Immune-mediated thrombocytopenia

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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.

References

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