subscriber. I am interested to hear your opinion on the situation we've been experiencing with Chelsea, our two year old bichon.
In July of 1999, at the age of 1 year and 11 months, she was diagnosed with localized Demodex. At that time she was also experiencing a pretty severe ear infection (she has had ear infections her whole life but this one was particularly bad).. She was prescribed a variety of topical medications as well as Ivramectum (?). After about one month of the veterinarian telling us to "just be patient" we took her to a veterinary dermatologist. She confirmed the Demodex diagnosis but adjusted the medications to include Cefa-tabs. Two days later we noticed a rash on her stomach and our veterinarian had us bring Chelsea in immediately to confirm that the rash was, indeed, patichae. The technician drew a blood sample from Chelsea's neck and it swelled to the size of an orange which the vet told us indicated thrombocytopenia and he immediately gave her a shot of steroids. It turns out that her platelet level was 18,000. This was in late September.
Chelsea has always been the most energetic, playful, happy dog and since this all started has been mopey and sad and not interested at all in playing with people or our younger dog, Abbey. Upon being diagnosed with thrombocytopenia she went through a multitude of tests: three lumps were aspirated and found to be benign, an abdominal CT scan was performed which showed nothing, a bone marrow aspirate was taken (she was producing an abundance of megakarocytes), lupus was ruled out and a tick assay came back negative. Her regular veterinarian as well as her internal medicine specialist initially thought the Cefa-tabs may have caused what they have concluded is auto-immune thrombocytopenia but now have come to the conclusion that it is actually idiopathic.
She was prescribed Prednisolone and eventually Imuran was added to her regimen. She is currently taking 20mg of Prednisolone and 12.5mg of Imuran daily. Her platelet level has gone from as low as 3,000, whereupon she was sent down to the Veterinary Clinic at The University of Illinois for a week in ICU, to this past week where her platelets reached a level of 264,000. For the last two months her platelet count has bounced around all over the place. In addition, last week she was bleeding vaginally for two days. I should also add that since the Prednisolone and Imuran were added to her daily regimen the Demodex and the ear infection have completely disappeared.
I have a few major concerns which I hope that you can address: 1. Can you think of anything else we should rule out before settling on a diagnosis of idiopathic auto-immune mediated thrombocytopenia since it appears something is causing her platelet count to jump around? 2. How long is it safe for Chelsea to be on such a high level of drugs that can cause bone marrow supression and/or cancer? 3. Have you ever seen a case where a dog's immune system appears both overactive (auto-immune mediated thrombocytopenia) and underactive (Demodex/ear infection) simultaneously?
I know that I've given you a lot of information but I would appreciate your opinions.
Thank you, Donna
The disorders that most commonly induce thrombocytopenia (platelet deficiency) are drug reactions (cephalosporins can cause these), cancers, infectious illnesses --- especially ehrlichiosis , systemic lupus erythematosus, rheumatoid arthritis and von Willebrand's disease. It is important to consider all of these possibilities in a dog thrombocytopenia.
If no primary cause can be identified then the condition is referred to as idiopathic thrombocytopenia (ITP). Since this diagnosis is made by ruling out disorders that are sometimes hard to find, it is always suspect. Rechecks of previous tests are often important as diseases or disorders that lead to thrombocytopenia are sometimes easier to find at one time than another.
When drugs cause thrombocytopenia it will usually resolve as the drug is withdrawn, so continued problems is very suggestive that the problem is not drug related in Chelsea's case.
ITP is more common in females than in males. I am not sure why.
The immune deficiency that leads to demodecosis is very specific and it doesn't surprise me that seemingly opposite problems are occurring at the same time --- with an overactive immune system in one area but deficient in another.
It does surprise me that the demodecosis did not get a lot worse when corticosteroids and azathioprine were administered. This would be a common complication of using these medications. Localized demodex sometimes occurs as the result of significant immune stress, though. The lateness of the diagnosis makes this seem like it might be a problem --- most dogs with demodecosis have symptoms prior to one year of age. Since a lot of the problems that lead to ITP are stresses to the immune system, such as viral infections or ehrlichiosis (a blood parasite), it seems even more important to me to search for a primary cause.
I am sure that the possibilities listed above were considered and ruled out, as well as possible, by the veterinarians who have examined Chelsea since it seems like she has received good care. It may be worthwhile to recheck for some of the problems.
One other thing to consider is that platelet counts often vary a lot from one blood sample to another. We have seen the counts change by over 200,000 platelets in one day. In general, a platelet count of about 70,000 is considered to be adequate to prohibit bleeding, as long as the platelets are active. Platelet counts as high as 600,000 fall within the normal range, so there is a lot of room for variability. Obviously, you need to keep monitoring the counts until they consistently stay in a normal range without medication (if it is possible to get to that point) but it will vary a lot from sample to sample.
It is best if it is possible to use only one immunosuppressive agent and it is best if it is possible to eventually wean a dog off the medications. Not having platelets is a lot more risky than the side effects of the medications, so even if they do have to be used very long term to control ITP, they are better than the alternative. But once in a while the dosage should be reduced just to see if it is possible to stop the medications. This has to be done carefully and under the supervision of your vet. Eventually most dogs can be weaned off the immunosuppressive medications successfully.
Good luck with this.
Mike Richards, DVM 1/5/2000
Question: Hi, i have a very strange situation going on and was hoping for some advice:
my shepherd mix, about 6, has not been himself lately. i'd say that this occurred about a year ago, too, and now just recently. he presents with
several of the clinical signs mentioned for ehrlichiosis: really sore neck/shoulders facial spasms/tremors loss of appetite lethargic seems depressed.
we took him to the vet and they said he must have just played too roughly. i asked for a blood test but they said it would just be a waste of money.
a week later, the tremors (first and only time) happened after one low dose aspirin was given (80 mg).
blood tests confirmed thrombocytopenia: a platelet count of 22,000
so...80 mg of pred were given, xrays taken just in case (slightly enlarged spleen), neck seemed fine.
next day, diet of only chicken and rice...pred (40 mg twice a day), and rest. that night he was up all night vomiting first food, then blood, then very dark tarry and red bloody diarhea...it was awful. the next day it was a full day of i.v. fluids, plus injectable steroids (since his stomach was so messed up), and vincristine.
the platelet count goes as follows: 1st day of problems: 22,000 2nd day: 9,000 began pred: 40 mg. twice a day 3rd day: 10,000 (gave vincristine after the blood draw this day) 4th day: 22,000 5th day...no blood taken, waiting until day 7 to give him a break.
i'm terrified of chemo drugs. my other shepherd mix (also 5) died 2 years ago from systemic lupus erythematosus with lymphosarcoma at the end. we did treat him for ehrlichiosis (negative titer) with doxycycline...no result after 3 weeks.
it's so scary to have nick, this current dog, showing some of the same "immune" disfunctions as our other boy, max, had 2 years ago.
i called the vet yesterday to ask if there was anyway it could be ehrlichiosis. i assume it would be e. platus since his platelets are affected. since his neutrophils are affected (very high) (his wbc are at 38,000) she wanted to put him on amoxy, but after hearing my concerns she said "let's do doxy" which made me happy. i am going to ask for a titer to be run for ehrlichia (including e. platys) on monday.
twice i've read that steroids are a no no for ehrlichiosis patients...why?
sorry this is so long but i'm very nervous. nick is now off his food (i can get him to eat a spoonful every few hours only), which wouldn't be so bad but i am supposed to give him his prednisone now and i'm nervous to do it without food and with the possibility that he has ehrlichiosis instead of just i.t.p.
i specifically wonder if it is okay to let him skip his prednisone today (i can't get hold of my vet because it's sunday), especially because he has diarhea (though it is normal colored, but had one speck of blood in it just now) and i'm worried about starting another bout of vomiting/diarhea and loss of blood! he's only been on the pred for 4 days...i know that you should never stop pred suddenly, but i really would like to give his g.i. tract a rest and wait for the ehrlichia results as well!
any thoughts you have would be so appreciated. thank you! sue
There are several causes of decreased platelets, but ehrlichiosis and immune mediated thrombocytopenia are probably the two most common. In general, it is safe to treat with doxycycline, just in case ehrlichia is present and prednisone or another corticosteroid, to decrease the immune response that is wiping out the platelets, regardless of the cause.
If there is not a good response to this therapy, then more intense diagnostic work may be necessary. Bone marrow aspirate and exam may be the best next step, because some forms of cancer will suppress platelets (but usually more than just this cell line in the bone marrow is suppressed).
German shepherds are also prone to immune mediated hemolytic anemia and sometimes the platelet count will drop with this condition, too. Hemophilia also occurs in shepherds and if there is a lot of bleeding it is possible that the platelets are just being used up in an effort to control the hemorrhage. I think that it would be unusual for you not to have seen clinical signs prior to six years of age if hemophilia is present, though.
We have seen bleeding and marked decreases in platelets in dogs with hemangiosarcoma tumors and these also seem to be a common problem in middle aged and older shepherds.
The initial treatment for all of these conditions is pretty similar, as long as you are using an antibiotic for ehrlichiosis, so it is OK if diagnosis takes a few days, usually.
If the bleeding continues to be a problem it might be a good idea to think about asking for referral to Colorado State or a referral center that has blood available for transfusions and where advanced diagnostic testing is available.
I am not comfortable going to alternate day (every 48 hour) prednisone administration until the platelet count is rising well and usually won't do this until the platelet count is over 100,000.
I know that this is a tough time. Keep in contact with your vet and if your vet suggests referral for diagnostics or therapeutics take the suggestion seriously.
Mike Richards, DVM 2/15/2000
Question: Dear Dr. Mike: You have responded to my questions before about my 7 year old female Springer Spaniel with thrombocytopenia who has been on Imuran 25mgm X 5 per week. My Vet has been lowering the dosage slowly (one dose per week) with monthly blood tests and we have been able to reduce the meds to 25 mgs X 2 per week. My dog has been having terrible skin reaction, which respond to antibiotics, then reoccur. I am most encouraged by this but have noticed an increase in her appetite. She lies by the frig constantly, and eats "diet dog food" with gusto! My vet does not know why this is happening. Could it be that she just feels better, or is something else going on? She looks great, just a little obese. Her gum color is pink, and there is no mottling of her skin. Do you think the disease is in remission, or has it burned out?
Any thoughts you might have would be most appreciated. Cherie
I have not seen increased appetite listed as a side effect of azathioprine (Imuran Rx) but it is my impression from our clinic's experience that this sometimes occurs and I have talked with another vet who had a similar impression. That isn't a very scientific answer, since neither of us really kept track of the cases nor tried to rule out other causes. But it was our impression. In our clinic's case, we do not use azathioprine alone, very often. We usually use it combination with prednisone. Since increased appetite is definitely a problem with prednisone, our impression may be influenced by that.
Dogs who go through periods of starvation, for whatever reason, sometimes lose the ability to control their appetites in the future. They just seem to override whatever it is that causes normal animals to stop eating. If your springer got really sick and wouldn't eat during the initial phases of this disease, that might also be a contributing factor.
Most of the dogs we have seen with idiopathic or immune mediated thrombocytopenia have eventually recovered completely and life long immunosuppression has not been necessary. So I do think there is a strong possibility that your dog will also be able to be weaned off the medications completely at some point. Even though we worry about future remissions or recurrences and watch these dogs carefully, most of the time the disorder does not recur.
I would be suspicious that the skin disease you are seeing is partially the result of immune suppression from the azathioprine and partially the result of a natural tendency to develop skin disease, since it responds to antibiotics well. If it were a drug reaction it seems like it would be less likely to respond to antibiotics. Hopefully, as you are able to wean your dog off the azathioprine the skin disease will clear up. If not, you may find that you have to use antibiotics on a regular or even a continuous basis.
I hope you are nearing the end of this problem.
Mike Richards, DVM 2/20/2000
Question: Dear Dr. Mike, My 6 year old female Springer Spaniel has had thrombocytopenia since age 2. She was worked up at Davis, Ca (platelet count below l0,000) and has been on Imuran 25 mgm 5 times a week. Her platelet count on this dose has been steady at about l25,000-200,000. She has begun to have many skin infections and we are now trying to lower her dose. Do you have any thoughts on this condition? She does not tolerate Prednisone well. I am an RN and want to know as much about this disease as possible. Many thanks, C.I.
We periodically try to decrease the dosage of prednisone or other immunosuppressive agents when dealing with immune-mediated thrombocytopenia and so I think that doing that is a good idea. If the count remains stable then we monitor on a periodic basis, usually for six months to a year, and then we just try to remember to keep a high degree of suspicion for the condition in the future in that patient.
If decreasing the dosage of prednisone or azathioprin results in the return of thrombocytopenia to threatening levels, then we usually just continue with the medications.
I was at a seminar on hematology several years ago given by Dr. Feldman at the Virginia-Maryland Regional College of Veterinary Medicine and he said that he was following several patients who had low platelet counts, but no bleeding episodes and who were not being treated for the condition, and had been following their progress for several years. I believe that he was referring to platelet counts of less than 75,000/ul and remember him mentioning one dog with a very low count (25,000/ul sticks in my memory) that had not had any problems. His point was that low platelet numbers alone may not require treatment - that monitoring for bleeding problems may be all that is necessary. Of course, picking the patients to watch rather than treat has to be done carefully. Mucosal bleeding time testing or other methods of testing for a tendency to actually have bleeding problems is necessary to decide what steps to take.
In general, around 75,000 platelets/ul is usually adequate, if the platelets are functional, to control bleeding satisfactorily. In some cases there is not only a platelet deficiency but also a decrease in platelet function, which causes further problems even with platelet numbers that are in the adequate range. At platelet levels below 50,000 platelets/ul there is a chance of gastrointestinal bleeding and at levels below 25,000 platelets/ul obvious bleeding disorders (blood visible inside the eye, blood in tears or saliva, etc) is likely to occur.
It is likely that at some point the possibility of a blood parasite has been addressed but a possible cause of thrombocytopenia is ehrlichiosis and it is usually responsive to doxycycline. Trying the antibiotic for three weeks is reasonable to rule out this problem.
Other medications sometimes suggested for thrombocytopenia include vincristine and cyclosporin. I think vincristine is usually used in short term crises and cyclosporin for long term use. Cyclosporin could easily produce the same kinds of problems you are already seeing with azathioprin, though.
Splenectomy is another option. There are dogs who respond really well to splenectomy to control thrombocytopenia (just in case, splenectomy is removal of the spleen). The spleen is the organ that removes damaged platelets from the bloodstream and sometimes it works too hard, removing good ones, too. I don't know of a good way to tell in advance if splenectomy will work and it does involve both anesthetic and surgical risk, although these risks are great. It is a judgment call, but if you are having problems with immunosupression due to the medications necessary to control thrombocytopenia it could eliminate the need to use them.
There is no clear path to successful treatment of thrombocytopenia. It is partially a trial and error process to find what works. I hope that you are able to do this. I also hope that the problem has stabilized and further treatment is not necessary, anyway!
Mike Richards, DVM 11/12/99
Q: Hi, I need help I have a 2 year old Female German Shepherd. My dog delivered a litter of 4 pups on June 9, on June 10 I had to take her into the vet she was still having contractions the vet said her uterus was to large so they gave her oxytocin, and sent her home. She had a X-ray no other pups or placenta remained. On June 17 she began to bleed from her nose and mouth.Also vaginally. They tested her for autoimmune, negative and then for tick borne diseases also negative. She had a platelet count of 0. We eventually took her to a specialist who found she had a infection in her uterus.They spayed her and cleaned everything out.She received a blood transfusion right before surgery. Surgery went well. Her platelet count did not rise at all. On June 26, they started her on Danazol. Her count went from 0 to 1,000 on 6/27.On 6/28 her count went to 13,000.Now today it is 0 (6/29).They are going to try a horse serum? Please if you have any advice please help us she is bleeding from her nose and vaginally again.Please help.
An emergency option for this situation is fresh frozen plasma, fresh plasma or whole blood. Most veterinary emergency hospitals have blood products available. The platelets do not last long from transfusions but they can give you time to get other medications to work.
Our first line of treatment for this condition is to use immunosuppressive doses of prednisone. I can't tell from your note if that has been done. I can see a worry over doing this in the face of an infection but if the uterus was removed and it has been more than a day or so since surgery (time to allow initial healing) then I would use corticosteroids without too much hesitation.
Vincristine (a chemotherapy drug) is used fairly commonly for immune mediated thrombocytopenia (ITP) when other medications aren't causing rises in the platelet count. The dose, according to Dr. Plumb's formulary, is 0.010 - 0.025 mg/kg IV at minimum of 7-10 day intervals. Azathioprine (Imuran Rx) is also commonly added to prednisone usage when platelet levels aren't rising. Cyclophosphamide, another chemotherapeutic agent, can also be helpful. Danazol has been reported to be helpful in some literature accounts and not so helpful in others -- which is true of ALL of the drugs used for this condition, so switching medications is commonly done when things aren't going well.
Thrombocytopenia usually occurs for a reason. The tick disease panel was a good start on figuring out why. Review the use of antibiotics. Sulfa/trimethoprim combinations will sometimes cause ITP and are commonly used in infections in veterinary medicine. Infections are sometimes sufficient to cause ITP, too. Just think about anything that happened during this time, with your vet's help, to rule out possible causes that might be treatable.
The platelet count is low enough to lead to overt bleeding but it is also important to keep on the lookout for other bleeding disorders that might occur secondary to the ITP, such as disseminated intravascular coagulation (DIC). Treat for this if there is any suspicion it is present because waiting to be sure is often waiting too long.
Good luck with this. Ask your vets about prednisone or other corticosteroids if they are not being used. If their rationale for not using them is worry over infection or surgical healing, consider the strong possibility of death if the low platelet count persists and factor that into the risk vs. benefit equation. Your vets are in a better position to make that judgment but the situation appears to be getting grave and that is time to make more risky treatment attempts, sometimes.
Mike Richards, DVM 7/1/99
Q: Dear Dr. Mike, I am writing to you in regards to my 2 year old spayed Golden Retriever, Garli, that has been diagnosed with canine thrombocytopenic idiopathic purpura about 5 mon. ago and was career changed from Guide Dogs for the Blind due to this problem. Her platelet count when GDB went to spay her was 5,000, but now is slowly going up as she is at about 110,000 as of Jan. blood count. She is currently receiving 2 mg. of Prednisone every other day and my vet hopes in time to decrease this, but wants to wait about 6 mon and let her get stablized. At the recommendation of GDB we had tried to half her dosage 2 weeks after her return here, but her platelet count really dropped so we had to put her back on the 2mg. of Prednisone. I was wondering what long term effects this will have on her? Life expectancy? Health problems? Special problems or concerns? Will she ever be able to discontinue the Prednisone? Any case histories that will help me to understand this problem and to give her the best care I can ? Is this a genetic disorder? One of her littermates has graduated and is a working Guide Dog. Are there any books or articles pertaining to this disorder? I just read an article in Vet. Med./Sept.96 on it. We dearly love this dog and want to do what's in her best interest and well being! Thanks for taking your time to read this and respond to an anxious owner. Goldenly,
A: Thrombocytopenic purpura can occur for no apparent reason and this is known as idiopathic thrombocytopenic purpura (ITP). It can also occur for a number of reasons such as drug reactions, severe infections, toxins, cancer and disorders of platelet production that do not directly involve the platelets. These things are known as secondary thrombocytopenic purpura (I have never seen this called STP).
Personally, for no reason other than experience, I think that most cases of platelet problems are secondary to other things. In our practice, the single most common cause of this condition has been the use of sulfa/trimethoprim antibiotics but other people may have different experiences. The good thing about this situation is that almost all dogs will recover with withdrawal of the offending medication and treatment with corticosteroids like prednisone for several weeks to several months. If the primary cause is not easily removed (like some cancers and the autoimmune disorders) then treatment is much more difficult. If this is an idiopathic condition, it is hard to predict how long it will be necessary to use corticosteroids, but it is often possible to wean a dog off of the prednisone over time. Other times, it is necessary to continue the medications lifelong but they can usually be given on an every other day or longer interval basis. If this can be done, long-term use is reasonably safe. Two milligrams of prednisone is a very low dose for a golden retriever. I suspect you might be giving 20mg every other day. If the first number is right, there shouldn't be any problem with long term complications and usually not much with the higher dose.
The article in Veterinary Medicine (Sept 96) is a pretty good review of this condition, if I remember right. As mentioned in the article, the real difficulty in diagnosing and treating this condition is eliminating all the possible secondary causes, since there are so many.
There are some inherited causes of thrombocytopenia like thromboasthenia in otterhounds. I think that I talian greyhounds and basset hounds also have an inherited platelet disorder. There may be some other breeds with inherited disorders but those are the only ones I know of.
Hope this helps some. Mike Richards, DVM
Q: We are hopefully coming out of a very difficult siege with our miniature 8 year old poodle. About a month ago, red spots suddenly appeared all over her underside - they were small hemorrhages. Her platelet count was down to 11,000 . . . we were looking at a life-threatening problem - probably blood or liver connected.
Well, her platelet count is up to 440,000 this week, and we are tapering off on the cortisone and antibiotic medication - hopefully her count will stay high and she will be with us for many more years.
Like everyone else in this type of situation, we want to know what caused this problem . . . especially since it seemed to manifest itself almost overnight. Our vet offered very few possibilities.
We are curious to know if having our pup on Lufenuron program could have had some effect - the literature with the medication tells us that the drug "changes" something in the blood . . . and that's when the bells and whistles went off! Do you know of any research on side effects of Luferuron? Is there somewhere that I could call or fax to put my mind at ease? Is there an searchable internet s ource for vet blood/liver problems? Source to check out vet prescriptions for side effects?
A: I am not sure why your vet is suspicious of liver problems in this case. It is entirely possible that there is a good reason, but I am not sure what it might be.
Just on the facts presented in your email, I'd be most suspicious of a platelet disorder, either immune mediated or idiopathic (occurring for unidentifiable reasons). There is also the possibility of some sort of disease suppressing platelet formation or causing destruction of the platelets. Ehrlichiosis can do this and sometimes cancers will also lead to early destruction of platelets. A decrease in platelet numbers is referred to as thrombocytopenia.
Immune mediated thrombocytopenia (ITP) can occur due to drug reactions. I am pretty sure that the most common cause of this in veterinary practice is the use of sulfa-trimethoprim antibiotics such as Tribrissen (Rx) and Ditrim (Rx). It can also occur with phenylbutazone and with estrogen therapy. There are other drugs known to cause ITP but those are the most common ones. It also occurs due to bacterial or viral infections, cancer and possibly even allergies. It almost always responds to treatment of the underlying condition (if possible) or withdrawal of the medication causing problems along with corticosteroid therapy. It is OK to taper off the dosage of prednisone once the platelet count returns to normal ranges. Usually it is possible to do this successfully. Some dogs require long term therapy with corticosteroids. In others, it is not possible to control the initiating factors (especially cancers) and therapy may not work long-term. In really unresponsive cases, stronger immunosuppressants may be necessary. Some dogs do fail to respond to therapy.
To the best of my knowledge, this has not been reported as an effect of lufenuron (Program Rx). Ciba-Geigy (now Novartis) has a web site and your vet can call the technical support veterinarians for advice, as well. I think it is almost always worthwhile to report possible problems to the company making a product. After all, if no one does, how would anyone know a problem really occurred? Just remember that it is probably more likely the use of lufenuron and the ITP are unrelated.
Think back over the period just before your dog showed signs of problems and try to remember any medications, vaccinations, disease symptoms or other clues that might help your vet identify the cause of the problem. If there are no obvious causes, it is possible that your dog may have a primary case of thrombocytopenia. The treatment is pretty much the same and I think it has a pretty good prognosis.
I'd ask your vet to let you peruse his library for information. I let anyone read my books in my office. I won't lend them out because most people won't leave an essential body part as a deposit.
Hope this helps. Mike Richards, DVM
Q: Hi Dr. Mike; I have a 5 year old, male, Jack Russell Terrier who is unable to use his left hind leg. This all started about 9 months ago with a little limp and someday he didn't even favor the leg. This has steadily gotten worse and now I have to carry him outside to urinate. I have seen numerous vets. X-rays shows nothing, Myelogram shows nothing wrong. The only thing found were low platelets in blood, with a count of 52,000. Do you know of all the possible things that can cause low blood platelets? My vet is recommending a Tick/Rickettsial Panel and T4 testing. Are there any other diseases that can cause this and would this make him progressively worsen over a 9 month period? Any help or suggestions you can give would be appreciated. I want desperately to find out what is wrong with him and help him recover. He is my best friend and I hate to see him so unlike my fun, happy Jack Russell.
A: I thought about the lameness in one leg. I can't think of anything that seems likely to have been missed with the workup you describe. I did see in the last AVMA Journal that nerve root inflammation from spinal disc bulging was documented in a dog. That might not show up well on X-rays, even with a myelogram. Fibromyalgia type problems have been reported in dogs and they are probably pretty hard to document, too.We had a similar case in a Golden Retriever a couple of years ago that turned out to have lymphosarcoma in the bone prior to it spreading elsewhere but it was only lame for a month or so before it was pretty obvious what was wrong. For really hard cases, I think referral to a veterinary school is a pretty good course of action. They have a lot of different specialists in one place which can help with the process of identification in really odd problems. But you asked about differentials for low platelet numbers. The first one is that it could be normal for your dog. There are a number of references to dogs that have low platelet counts for no discernible reason that cause no discernible disease. Any platelet count under 100,000 has to be taken seriously but you can not just assume that there is a problem even with pretty low counts. Platelet number can be decreased due to destruction of the platelets by the immune system. This can occur for no reason (idiopathic immune mediated thrombocytopenia). It can also occur because of drug reactions (most commonly to sulfa/trimethoprim antibiotic combinations). Infectious diseases, most notably Ehrlichia canis, can also cause the immune system to destroy platelets. Lupus erythematosus and cancers can also initiate immune mediated destruction of platelets. Platelets can be destroyed without involvement of the immune system. Ehrlichia canis can directly cause the destruction of platelets and so can Rocky Mountain Spotted Fever. Platelet numbers often drop after vaccination with modified live vaccines in a transient reaction that seems to be a direct effect on the platelets. Severe vascular disorders or blood clotting disorders can lead to destruction of platelets. Sometimes, the platelets just aren't being produced by the bone marrow. This can be due to drug reactions and the worst offender here is probably estrogen. Phenylbutazone can cause suppression of platelet production as well. White blood cell cancers suppress the bone marrow but this is more common in cats. Other cancers seem to be able to do this at times as well.
Obviously, you can begin to see why your vet thinks that checking for rickettsial diseases is a good idea since it is usually lumped in with those diseases due to its transmission through ticks). The last thing that happens is normal production but increased usage of platelets leading to low platelet numbers. Dissemated intravascular coagulation (a severe blood clotting disorder) is an example of a situation in which this might occur. I think this happens with inappropriate blood transfusion (mismatched blood types) as well, but that might fall under the immune mediated category instead. Low thyroid levels have been associated with platelet inactivation problems. In this case, the platelet numbers are usually OK but they just don't work well. This occurs in von Willebrand's disease and many vets believe that giving thyroid hormone temporarily aids platelet function in dogs with this disease. I can't relate the two problems except through cancer and rickettsial disease or Ehrlichia, so it seems to me your vet is looking in the right direction. I suppose a drug reaction is possible but the only one that might cause both problems is trimethoprim/sulfa antibiotics and usually lameness associated with these antibiotics occurs in Dobermans and is reversible by stopping the antibiotic. I hope that you find an answer to this problem soon.
Mike Richards, DVMLast 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...