A case of immune thrombocytopenia of canine

Immune-mediated thrombocytopenia (IMT) refers to immune-mediated platelet destruction. Thrombocytopenia occurs when platelet destruction exceeds the number of platelets produced by megakaryocytes in the bone marrow.IMT is a primary or secondary disease. Primary IMT has no identifiable underlying cause of platelet destruction. Primary forms are more common in dogs than cats, although neither form is common in these species. In a study of 871 dogs with thrombocytopenia, IMT accounted for only 49 cases (5.6%). There are many potential causes of secondary IMT, These include medication, leptospirosis, Ehrlichiosis, New Ricker’s disease, Rocky Mountain spotted fever, leishmaniasis, Babesiosis, systemic mycosis, Bartontonia, hepatic zoonosis, canine empidemic virus, canine infectious hepatitis, feline infectious peritonitis, feline leukemia virus (FeLV), feline immunodeficiency virus, feline panleukopenia, bacterial infection, cystitis , pyelonephritis, primary bone marrow diseases, tumors (such as lymphoma), systemic lupus erythematosus, haemophilus mycoplasma, anaplasmosis, heartworm disease, bee poisoning, blood transfusion reactions, and other immune-mediated diseases (such as IMHA) .Note that recent vaccinations have been cited as a potential cause of IMT, but the relationship has not been fully established. In a study of 44 dogs with IMT, there was no significant difference in prevalence between the recently vaccinated patients and the control group. More research may be needed to better prove or disprove the association.

Pathophysiology
The pathogenesis of dogs and cats are not well understood. Much of what known is  inferred from a person’s IMT. The typical characteristic of IMT is the increasing of platelet autoantibodies. The destruction of platelets by MPS increased. Impaired production of megakaryocytes and platelets.The life of Platelet expectancy reduced. IMT is complex which involves B – and T-cell-mediated platelet destruction.

First,the platelet autoantibodies (i.e. major of IgG) bind to the surface of the platelet, causing MPS to destroy healthy platelets. This process is mediated by platelet coating by macrophage Fc receptor binding antibodies. T cells also contribute to platelet destruction, primarily Th1 and Th17 immune responses. The immune regulation that maintains self-tolerance (such as T and B regulatory cells) is also usually abnormal, leading to the persistence of anti-platelet immune responses.

The circulating platelet life of IMT patients is usually less than 1 day. The spleen is the main site of immune-mediated platelet destruction, with a destruction rates up to ten times that normal, senescent platelet consumption. Because antibody-bound platelets are cleared by MPS and not by the liver, liver TPO release is not triggered, thus slowing the rate of platelet reproduction.

Bone marrow accelerates platelet destruction by increasing the number of megakaryocytes. Thrombosis can increase to five times the normal rate. In IMT patients, however, platelet autoantibodies (in addition to unreleased TPO) cross-react with megakaryocytes, and thrombogenesis is often further weakened. Patients with IMT may develop megakaryocyte thrombocytopenia (i.e. megakaryocyte hypoplasia) secondary to immune-mediated destruction of megakaryocytes, although this is uncommon.

It is also worth noting that in canine patients with IMT, circulating autoantibodies may cause platelet dysfunction (i.e., thromboembolism) in addition to destroying platelets. However, studies have shown that surviving circulating platelets often have normal or enhanced ability to stop bleeding, possibly due to the large number of megaloplatelets (i.e., large young platelets). It is not known if these problems also apply to cats with IMT.

Prevalence and Signalment
Immune-mediated thrombocytopenia accounts for about 5-15% of canine thrombocytopenia cases. In a study of 61 thrombocytopenic dogs, 57% were diagnosed with primary IMT and 28% with secondary IMT (i.e. 9.8% lymphatic/medullary tumor, 9.8% infection, 5% liver disease, and 3% drug exposure). The sex tendency of IMT is at least twice as common in female as in male. Representative breeds include cocker spaniel, miniature poodle, toy poodle and Old English Shepherd. Genetic factors, combined with etiological triggers (e.g., environment, infection), have been theorized as potentially susceptible varieties, but more research is needed. Middle-aged dogs are most affected.

Clinical Signs
Some patients are asymptomatic. Most clinical symptoms occur with an increased tendency to bleed. Possible clinical symptoms include lethargy, anorexia, fever, weakness, petechiae, ecchymosis, pale mucous membranes, bleeding gums, blackness, hematemesis, blood in the stool, nosebleed, hematuria, hyphema, sclera or iris bleeding, retinal bleeding, blindness, frontal signs, altered mental status, epilepsy, lymphadenopathy, enlargement of the liver, enlargement of the spleen, lameness, cough, dyspnea, and hematoma formation.

Monitoring and prognosis
Reported that the platelet count in CBC should be monitored daily until platelets exceeded 50,000/µL. Then followed by weekly monitoring until platelet counts normalized. Within 7-10 days of starting glucocorticoids, the platelet count usually increases to 50-100,000 /µL. Immunosuppressive therapy can be tapered over 4-6 months once platelet counts return to normal. According to the general guideline，the standard is to reduce the dose by 20-25% every 2-3 weeks once the platelets are confirmed to be stable. Platelet counts were monitored every 1-2 weeks during the drug reduction period. One study reported that 16 primary IMT dogs received a median dose of prednisolone of 2.4 mg/kg/ day in remission and 0.9 mg/kg/ day in relapse. Prednisolone reduction rates were significantly higher in patients with acute recurrence (i.e., remission <60 days) compared to patients with delayed recurrence or no recurrence.If IMT is treated quickly and appropriately, the prognosis is usually good. Reported survival rates range from 70-90%. Relapse is possible (i.e. 9-58%), and some patients require long-term maintenance therapy. IMT can lead to death and is usually secondary to bleeding. Secondary infections caused by immunosuppression are also a concern. In a study of 73 dogs with primary IMT, 61/73 survived to discharge. The presence of melanoemia or elevated BUN on admission was associated with reduced survival. Another study of 30 dogs reported that 29/30 dogs survived at least 14 days after the onset of symptoms, with 27 dogs surviving 15-1684 days after the onset of symptoms (median 220 days). Another study of 46 dogs with primary IMT reported a survival to discharge rate of 73 percent, with an average hospital stay of 5.1 days. Of those who survived, 39 percent experienced a relapse. Treatment options include corticosteroids or glucocorticoids in combination with other drugs (e.g. Azathioprine, cyclosporine, vincristine). There is no significant difference between protocol and survival. Another study reported that patients with megakaryocyte thrombocytopenia had more severe anemia.The increased of clinical symptoms of bleeding.The number of transfusions required increased compared to dogs with primary peripheral IMT. In this study, 29 out of 34 primary IMTs survived to discharge, but only 1 out of 7 megakaryocytocytopenia survived to discharge.