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IMMUNE-MEDIATED THROMBOCYTOPENIA (ITP) IN DOGS
By Lisa Gorman, DVM, DACVIM
angell.org/internalmedicine
MSPCA-Angell West
781-902-8400
*NOTE: The abbreviation ITP is from the name for the analogous human condition,
idiopathic thrombocytopenic purpura. This is the abbreviation that is used most
commonly for the canine form of immune-mediated thrombocytopenia and will be
used throughout this article.
Immune-mediated thrombocytopenia (ITP) is an important cause of severe
thrombocytopenia in dogs. In patients with ITP, platelet autoantibodies are made
and attach to the surface of platelets, targeting them for destruction by
macrophages. This results in profound thrombocytopenia, with platelet counts
commonly below the threshold of 30,000-50,000 platelets/uL that is considered
high risk for spontaneous bleeding. ITP is a major differential to consider in
any patient presenting with unexplained hemorrhage, bruising, or petechiae.
ITP can be primary, in which no underlying trigger for the immune response
against platelets is discovered, or it can be secondary to another disease
process or medication administration. Sulfa-based medications are commonly
reported triggers for ITP, and secondary ITP should be suspected in any patient
using a sulfa drug for longer than five to seven days who has unexplained
thrombocytopenia, bleeding, or bruising. Other antibiotics such as penicillins
and cephalosporins have also been implicated in ITP cases. Although vaccination
has been associated with transient thrombocytopenia, there has been no
established link between ITP and vaccination in dogs.1 Infectious diseases,
particularly tickborne infections, are frequent causes of secondary ITP.
Platelet autoantibodies have been found in thrombocytopenic dogs positive for
Babesia, Ehrlichia, anaplasma, leishmania, leptospirosis, heartworm, and Rocky
Mountain spotted fever, indicating that immune-mediated platelet destruction is
present.2, 3 Neoplasia can also be associated with ITP, with lymphoma implicated
most commonly. Treatment of secondary ITP should always include treatment of the
underlying disease process or discontinuation of the triggering medication.
Although ITP can occur in any age or breed of dog, middle-aged female dogs
appear to be at greatest risk, and cocker spaniels are the most commonly cited
breed predisposition.4 Patients with ITP may present with unexplained bruising,
petechiae (capillary hemorrhages), bleeding, or more vague signs such as
lethargy and decreased appetite. In one study, 81% of dogs presented with signs
of bleeding, the most common of which was petechiae or ecchymoses (present in
66% of total ITP cases on presentation). Hematemesis, melena, and gingival
bleeding were each reported in approximately 20% of cases, while less common
signs of bleeding included epistaxis, hematuria, and hyphema.4 Cavitary bleeding
(such as hemoabdomen or hemothorax) is rare in patients with ITP and is more
commonly noted in patients with coagulopathy. Fever is common, noted in about
one third of patients in one study.4
Dogs with ITP typically have very low platelet counts (<50,000 platelets/uL),
which puts them at risk of spontaneous bleeding. Most studies of ITP in dogs
report median platelet counts on presentation in the range of 1000-5000
platelets/uL,1, 4, 5 and another study found that dogs with ITP had lower
platelet counts and a higher incidence of anemia than dogs with thrombocytopenia
from any other cause.6 ITP dogs are commonly anemic on presentation and may have
other changes on a complete blood count indicative of an inflammatory response,
including leukocytosis, increased numbers of band neutrophils, and toxic change.
It is important to note that the presence of these changes does not necessarily
indicate infection, but rather can be seen simply due to the marked systemic
inflammation that occurs with ITP.
Although platelet-bound antibodies can be detected using flow cytometry, this is
not commonly done, so diagnosis of ITP is typically presumptive based on the
presence of severe thrombocytopenia without another explanation. Recommended
diagnostic workup for possible causes of secondary ITP includes testing for
tickborne diseases, as well as chest x-rays and abdominal ultrasound to look for
evidence of neoplasia. While point-of-care testing such as 4dx is a useful first
step in evaluation for tickborne diseases, a broader tick screening can be
useful to look for other diseases such as Rocky Mountain spotted fever and
Babesiosis. Screening for Babesia infection should be considered particularly in
overrepresented breeds, such as greyhounds and pit bull terriers. Due to the
high prevalence of tickborne disease in New England, it is also common practice
to administer doxycycline as a part of initial therapy for ITP to cover for the
majority of tickborne diseases.
Figure 1: The shaved ventral abdomen of a patient with ITP secondary to
administration of trimethoprim-sulfamethoxazole, displaying petechiae and
ecchymoses.
The mainstay of treatment for ITP is immunosuppressive corticosteroid therapy,
usually given as prednisone starting at 2 mg/kg/day (or 30 mg/m2 for
larger-breed dogs). This dose is gradually reduced once the platelet count has
returned to normal, typically with dose reductions of 25% every two to four
weeks. Platelet count should be monitored after each dose reduction to make sure
there is no sign of relapse. Adjunctive immunosuppressive medications, including
cyclosporine, mycophenolate, and azathioprine, are also frequently used in an
attempt to better control the disease or reduce the corticosteroid requirement.
However, there is no concrete evidence that use of these medications in addition
to steroids provides a significant survival benefit when compared to steroids
alone.7 There is also no consensus on which secondary immunosuppressive drug is
best; in one study, there was no difference in outcome in dogs treated with
mycophenolate when compared to cyclosporine when each was used in combination
with steroids.8
There are several other adjunctive therapies that have more tangible benefits in
ITP patients. A single dose of human intravenous immunoglobulin (hIVIG) has been
shown to reduce the time to platelet recovery above 40,000 platelets/uL and to
reduce the required hospitalization time in ITP patients. hIVIG’s beneficial
effect is thought to be due to its ability to block Fc receptors on phagocytic
cells, thereby reducing their ability to destroy platelets that are tagged with
autoantibodies.5 Administration of a single dose of vincristine has also been
shown to speed platelet recovery, and in one study, it was found to be
equivalent to hIVIG in its effect on reducing platelet recovery time and
hospitalization time.9 Since vincristine is less expensive and easier to
administer than hIVIG, it is often the first choice for adjunctive therapy in
ITP cases. A more novel but promising option in the treatment of ITP is the use
of Romiplostim, a thrombopoietin-receptor agonist that is used to stimulate
platelet production in human patients with ITP. In a small pilot study of five
dogs with ITP, platelet count increased after a single dose of Romiplostim was
given in four of the dogs, and the fifth dog ultimately had an increase in
platelet count after repeated and increased dosing.10 While the cost of this
medication currently makes its use impractical for canine patients, it may
become more widely utilized in the future.
Although ITP is a serious disease that can result in fatal hemorrhage in some
cases, the prognosis is generally good, with approximately 75-90% of patients
surviving to discharge from the hospital and 63-80% surviving
long-term.4, 11 Melena and elevated BUN have both been found to be negative
prognostic indicators. In one study, only about 60% of patients with melena or
elevated BUN survived to discharge, versus 85-90% of dogs without these
changes.4 Both melena and elevated BUN may be indicators of more severe
gastrointestinal bleeding, leading to a greater transfusion requirement and
worse prognosis. Reported rates of ITP relapse vary widely in recent studies,
ranging from 9-39%.4, 7, 11 Time to relapse of ITP also varies greatly between
individuals and can occur years after initial diagnosis. Therefore, dogs with a
history of ITP should still have complete blood counts monitored routinely, even
when they have been in remission and off immunosuppressive medications for
years.
While ITP patients often require intensive care and monitoring at the time of
diagnosis, they can do very well with appropriate immunosuppressive therapy.
Most patients will survive to discharge from the hospital, and many attain
long-term survival.
References
1. Idiopathic immune-mediated thrombocytopenia and recent vaccination in dogs.
Huang, A.A. et al. J Vet Intern Med 2012; 26: 142-148.
2. Underlying diseases and clinicopathologic variables of thrombocytopenic
dogs with and without platelet-bound antibodies detected by use of a flow
cytometric assay: 83 cases (2004-2006). Dircks, Brigitte Hedwig et al. J Am
Vet Med Assoc 2009; 235: 960-966.
3. Secondary immune-mediated thrombocytopenia in dogs naturally infected by
Leishmania infantum. Cortese, L. et al. Veterinary Record 2009; 164:
778-782.
4. Treatment and predictors of outcome in dogs with immune-mediated
thrombocytopenia. O’Marra, Shana K. et al. J Am Vet Med Assoc 2011; 238:
346-352.
5. A prospective, randomized, double-blinded, placebo-controlled study of
human intravenous immunoglobulin for the acute management of presumptive
primary immune-mediated thrombocytopenia in dogs. Bianco, D. et al. J Vet
Intern Med 2009; 23: 1071-1078.
6. Retrospective study of 871 dogs with thrombocytopenia. Botsch, V. et al.
Veterinary Record 2009; 164: 647-651.
7. Outcome based on treatment protocol in patients with primary canine
immune-mediated thrombocytopenia: 46 cases (2000-2013). Scuderi, Margaret
Ann et al. Can Vet J 2016; 57: 514-518.
8. Treatment of presumptive primary immune-mediated thrombocytopenia with
mycophenolate mofetil versus cyclosporine in dogs. Cummings, F.O. et al.
Journal of Small Animal Practice 2017; 58: 96-102.
9. A prospective randomized clinical trial of vincristine versus human
intravenous immunoglobulin for acute adjunctive management of presumptive
primary immune-mediated thrombocytopenia in dogs. Balog, K. et al. J Vet
Intern Med 2013; 27: 536-541.
10. Treatment of 5 dogs with immune-mediated thrombocytopenia using
Romiplostim. Kohn, Barbara et al. BMC Veterinary Research 2016; 12: 96.
11. Long-term outcome of primary immune-mediated thrombocytopenia in dogs.
Simpson, K. et al. Journal of Small Animal Practice
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