Immune-Mediated Thrombocytopenia (ITP) in Dogs

By Professor Michael Herrtage, James Warland, Andrew Kent & Julien Bazelle
The Queen's Veterinary School Hospital, University of Cambridge

Thrombocytes, or platelets, are the body's first defence against bleeding. They are tiny fragments of cells in the blood stream that are produced by the bone marrow. These fragments constantly patrol all of the vessels of the body in order to form a clot if any damage is caused to the vessel wall. In order to function normally, there are usually over 175,000,000 platelets in every millilitre of your dog's blood (up to 500,000,000/ml). The platelets form the first part of clot formation, but other factors are necessary to form an adequate clot if any damage occurs to the blood vessel.
If there are insufficient numbers of platelets present, the blood is not able to quickly form a normal clot. In a condition called immune mediated thrombocytopenia, the dog's own immune system attacks and destroys these platelets.
Although in most cases, thrombocytopenia is the only problem, in some cases ITP will be part of a wider autoimmune condition, with other organs affected. Examples of this include Evan's Syndrome, where the body attacks both the platelets and red blood cells (causing anaemia) or Systemic Lupus Erythematosus (SLE), where the body attacks multiple tissues.

Causes and Diagnostic Tests
ITP is caused by an autoimmune attack against the dog's own platelets, and usually the initial cause of this is unknown. It can be a primary problem or a secondary problem, triggered by other diseases. In the case of a dog with abnormal bleeding, your vet will need to run some tests to establish the cause. Blood tests will show a low platelet count (thrombocytopenia), however, it should be noted that ITP is not the only cause of thrombocytopenia.

Depending on your dog's previous medical history and their findings, your vet may choose to do further tests to look for an underlying cause of the thrombocytopenia. ITP can be caused by various infections, including viral and bacterial infections. The most important type of infection to cause thrombocytopenia in the UK is Ehrlichia, which is spread by ticks, and your vet will be able to test for this if infection is possible. Your vet may also perform other tests, such as X-rays and ultrasound of your dog to look for other causes of thrombocytopenia. Some drug treatments, particularly antibiotics and anti-inflammatory drugs, can cause thrombocytopenia. Unfortunately, ITP is diagnosed by ruling out other potential causes of low platelet numbers.
It is important to inform your vet if your dog has travelled outside the UK, as various infections that are not native to the UK can cause thrombocytopenia and it may be appropriate to test for these as well.

Clinical Signs
In dogs with ITP the most common clinical signs are associated with bleeding. Because clots are constantly being formed to prevent bleeding, even when no obvious trauma has occurred, dogs usually show signs of bleeding even without injuring themselves. Nosebleeds, bruising of the skin or gums, or petechiae (small red spotted rash caused by leaking capillaries) are common signs of ITP. Some dogs will have bleeding into their intestines, which cannot be seen initially, but leads to black, tar-like faeces (melaena). Some dogs will have more unusual sites of bleeding that can lead to other problems, such as bleeding in the brain or the eye.

dog1
Bleeding from the gums in an Irish Wolfhound with ITP

dog2
Small petechial haemorrhages in the skin of a Springer Spaniel with ITP

ITP Bruising on a Dachshund / Basset

Treatment
In ITP, the treatment is first aimed at decreasing the overactive immune system which causes this platelet reduction. The drugs used to decrease the overactivity of the immune system are called immunosuppressive drugs.

The main type of immunosuppressive drugs is corticosteroids, of which prednisolone remains the most frequently prescribed. Doses of prednisolone vary markedly between patients but high doses are generally used at the beginning of the treatment. Like any medication, prednisolone can be associated with side effects (e.g. increased drinking and urination, increased appetite, weakness, or rarely vomiting or diarrhoea). These side effects are by far less frequent than in human patients, allowing some canine patients to be treated only with prednisolone for a prolonged period.
If prednisolone alone does not control the clinical signs or if side effects are noticed, your own vet may also prescribe other immunosuppressive drugs (e.g. azathioprine, cyclosporine).
If the platelets level is critically low and bleeding had occurred, your veterinarian may suggest transfusion of fresh canine blood or other blood components. As in human patients, transfusion reactions may occur and your dog will have to be closely monitored during this transfusion. In dogs, transfusion reactions are rare after the first transfusion. However, if your dog has already received a blood transfusion, the risk for adverse reactions increases markedly. It is important to mention previous transfusions to your own veterinarian.
The spleen is the principal site of destruction of platelets during ITP. A surgery to remove the spleen has been advocated in severe cases of ITP which failed to respond to medical treatment. We rarely recommend this surgery in our hospital but this must be discussed with your own veterinarian.
If ITP is severe enough, hospitalisation in a referral hospital may be needed. In a referral hospital access to unusual medications, including human medication may be facilitated (e.g. intravenous human immunoglobulin, vincristine, mycophenolate mofetil).

Risks
ITP is considered to be idiopathic or primary when no underlying cause is found. Secondary ITP occurs when an underlying cause is identified which may include:

" Rickettsial infections e.g. Ehrlichia canis, Anaplasma phagocytophilum
" Drugs e.g. trimethoprim/sulfadiazine, cephalosporin
" Cancers

Any breed, sex or age of dog can be affected by ITP. It seems to be more common in middle aged, female dogs, particularly Cocker Spaniels, Old English Sheepdogs, Miniature and Toy Poodles.
People often worry that the ITP has been triggered by recent vaccination, as this link has been established in humans (although is exceedingly rare). In dogs it has not been proven that any vaccination causes ITP, and if it does occur it is also likely to be a rare event. It is very important to remember that many of the diseases your dog is vaccinated against are far more dangerous and common than the rare side effects associated with vaccination. If you are concerned about side effects of vaccination in dogs please discuss this with your veterinarian.

Prevalence
In a study of dogs in the USA, 5.2% of dogs admitted to a specialist veterinary hospital were found to have reduced numbers of platelets. Of these dogs 5% were diagnosed with ITP meaning it was the cause of 0.26% of hospital admissions.

This suggests that it is still a fairly uncommon disease, however it was the most likely cause of developing a very low platelet count (< 36,000,000 platelets/ml).

Outlook
The majority (>70%) of dogs with IMT (Immune-Mediated Thrombocytopenia) will show significant improvement with prednisolone alone or in combination with other immunosuppressive drugs in less than a week. After stabilisation with treatment, the doses are usually slowly tapered down while monitoring closely the platelet value.

During this progressive reduction in dose, there is a risk of recurrence of the clinical signs which may be observed in around 25% of the patients. Following recurrence, treatment should be reinstituted at a higher dosage and your veterinarian will discuss further treatment options.

Unfortunately, despite appropriate treatment around 10 to 15% of dogs with ITP can die or are euthanised at the beginning of the disease or after recurrence of their signs. This is mainly observed with severe disease associated with complications like coagulation disorders or severe gastro-intestinal bleeding. Rapid institution of the treatment and close monitoring during hospitalisation have been associated with reduced risk in dogs with ITP.


If you are owned by a dog or other pet with ITP and wish to use the services of the ITP Support Association, do feel free to join our Association or make a donation to help us with our work. There is no state funding for ITP research, and this charity cannot fund ITP research without help from those who have an interest in finding a cure, whether it be patient, family member, friend or pet owner.

Association's Veterinary Advisor
Andrew Kent BVSc DipECVIM-CA MRCVS

European Veterinary Specialist in Small Animal Internal Medicine
Willows Referral Service
Highlands Road
Shirley
Solihull
West Midlands B90 4NH
United Kingdom

www.willows.uk.net/specialist-services

References:

  • Botsch V., Hüchenhoff H., Hartman K. and Hirschberger J., "Retrospective study of 871 dogs with thrombocytopenia." Veterinary Record. 2009; 164, May, 23, 647-651.
  • Grindem C.B., Breitschwerdt E.B., Corbett W.T., Jans H.E., "Epidemiologic survey of thrombocytopaenia in dogs: A report on 987 cases." Veterinary Clinical Pathology 1991; 20: 38-43.
  • Huang A.A., Moore G.E., and Scott-Moncrieff J.C., "Idiopathic Immune-Mediated Thrombocytopenia and Recent Vaccination in Dogs," Journal of Veterinary Internal Medicine 26, No. 1, 142-148.
  • Laurel J. and Gershwin D.V.M., "Autoimmune Diseases in Small Animals," Veterinary Clinics of NA: Small Animal Practice 40, No. 3: 439-457.
  • O'Marra S.K., Delaforcade A.M., and Shaw S.P., "Treatment and Predictors of Outcome in Dogs with Immune-Mediated Thrombocytopenia." Journal of the American Veterinary Medical Association 238, No. 3: 346-352.
  • Putsche J.C., Kohn B., "Primary immune-mediated thrombocytopenia in 30 dogs (1997-2003)." Journal of the American Animal Hospital Association, 2008, 44, 250-257.

Teenage ITP

With thanks to Dr John Grainger and Chloe Goodall for this information.

Introduction
This page explains about immune thrombocytopenia (ITP), which is a blood problem affecting the platelets. It also explains what to expect when you are diagnosed with the condition.

What are platelets?
Platelets are one of the three types of blood cell, along with red and white blood cells. Platelets are small and sticky and their job is to prevent bruising and stop bleeding after an injury.

Platelets, like red and white blood cells, are formed in bone marrow which is at the centre of big bones, such as the femur and hip. A rough idea of how many platelets are present in the blood (platelet count) can be made using a sample of blood. The normal platelet count is between is 150 to 400 (UK measurement). In most cases of ITP the platelet count is less than 20. A low platelet count is called ‘thrombocytopenia’.

What is immune thrombocytopenia?
Immune thrombocytopenia is a medical term for a condition in which there is bruising (purpura) because there are fewer platelets in the blood than usual (thrombocytopenia) and is usually caused by something going wrong with the body’s defence against infection (immune system) or an allergic reaction of some kind.

How common is ITP and who does it affect?
About four in every 100,000 children develop ITP each year. In teenagers ITP is more common in girls than boys.

Chronic ITP is the term for ITP that has not gone away on its own after 12 months. Only 1 in 5 teenagers and adolescents with ITP will develop chronic ITP with teenage girls at highest risk. The majority of teenagers and adolescents with ITP will still have an improvement of the platelet count even if the ITP persists and the majority of teenagers and adolescents will still completely recover after a few years even if the ITP is still present at 12 months.

What are the symptoms of ITP?
Most teenagers and adolescents with a platelet count of under 20 will have pinprick blood spots under the skin (petechiae) and bruising. Bruising most commonly follows minor knocks ("easy bruising") but may also occur spontaneously without trauma. Apart from the bruising/ bleeding most adolescents are otherwise well. Common sites of spontaneous bleeding are the gums and nose. Girls may be troubled with heavy periods.

Tiredness and depression or other mood changes are commonly reported by people with ITP. This may be due to a change in chemicals which are carried by platelets.
Less common but potentially serious are spontaneous bleeds occurring from the gut or brain. Data from worldwide studies suggests that the risk of serious bleeds is about 3 in 100 and the risk of brain bleeds is about 1 in 300. The risk of serious bleeding is much lower when the platelet count recovers to over 20 x 109/Litre.

What causes ITP?
ITP commonly results from the immune system mistaking platelets as being foreign and attacking them. In many cases this may follow a viral infection or vaccination during which time the immune system attacks the virus but the immune system then goes on to think that the platelets are part of the virus and starts to attack the platelets.

How is ITP diagnosed?
ITP is usually diagnosed using a blood test called a ‘full blood count’. When a sample of your blood is looked at under a microscope, a blood doctor can examine each blood cell type closely. This is to rule out other conditions that may cause similar symptoms to ITP. If the platelets, red blood cells and white blood cells all look normal, this rules out blood cancer (leukaemia). If the low platelet count improves quickly and no treatment is needed, you will not need any further tests.

If the platelet count is not showing signs of recovery by 3 to 6 months then a small sample of bone marrow will need to be taken and looked at under the microscope. Additional blood tests may be taken at this time to rule out rare problems with making blood clots and rare problems of the immune system that can look like ITP. If the bone marrow looks normal, with the usual or higher number of cells that make platelets (megakaryocytes), and other blood tests are normal, then the doctor will diagnose persistent ITP.

How is ITP treated?

Most teenagers and adolescents do not need any treatment unless they have severe bleeding, and most teenagers and adolescents improve whether or not treatment is given. The type of treatment recommended depends on your symptoms rather than your platelet count. Most treatments aim to temporarily improve the platelet count and do not cure the condition itself. When treatments are considered, you will have the chance to discuss the risks and benefits of these, as opposed to no treatment, with the doctor. The options for treating ITP include:

1) No treatment
The majority of teenagers and adolescents with ITP have a low platelet count but do not have dangerous bleeding. Without treatment most teenagers and adolescents will have a platelet count over 20 within 5 days and a normal platelet count by six months.

2) Tranexamic acid
Tranexamic acid does not increase the platelet count but does help the blood to produce clots. It is particularly useful for gum bleeds, nose bleeds or heavy periods and helps the blood to form clots without altering the platelet count. It is best taken as a liquid ("swish and swallow") three times per day. It must not be used if there is any blood in the urine.

3) Hormonal treatment
Norethisterone is a drug used to stop girls' periods. This is done if their periods are extremely heavy.

Oral contraceptive pill – teenage girls with ITP can be put on the oral contraceptive pill to try and reduce heavy periods.

4) Steroid treatment
Steroids are sometimes given to teenagers and adolescents with ITP on a short-term basis in an attempt to increase their platelet count. However, when the steroid dose is reduced, the platelet count will drop again after a few days. Steroids should only be given for a short period of between 4 to 7 days.

Side effects such as weight gain and mood changes are common. Some teenagers and adolescents become very worried about their mood changes when they’re on steroids, so it is important to know that this is a perfectly normal side effect of the drug, as is increased appetite and disturbed sleep patterns.
Steroids can also affect your skin; you may notice that you get more spots while you are on the tablets.
Longer courses of steroids are not recommended as this may dampen the immune system, weaken bones, cause diabetes or obesity and stunt growth.

5) Intravenous immunoglobulin
Immunoglobulins are antibodies which can reduce platelet destruction. They are a blood product produced from many donors and have a theoretical but very low risk of transmitting blood-borne infections. One course of treatment with immunoglobulin takes a full day as an in-patient in the hospital and the benefit will usually last about a month. Side effects such as fever and headaches are common.

6) ‘Curative’ treatments

Splenectomy
In ITP the majority of platelets are destroyed in the spleen. Removing the spleen (splenectomy) is often effective in preventing early destruction of the platelets and allows the count to rise. In teenagers and adolescents however this is rarely necessary unless the ITP persists and the child has recurrent severe bleeds. It is successful in about 3-4 out of 5 people. Splenectomy is a major surgical procedure and carries a long term risk of severe infection and blood clots. It is rarely performed as the risks of splenectomy usually outweigh the potential benefits. Alternative treatments such as rituximab or the newer TPO-mimetics are usually tried prior to considering splenectomy.

Rituximab
Rituximab kills the immune cells that clear the platelets out of the blood. By removing the cells that get rid of the platelets, the platelet count will increase. It is successful initially in about 2 in 3 people and can be curative in about one third. Side effects are common.

Eltrombopag and Nplate
These TPO-mimetic newer drugs increase the number of platelets that are made in the bone marrow without suppressing the immune system. They are currently not widely available for children or teenagers.

What about school, sport and holidays?
Most severe bleeds tend to occur in the first week it develops and in teenagers and adolescents with a platelet count under 20. In those teenagers and adolescents with a count over 20 they can return to school/college/university immediately after the head teacher/tutor has been informed about the ITP. In teenagers and adolescents with a lower platelet count school can resume after the first week and when the school has been informed. The ITP Support Association produces a leaflet for schools/colleges/universities and clubs (available free of charge to members).

If you are on steroids and haven’t had chicken pox then school will need to inform you if anyone in your class goes down with chicken pox.
As a general rule contact sports where there is a risk of head injury should only be undertaken with care with active ITP. When the platelet count is over 50 the only sports to avoid would be rugby, boxing and wrestling where serious injuries can occur. Below this level it is possible to undertake supervised training but taking precautions to wear the appropriate protective gear. These are only recommendations, and you should discuss with your doctor what you can and cannot do as everyone is different.
Common sense is important. You should take the proper precautions that each sport requires, for example you must wear a helmet if you go cycling and you should not run around the sides of a swimming pool, but everyone should be doing this anyway. Because you will bruise more easily than most people, it is a good idea if you wear knee and elbow pads during certain sports.
At school, you need to make sure your teachers are aware of your condition, and it is best if your parents do this with you.

It is best not to take any holidays abroad in the first three months of ITP as it may be difficult to get insurance. After this time most cases of ITP will have resolved. If the ITP does persist you will need to discuss further with your doctor and you may need specialist medical insurance. A list of recommended insurance companies is given in the ITP Support Association’s Holiday Guide (available free of charge to members)

What else can I do?
You should also avoid drugs like aspirin, ibuprofen or herbal medication which can increase the risk of bruising and bleeding. Finally, you should make sure that doctors and dentists and any other medical practitioner you see know that you have a low platelet count.

When to seek help?
When you’re sent home you will be given a clinic appointment for review at the hospital and an emergency number (usually the phone number to the hospital ward). You should tell your mum, dad or guardian if the following ever happen so they can contact the hospital:

  • A nosebleed which will not stop after 30 minutes despite pinching the nose
  • Prolonged gum bleeding
  • Blood in the poo or urine
  • Following a heavy blow to the head, particularly if you are stunned or sickly
  • Persistent or severe headache
  • Vomiting or drowsiness
  • If you haven’t had chicken pox and someone you meet or at school has the virus

Is there a UK registry?
To maintain accurate numbers of cases of childhood ITP and investigate possible markers for risk of severe bleeding a UK registry has been established (www.uk-itp.org) Families may be routinely asked to consent for anonymous data to be stored on the registry.

Further reading
The ITP Association has a booklet ITP ‘n’ Stuff specifically written for teenagers at school with ITP, available free of charge to members.

Adult ITP

What is ITP
Immune thrombocytopenia (formerly known as idiopathic thrombocytopenic purpura) is a medical term for an autoimmune disorder (immune) causing a shortage of platelets (thrombocytopenia) and bruising (purpura).

What is the cause of ITP
ITP is an autoimmune disease in which the immune system mistakes the platelets as being foreign and destroys them. It can follow a virus, vaccination or certain medications, but for most people the cause is unknown.

ITP that arises suddenly is known as acute ITP, if the platelet count remains low after 3 months it will be called persistent ITP, and if the platelet count has not returned to normal after 12 months it will be called chronic ITP. The severity of the condition is determined by adding the names severe or mild. Thus, for example, someone with chronic severe ITP would have had a troublesome condition with a very low platelet count for over a year.

How is ITP diagnosed?
ITP is usually diagnosed by a blood test showing that only the platelet count is low, and the platelets, red blood cells and white blood cells all look normal. A bone marrow biopsy may be taken at a later stage if the ITP continues, in which a small sample of bone marrow will be taken under local anaesthetic and examined under the microscope. Additional blood tests may be taken at this time to exclude rare clotting or immune diseases that can mimic ITP. If the bone marrow looks normal, with the usual or higher number of platelet parent cells (megakaryocytes) and other blood tests are normal then the doctor will diagnose chronic ITP.

What are platelets?
There are three types of blood cell which are all formed in the bone marrow; red cells, white cells and platelets. Platelets, which are small and sticky and circulate in the bloodstream provide the inital plug to stop bruising and bleeding after an injury, and stop blood leaking from capilleries. A blood sample is taken to measure the circulating platelets, and in most people there are between 150,000 and 400,000 platelets in every cubic millimetre of blood. However in the UK we simplify this by describing a platelet count of, say, 150 rather than 150,000. Anyone with a count less than 100 would be considered thrombocytopenic (ie. short of platelets). Many people with ITP have a platelet count in single figures, and on rare occasions there are not enough circulating platelets to be counted, thus the count is given as 0. The number of platelets circulating in our bodies fluctuates all the time, and thus no two consecutive platelet counts are likely to be exactly the same either in a healthy person or in an ITP sufferer.

What is the difference between ITP and hæmophilia?
Hæmophilia is inherited and permanent, ITP is not inherited, and can go into remission. Hæmophilia patients are deficient in one of the 12 factors which act together to form a blood clot. ITP patients are short of platelets which work independently as the initial plug to stop blood leakage, but the rest of the clotting mechanism works normally. Platelet infusions are only used in emergencies as transfused platelets, like the patient’s own platelets, are destroyed by their immune system in a matter of hours.

What is the incidence of ITP?
In the UK about 3,000 to 4,000 of the population have ITP at any one time, and it is not more prevalent in any particular racial or ethnic group.

What are the symptoms of ITP?
Some people with ITP, especially those with a count over 50, may have no symptoms at all, and their ITP only noticed during a routine blood test. Even people with very low counts, can sometimes have few symptoms.

Common symptoms are:
petechiae (pinprick rash of blood spots)
bruising
nosebleeds
gum bleeds
black mouth blisters
fatigue
heavy periods

Rare symptoms are:
blood in the eyes

bleeding from the ears
blood in the urine
bleeding from the gut
bleed into the brain

How is ITP treated?
Some adults with mild ITP may not need any treatment, but will be monitored with occasional blood tests. There is no cure for ITP and treatment is used to raise the platelet count to counteract symptoms.

First line treatments include prednisolone and intravenous immunoglobulin (under various brand names).

Second line treatments include splenectomy, azathioprine, cyclosporin, cyclophosphamide, vinca alkaloids, danazol, dapsone, rituximab, eltrombopag, romiplostim and mycophenlate mofetil.

Tranexamic acid may be used for dental extractions. Hormone preparations and/or tranexamic acid may be prescribed to women having heavy periods.

Platelet transfusions may be used to stem active bleeding or during surgery, but they are ineffective as a treatment for ITP as the immune system destroys transfused platelets as quickly as the body’s own platelets.

When to seek help?
You should contact the hospital in the following circumstances:

A prolonged (over 30 minutes) nosebleed which will not stop despite pinching the nose
Prolonged gum bleeding
Blood in the faeces or urine
A heavy blow to the head
Persistent or severe headache with loss of vision, vomiting or drowsiness
Very heavy periods (eg. lasting 8 -10 days, changing more than 9 tampons/pads per day, changing protection during the night, passing clots on 2 consecutive days)


The ITP Support Association is grateful to Professor Adrian Newland and Dr John Grainger for their assistance in the preparation of this page.

 

Further reading: The ITP Support Association's core booklet Know About ITP (free to members and sent out with the initial information pack) explains about ITP, its management, treatment options, general outlook, ITP in pregnancy, and referral and second opinion on the NHS.

News and Events

The 2016 ITP Patient Convention was held on Saturday 17th September at Cumberwell Park Golf Club and was a great success, enjoyed by everyone who attended. We are now in the process of planning for the 2017 Patient Convention which will be held at a venue in Central London, sometime in May 2017.

Read more ...