Immune-mediated thrombocytopenia

From Dog
Pale mucous membranes in a Cocker Spaniel with immune-mediated thrombocytopenia[1]
Petechiae caused by immune-mediated thrombocytopenia[2]

Immune-mediated thrombocytopenia is a rare immune-mediated hematological disease of dogs characterized by low circulating levels of thrombocytes (platelets) (<2 x 1011/L) resulting in bleeding episodes.

In this disease, thrombocytopenia arises from increased destruction of platelets (as opposed to consumption coagulopathies)[3] due to production of platelet-binding immunoglobulins directed against platelet-surface antigens by macrophages or T-lymphocytes[4]. With immune mediated thrombocytopenia, there is an increase in platelet antibodies that bind to platelet membranes. The antibody-platelet cause increased destruction of platelets by the mononuclear phagocytic system within the spleen. Ultimately, thrombocytopenia develops when destruction of platelets exceeds platelet production by megakaryocytes in the bone marrow[5].

The Cocker Spaniel[6] and Cavalier King Charles Spaniel appear to be predisposed to this condition.

Immune-mediated thrombocytopenia may occur as a primary disease (primary immune-mediated thrombocytopenia or idiopathic thrombocytopenic purpura)[7] or as a secondary disease due to other underlying conditions which induce autoimmunity. The mechanism by which secondary immune-mediated thrombocytopenia occurs is thought to involve a variety of immunological mechanisms such as molecular mimicry or the induction or alteration of host antigens[8].

Primary disease which can induce a secondary immune-mediated thrombocytopenia include:

- Dirofilaria immitis[9], Angiostrongylus vasorum[10][11], Rickettsia spp, Leishmania infantum[12], Ehrlichia canis[13], Borrelia burgdorferi, Babesia rossi[14], Anaplasma phagocytophilum[15]

Clinical symptoms associated with this condition include lethargy, fever, melena, hematemesis, hematuria, hematochezia, epistaxis and mucosal petechiations or ecchymotic hemorrhages on the mucous membranes. Many of these symptoms are referable to underlying thromboembolism and/or hemorrhagic episodes[25]. Spontaneous hemorrhage does not typically occur unless platelets are less than 50,000 and some dogs, buccal mucosal bleeding times may be normal.

Hematological analysis usually reveals reduced thrombocyte numbers and elevated partial thromboplastin time (normal = 9.6–13.8) and prothrombin time (normal = 7.5–9.9)[26]. Macrothrombocytes and fusiform cytoplasmic inclusion bodies in neutrophils may be observed in some cases (May-Hegglin anomaly).

The diagnosis of immune-mediated thrombocytopenia is made by the exclusion of the secondary causes of thrombocytopenia. Bone marrow cytological analysis should be performed to assess appropriate cellularity within the bone marrow to exclude evidence of granulocytic and megakaryocytic hyperplasia, infectious agents or neoplastic cells.

Therapy may require intravenous fresh frozen plasma in acute cases and use of glucocorticoids at an immunosuppressive dose, cyclosporine or azathioprine. The use of adjunct therapies such as human intravenous immunoglobulin as a single dose have significantly reduced recovery times in some dogs and should be considered where financial constraints are not problematic[27].

Patients should be monitored for side effects including hepatotoxicity and pancytopenia. Primary immune-mediated thrombocytopenia signs usually resolve within 2-5 days of initiation of therapy. Refractory cases can be treated with vincristine every 7 days to increase platelets. Once platelet counts have normalized, decrease the glucocorticoid every 2-3 weeks while monitoring the platelet count and to reach a lowest effective dose.

Although this is a serious disease, about 60 - 70% of patients respond to long-term therapy, the remainder usually succumbing to illness within 3 months[28]. The presence of melena or high BUN concentration in the study suggested a poor prognosis for affected dogs.


  1. Pet Place
  2. King Edward Vet
  3. Davenport DJ et al (1982) Platelet disorders in the dog and cat Part I: Physiology and Pathogenesis. J Cont Educa Pract Vet 4:762–772
  4. Whitley NT & Day MJ (2011) Immunomodulatory drugs and their application to the management of canine immune-mediated disease. J Small Anim Pract 52(2):70-85
  6. O'Marra SK et al (2011) Treatment and predictors of outcome in dogs with immune-mediated thrombocytopenia. J Am Vet Med Assoc 238(3):346-352
  7. Lewis DC & Meyers KM (1996) Canine idiopathic thrombocytopenic purpura. Journal of Veterinary Internal Medicine. 10':207–218
  8. Day MJ (1999) In: Clinical Immunology of the Dog and Cat. Day MJ, editor. London: Manson Publishing Ltd. The basis of immune-mediated disease; pp:61–65
  9. Grindem CB et al (1991) Epidemiologic survey of thrombocytopenia in dogs: a report on 987 cases. Vet Clin Path 20:38–43
  10. Gould SM & McInnes EL (1999) Immune-mediated thrombocytopenia associated with Angiostrongylus vasorum infection in a dog. Journal of Small Animal Practice 40:227–232
  11. O'neill E et al (2010) Immune-mediated thrombocytopenia associated with angiostrongylus vasorum infection in a Jack Russell terrier. Ir Vet J 63(7):434-440
  12. Cortese L et al (2009) Secondary immune-mediated thrombocytopenia in dogs naturally infected by Leishmania infantum. Vet Rec 164(25):778-782
  13. Giudice E et al (2010) Effect of desmopressin on immune-mediated haemorrhagic disorders due to canine monocytic ehrlichiosis: a preliminary study. J Vet Pharmacol Ther 33(6):610-614
  14. Scheepers E et al (2011) Serial haematology results in transfused and non-transfused dogs naturally infected with Babesia rossi. J S Afr Vet Assoc 82(3):136-143
  15. Cockwill KR et al (2009) Granulocytic anaplasmosis in three dogs from Saskatoon, Saskatchewan. Can Vet J 50:835–840
  16. Schnier LM (2010) A case of splenic torsion with progressive anemia and thrombocytopenia. Can Vet J 51(5):527-529
  17. Snead E et al (2011) Glucocorticoid-dependent hypoadrenocorticism with thrombocytopenia and neutropenia mimicking sepsis in a Labrador retriever dog. Can Vet J 52(10):1129-1134
  18. Botsch V et al (2009) Retrospective study of 871 dogs with thrombocytopenia. Vet Rec 164(21):647-651
  19. Brown MR & Rogers KS (2001) Neutropenia in dogs and cats: A retrospective study of 261 cases. J Am Anim Hosp Assoc 37:131–139
  20. Orcutt ES et al (2010) Immune-mediated hemolytic anemia and severe thrombocytopenia in dogs: 12 cases (2001-2008). J Vet Emerg Crit Care (San Antonio) 20(3):338-345
  21. Joshi BC & Jain NC (1977) Experimental immunologic thrombocytopenia in dogs: a study of thrombocytopenia and megakaryocytopoiesis. Res Vet Sci 22:11–17
  22. Trepanier LA et al (2003) Clinical findings in 40 dogs with hypersensitivity associated with administration of potentiated sulfonamides. J Vet Int Med 17:647–652
  23. Huang AA et al (2012) Idiopathic immune-mediated thrombocytopenia and recent vaccination in dogs. J Vet Intern Med 26(1):142-148
  24. Flatland B et al (2011) May-Hegglin anomaly in a dog. Vet Clin Pathol 40(2):207-214
  25. O'Marra SK et al (2012) Investigating hypercoagulability during treatment for immune-mediated thrombocytopenia: a pilot study. J Vet Emerg Crit Care (San Antonio) 22(1):126-130
  26. Dircks B et al (2011) Clinical and laboratory-diagnosed parameters in 21 dogs with primary immune-mediated thrombocytopenia. Tierarztl Prax Ausg K Kleintiere Heimtiere 39(1):17-24
  27. Bianco D et al (2009) A prospective, randomized, double-blinded, placebo-controlled study of human intravenous immunoglobulin for the acute management of presumptive primary immune-mediated thrombocytopenia in dogs. J Vet Intern Med 23(5):1071-1078
  28. Ishihara M et al (2010) Evaluation of prognostic factors and establishment of a prognostic scoring system for canine primary immune-mediated hemolytic anemia. J Vet Med Sci 72(4):465-470