Vaccine administration. Canine postvaccinal immune-mediated thrombocytopenia has been suspected, but evidence of a direct causative role of vaccines in immune-mediated thrombocytopenia is lacking.¹

Neoplasia. Thrombocytopenia is commonly associated with various hematopoietic and solid neoplasms, including lymphoma, mammary adenocarcinoma, mast cell tumor, hemangiosarcoma, nasal adenocarcinoma, and fibrosarcoma.^1,9 Antibody against tumor antigens that are closely related to platelet membranes may initiate platelet destruction. In some dogs with solid neoplasms, thrombocytopenia resolves after tumor remission.¹

Infectious agents. Viral, bacterial, rickettsial, protozoal, and parasitic infections may also play a role in inducing immune-mediated thrombocytopenia.² Infections may result in immune-mediated platelet destruction by exposing antigenic sites on platelet surfaces or through immune-complex injury to platelet membranes.⁷ Antibodies that can bind to platelets have been identified in dogs with ehrlichiosis, babesiosis, leishmaniasis, and dirofilariasis.^2,7,10 The pathogenesis of thrombocytopenia with several infectious diseases is multifactorial, involving decreased production by the bone marrow and splenic sequestration, in addition to immune-mediated destruction.⁸

When evaluating a patient with suspected immune-mediated thrombocytopenia, be sure to exclude non-immune-mediated causes. Other mechanisms of thrombocytopenia include decreased platelet production due to bone marrow disorders, platelet sequestration, non-immune-mediated platelet destruction, platelet consumption, and platelet loss. The cause of thrombocytopenia may be multifactorial.

Neoplasia may cause thrombocytopenia through immune-mediated and non-immune-mediated mechanisms. Non-immune-mediated mechanisms include platelet consumption, splenic sequestration, hemorrhage, myelophthisis, and bone marrow suppression by chemotherapy or radiation.^2,8

Hemolytic uremic syndrome, a rare cause of thrombocytopenia, is readily differentiated based on renal failure, microangiopathic hemolytic anemia, and fever.² Decreases in platelet number resulting from splenic sequestration are generally modest.² Similarly, thrombocytopenia resulting from blood loss is generally mild and transient, although moderate to severe thrombocytopenia has been reported with anticoagulant rodenticide intoxication.^8,11 Immune-mediated thrombocytopenia usually causes severe thrombocytopenia—often < 50,000 platelets/μl.¹

A severe, inherited thrombocytopenia has been reported to occur in up to 50% of Cavalier King Charles spaniels.¹² Platelet counts can be as low as 20,000/μl, but many affected dogs have macrothrombocytes, and this disorder is not associated with a bleeding tendency. Perform manual platelet counts in dogs of this breed with thrombocytopenia, as large platelets may result in falsely low platelet counts as measured by impedance analyzers.

Bone marrow disorders can cause thrombocytopenia, but if thrombocytopenia is the sole abnormality on a complete blood count (CBC), bone marrow disorders are unlikely. With the exception of early estrogen toxicity, bone marrow disorders that cause thrombocytopenia typically cause concurrent leukopenia, with or without anemia.^1,2 The presence of a marked, nonregenerative anemia or neutropenia could suggest bone marrow disease; alternatively these findings may be seen with immune-mediated disease.

DIAGNOSTIC APPROACH

Signalment

Middle-aged dogs are most commonly affected by immune-mediated thrombocytopenia, but the disease can occur in dogs of any age. A high prevalence has been reported in miniature, toy, and standard poodles; cocker spaniels; Old English sheepdogs; and German shepherds, but any breed, including crossbreeds, may be affected.^1,2,6 The high prevalence in some breeds may suggest a genetic predisposition. Although dogs of either sex may develop immune-mediated thrombocytopenia, about twice as many female dogs are affected compared with male dogs.^1,2