By James Warland, Andrew Kent, Julien Bazelle, and Professor Michael Herrtage Cambridge University’s Queen’s Veterinary School Hospital
The body’s first line of defence against bleeding is composed of thrombocytes, or platelets. They are minute pieces of blood-borne cells that are created in the bone marrow. All of the body’s vessels are continually being patrolled by these pieces, which will form a clot if the vessel wall is harmed in any way. In order for your dog’s blood to operate normally, there should be over 175,000,000 platelets per millilitre (up to 500,000,000/ml). The platelets are the first component of clot formation, but if the blood vessel is damaged in any way, more components are needed for a strong clot to develop. The blood is unable to fast clot normally if there are not enough platelets present. The dog’s own immune system assaults and eliminates these platelets in a disease known as immune mediated thrombocytopenia. Although thrombocytopenia is the sole issue in the majority of instances, ITP can occasionally be a symptom of a more serious autoimmune disorder that affects other organs. Examples of this include Systemic Lupus Erythematosus (SLE), in which the body attacks numerous tissues, and Evan’s Syndrome, in which the body attacks both the platelets and red blood cells (resulting in anaemia).
causes and screening procedures In most cases, the initial aetiology of ITP is unknown. ITP is brought on by an autoimmune reaction against the dog’s own platelets. It could be a core issue or a secondary one brought on by other illnesses. Your veterinarian will need to do certain tests on a dog with irregular bleeding to determine the cause. Blood tests will reveal thrombocytopenia, or reduced platelet counts, however it is important to understand that ITP is not the only cause of thrombocytopenia. Your dog’s veterinarian may decide to perform additional tests to search for an underlying cause of the thrombocytopenia based on their findings and the previous medical history of your dog. ITP may result from a number of infections, including bacterial and viral infections. Ehrlichia, which is spread by ticks and is the most significant type of infection to cause thrombocytopenia in the UK, can be tested for by your veterinarian if an infection is suspected. To rule out other thrombocytopenic reasons, your veterinarian may also run other examinations on your dog, such as X-rays and ultrasounds. Antibiotics and anti-inflammatory medications in particular might result in thrombocytopenia. Unfortunately, ITP is only identified after other probable reasons of low platelet counts have been ruled out. If your dog has visited a country outside the UK, it is crucial to let your veterinarian know because there are a number of non-UK illnesses that can cause thrombocytopenia and it may be necessary to test for them as well.
Clinical Symptoms The most prevalent clinical symptoms in dogs with ITP are those related to bleeding. Dogs typically exhibit bleeding symptoms even when there has been no apparent trauma because clots are constantly being created to stop bleeding. ITP frequently manifests as nosebleeds, bruising of the skin or gums, or petechiae (a tiny, red spotted rash brought on by bleeding capillaries). Some dogs experience internal bleeding that is not immediately visible but results in faeces that are dark and tar-like (melaena). Some canines can experience more unusual bleeding, such as bleeding in the brain or the eye, which might cause additional issues.
Treatment The initial goal of treatment for ITP is to lessen the hyperactive immune system that is responsible for this platelet decrease. Immunosuppressive medicines are those that are used to reduce immune system hyperactivity. Prednisolone continues to be the most often administered corticosteroid, which is the principal class of immunosuppressive medications. Prednisolone dosages differ significantly amongst patients, however high doses are frequently utilised at the start of the course of treatment. Prednisolone may cause negative effects, just like any medicine (e.g. increased drinking and urination, increased appetite, weakness, or rarely vomiting or diarrhoea). Some canine patients can be treated for an extended period of time with simply prednisolone because these adverse effects are significantly less common than in human patients. Your own veterinarian may also prescribe alternative immunosuppressive medications if prednisolone alone is unable to treat the clinical signs or if side effects are noted (e.g. azathioprine, cyclosporine). Your veterinarian might advise transfusion of new canine blood or other blood components if the platelets level is critically low and bleeding has taken place. Similar to human patients, your dog will need to be constantly watched during this transfusion because transfusion reactions are possible. After the initial transfusion, transfusion reactions in dogs are uncommon. The risk for unpleasant reactions sharply rises if your dog has already had a blood transfusion. It is crucial to let your personal veterinarian know about prior transfusions. The main location where platelets are destroyed with ITP is the spleen. In extreme cases of ITP that did not respond to medical treatment, spleen removal surgery has been recommended. In our hospital, we don’t often advise this surgery, but you should talk to your personal veterinarian about it. ITP may require hospitalisation at a referral hospital if it is severe enough. Access to odd pharmaceuticals, especially human medication, may be made easier in a referral hospital (e.g. intravenous human immunoglobulin, vincristine, mycophenolate mofetil).
Risks If there is no identified underlying aetiology for ITP, it is referred to as idiopathic or primary. When an underlying cause of secondary ITP is discovered, it may include: “Drugs such as trimethoprim/sulfadiazine, cephalosporin,” “Rickettsial infections such as Ehrlichia canis, Anaplasma phagocytophilum,” and “Cancers.”
ITP can have an impact on dogs of any breed, gender, or age. In middle-aged, female dogs, especially Cocker Spaniels, Old English Sheepdogs, Miniature and Toy Poodles, it appears to be more prevalent. Given that this connection has been demonstrated in humans, people frequently worry that a recent vaccine has caused them to develop ITP (although is exceedingly rare). It has not been established that any immunisation in dogs causes ITP, and even if it did, it is most likely an uncommon occurrence. It is crucial to keep in mind that compared to the uncommon adverse effects of vaccination, many of the diseases your dog is protected against are much more deadly and prevalent. Please talk to your veterinarian if you have any concerns regarding the adverse reactions that dogs may experience from vaccinations.
Prevalence 5.2% of dogs hospitalised to a specialised veterinary facility in the USA were found to have lower than normal levels of platelets, according to a research on canines there. ITP was the reason of 0.26% of these dogs’ hospital stays because 5% of them had the diagnosis.
The fact that it was the most likely reason for the development of a very low platelet count ( 36,000,000 platelets/ml) implies that the condition is still quite uncommon.
Outlook Prednisolone alone or in combination with other immunosuppressive medications will significantly treat the majority (>70%) of dogs with immune-mediated thrombocytopenia (IMT) in less than a week. Following therapy stabilisation, the doses are often gradually reduced while the platelet value is constantly monitored.
There is a chance that the clinical indicators will come back during this gradual dose reduction, which may be seen in about 25% of the patients. The treatment should be restarted after a recurrence at a larger dosage, and your veterinarian will go through additional treatment alternatives.
Unfortunately, despite receiving the right care, between 10 and 15 percent of dogs with ITP die or are put to sleep at the outset of the illness or following a recurrence of their symptoms. The majority of the time, this is seen in serious diseases that have complications like coagulation issues or significant gastrointestinal bleeding. In dogs with ITP, a reduced risk has been linked to early treatment initiation and close monitoring while in the hospital.
European Veterinary Specialist in Small Animal Internal Medicine Willows Referral Service Andrew Kent, BVSc, DipECVIM-CA, MRCVS Highlands Avenue United Kingdom Shirley Solihull West Midlands B90 4NH
Canines who have ITP recover?
A detailed history and physical examination are the first steps in determining whether an animal has platelet disease.
A blood sample will be taken so a platelet count can be done. A machine-generated count is insufficient to validate a low count because platelets might clump together in a blood sample, making it appear low. A qualified professional should thus make a blood smear and analyse it under a microscope. Several properties of the platelets can be seen by microscopic examination of a blood sample:
- Platelet fragments are a sign that the immune system is targeting the platelets.
- On a blood smear, several heritable breed-specific disorders that result in low platelet counts can be identified.
- On a blood smear, several infectious reasons of a low platelet count can be seen.
Additional diagnostic procedures can be used to confirm or exclude some platelet-related disorders. Since the bone marrow is where platelets are produced, a sample of the bone marrow can be examined under a microscope to ascertain whether the cause of thrombocytopenia is related to a problem with platelet formation. Additionally, a number of disorders acquired through ticks can result in thrombocytopenia, therefore it’s crucial to run testing to rule out tick-borne illnesses. Last but not least, factors other than platelets may cause other coagulation components to malfunction. The condition of these coagulation components can be checked using particular assays. Typically, ITP is diagnosed only after all other potential causes of low platelet counts have been ruled out.
- Immunosuppressive medications: Steroids like prednisone can prevent platelets from being destroyed by cells. Additional immunosuppressive medications are available if prednisone fails to function or if the side effects are intolerable (eg. azathioprine, cyclosporine).
- Vincristine is a chemotherapeutic drug that has the potential to temporarily enhance platelet counts.
- Intravenous immunoglobulin: In some animals, this blood product with antibodies can temporarily stop the rapid loss of platelets.
- Supportive care entails avoiding any actions that could result in bleeding, limiting exercise, and cage rest. Patients should be constantly watched for any signs of uncontrollable bleeding. To replace missing red blood cells, a blood transfusion may frequently be necessary. Rarely is a specific platelet transfusion also required.
ITP has a mixed prognosis, ranging from favourable to cautious. Although roughly 80% of dogs with this sickness will recover, the remaining 20% will either be put down or pass away as a result of the illness. Prognosis has been demonstrated to depend on a number of variables. Patients who experience melena (blood in the stool), have elevated kidney values on blood tests, or need blood transfusions may struggle to recover from the illness.
Even in cases where a dog responds well, recurrence could happen later. According to research studies, relapse rates might range from 9 to 31%. Unfortunately, there is a 50% risk that a dog will relapse after experiencing one. Usually, the first recurrence happens a year or less after the first diagnosis.
The core of ITP management is steroids, although these medications have a number of adverse effects. Similar to humans, animals getting steroid therapy will experience an increase in hunger that could result in weight gain. They frequently show increased urination and thirst. Inappropriate steroid administration might also result in other problems, necessitating close observation. In addition, while immune system suppression will aid in the management of ITP, it will also increase the animal’s susceptibility to infections.
Fortunately, most people do not need to take immunosuppressive drugs forever. Steroids are frequently provided in a “tapering dose,” which means that their dosage is gradually reduced over a period of months. Every time the dosage of immunosuppressive medicines is changed, further platelet counts should be done. Owners of pets should be aware of the clinical symptoms of thrombocytopenia and the need of continuing to watch for these symptoms.
How is ITP in dogs managed?
*NOTE: Idiopathic thrombocytopenic purpura, the term of the comparable human disorder, is where the acronym ITP comes from. This article will refer to the canine type of immune-mediated thrombocytopenia by the abbreviation that is most frequently used.
A significant contributor to severe canine thrombocytopenia is immune-mediated thrombocytopenia (ITP). Platelet autoantibodies are produced in ITP patients and bind to their surface, making them a target for macrophage eradication. As a result, there is severe thrombocytopenia, with platelet counts frequently falling below the 30,000–50,000 platelets/uL level that is thought to indicate a significant risk of spontaneous bleeding. Any patient presenting with unexplained bleeding, bruises, or petechiae should have ITP as a top contender in the differential diagnosis.
ITP can be primary, in which case the cause of the immune reaction against the platelets has not been identified, or secondary to the occurrence of another disease process or drug administration. Secondary ITP should be considered in any patient using a sulfa medicine for more than five to seven days who experiences unexplained thrombocytopenia, bleeding, or bruising. Sulfa-based therapies are often reported ITP triggers. Penicillins and cephalosporins are two other antibiotics that have been linked to ITP cases. There is no proven connection between canine ITP and vaccination, despite the fact that temporary thrombocytopenia has been linked to immunisation. 1 Secondary ITP is frequently brought on by infectious disorders, especially those spread by ticks. In dogs with thrombocytopenia who also tested positive for Babesia, Ehrlichia, anaplasma, leishmania, leptospirosis, heartworm, and Rocky Mountain spotted fever, platelet autoantibodies were discovered, providing evidence of immune-mediated platelet destruction. 2, 3 ITP can also be accompanied by neoplasia, with lymphoma being the most typical cause. Always treat the underlying illness process or stop the triggering medication as part of secondary ITP treatment.
Despite the fact that ITP can affect dogs of any age or breed, middle-aged female dogs tend to be particularly susceptible, and cocker spaniels are the breed most frequently associated with the condition.
4 ITP patients may exhibit bruises, petechiae (capillary haemorrhages), bleeding, or less specific symptoms including lethargy and decreased appetite. In one study, petechiae or ecchymoses—present in 66% of all ITP patients at presentation—were the most prevalent indications of bleeding in the 81% of dogs who showed up with them. 20% of cases were found to have hematemesis, melena, or gingival bleeding; other less frequent bleeding symptoms included hyphema, hematuria, and epistaxis. 4 Individuals with ITP rarely experience cavitary bleeding (such as hemoabdomen or hemothorax), but patients with coagulopathy more frequently do. According to one study, a third of patients had a fever. 4
Due to their extremely low platelet counts (50,000 platelets/uL), dogs with ITP are more susceptible to spontaneous bleeding. One study indicated that dogs with ITP had lower platelet counts and a higher incidence of anaemia than dogs with thrombocytopenia from any other cause. The majority of publications on ITP in dogs report median platelet counts on presentation in the range of 1000–5000 platelets/uL,1, 4, 5. 6 ITP dogs frequently have anaemia when they first come, and a total blood count may reveal further abnormalities that point to an inflammatory response, such as leukocytosis, an increase in band neutrophils, and toxic change. It’s important to remember that the presence of these changes does not necessarily signify infection; rather, they can be noticed as a result of the ITP’s prominent systemic inflammation.
The diagnosis of ITP is often presumptive based on the presence of severe thrombocytopenia in the absence of any other cause, even if platelet-bound antibodies can be detected using flow cytometry. Testing for infections spread by ticks, chest x-rays, and abdomen ultrasounds to check for neoplasia are all recommended as part of the diagnostic workup for secondary ITP. A broader tick screening can be helpful to look for other diseases including Rocky Mountain spotted fever and Babesiosis whereas point-of-care testing, such as 4dx, is a beneficial initial step in evaluation for tickborne diseases. Babesia infection screening should be taken into consideration, especially in overrepresented breeds like pit bull terriers and greyhounds. Doxycycline is frequently used as part of first therapy for ITP to treat the majority of tickborne infections due to the high prevalence of tickborne illness in New England.
Figure 1 shows a patient’s shaved ventral abdomen, which shows petechiae and ecchymoses. The patient has ITP as a result of taking trimethoprim-sulfamethoxazole.
Immunosuppressive corticosteroid medication, often administered as prednisone starting at 2 mg/kg/day (or 30 mg/m2 for larger-breed dogs), is the basis of treatment for ITP. Once the platelet count has stabilised, this dose is gradually decreased, typically by 25% every two to four weeks. Following each dose reduction, the platelet count needs to be checked to make sure there hasn’t been a recurrence. Additional immunosuppressive drugs, such as cyclosporine, mycophenolate, and azathioprine, are routinely administered in an effort to improve disease control or lessen the need for corticosteroids. There isn’t any proof, though, that using these drugs in addition to steroids increases the likelihood of survival as compared to using steroids alone. 7 There is also disagreement on the appropriate secondary immunosuppressive medication; in one trial, the use of mycophenolate in combination with steroids had no different results from the use of cyclosporine. 8
There are numerous additional complementary treatments that aid ITP patients more directly. It has been demonstrated that giving ITP patients a single dose of human intravenous immunoglobulin (hIVIG) can shorten their stay in the hospital and speed up platelet recovery above 40,000 platelets/uL. The positive effects of hIVIG are assumed to result from its capacity to inhibit Fc receptors on phagocytic cells, hence lowering the capacity of these cells to lyse platelets that have been autoantibody-tagged. 5 One study indicated that vincristine is equal to hIVIG in its ability to shorten hospital stays and platelet recovery times after a single dosage administration, which has been shown to speed up this process. 9 Vincristine is frequently the first option for supplementary therapy in ITP cases because it is less expensive and simpler to administer than hIVIG. Romiplostim, a thrombopoietin-receptor agonist used to promote platelet formation in human patients with ITP, is a fairly novel yet promising approach in the treatment of ITP. Four of the five dogs with ITP in a tiny pilot study experienced a rise in platelet count after receiving a single dosage of Romiplostim, and the fifth dog eventually had an increase after receiving repeated and higher doses. 10 Although the price of this medication currently prevents canine patients from using it, it might be used more frequently in the future.
ITP is a dangerous condition that occasionally results in fatal haemorrhage, although the prognosis is generally good, with about 75-90 percent of patients making it to hospital discharge and 63-80 percent surviving.
4, 11 Melena and a high BUN level have both been identified as poor prognostic factors. In one study, compared to 85–90% of canines without these alterations, only about 60% of patients with melena or increased BUN made it to discharge. 4 Melena and an increased BUN level could both be signs of more serious gastrointestinal bleeding, which would necessitate additional transfusions and have a poorer outcome. Recent investigations have found reported rates of ITP relapse ranging from 9 to 39%. 4, 7, 11 ITP relapses can happen years after initial diagnosis and occur at varying times for different people. Therefore, even after years of immunosuppressive therapy-free remission, dogs with a history of ITP should continue to have routine complete blood counts checked.
Even while ITP patients frequently need close observation and extensive care at the time of diagnosis, they can thrive when receiving the right immunosuppressive medicine. The majority of patients will endure long enough to be released from the hospital.