Immune-mediated thrombocytopaenia

Immune-mediated thrombocytopaenia.

Acquired bleeding in dogs is commonly caused by thrombocytopaenia. Binding of antibodies to the platelet surface leads to early clearance of these platelets from the circulation by the mono-nuclear phagocytic system. This condition is called primary immune-mediated thrombocytopaenia (IMT)  if other identifiable diseases are absent, and is considered to be an autoimmune disorder.

 Secondary IMT is associated with conditions such as neoplasia, infections (viral or bacterial) systemic lupus erythromatosus as well as rheumatoid arthritis. It may also be drug-associated.

Primary IMT is commonly seen in dogs. Certain breeds are predisposed e.g., cocker spaniels, old English sheepdogs, German shepherd dogs and poodles.  Middle aged females seem to be the most susceptible. Suspected triggers for primary IMT are genetics, gender, infectious agents, pollutants and stress, causing the humoral immune system to target host platelet antigens.

In secondary IMT, platelet associated antibodies may bind specifically to foreign antigens which have been absorbed onto the platelet surface. They may also bind non-specifically to form an immune complex.

Macrophages in the liver and spleen sequester these stimulated platelets at a vastly increased rate, reducing their normal half-life of about 5 days to mere hours or minutes. The spleen is an important source of anti platelet antibodies. Thrombopoiesis will often be increased in an effort to replace the sequestered platelets.

Diagnosis 

To make a diagnosis of primary IMT, other causes of thrombocytopaenia should be excluded. Consider splenomegaly, DIC, neoplasia, drug-associated and other immune-mediated thrombocytopaenia. 

Primary IMT is suspected when there is a sudden onset of symptoms of thrombocytopaenia and resulting anaemia, such as lethargy, anorexia, pallor, weakness, bruising, epistaxis, mucosal or surface bleeding, especially if preceded by a period of stress such as surgery, kenneling, oestrus or parturition. A severe platelet deficiency will be noted with a platelet count below 30 x 10⁹. This will also be obvious on a blood smear. Coagulation screening tests are often normal, though the activated clotting time may be slightly prolonged in severe cases. The buccal mucosal bleeding time is always increased. Giant platelets or megathrombocytes may be present and are indicative of enhanced thrombopoiesis. In some cases there may be suppression of bone marrow production. A stress leukogram may be seen. Concurrent haemolytic anaemia may be seen in about 20% of dogs with IMT.

Treatment

Response to corticosteroid therapy will confirm the diagnosis of IMT. Platelet count should return to normal within 7 to 10 days of starting treatment. Corticosteroids reduce the rate of macrophage induced sequestration of platelets, whether the IMT is primary or secondary. (There are no practical, readily available tests to differentiate between primary and secondary IMT.)

Glucocorticoids will also reduce antibody production, increase capillary resistance to haemorrhage and stimulate platelet production in some.  

Drugs recommended are oral prednisone or prednisolone: 2 mg/kg every 12 hours, or dexamethasone : 0.1 to 0.6 mg/kg every 24 hours.

Monitor platelet counts once a week and continue treatment until it is back to normal. Then taper the drug over the same period of time as that of the treatment. Some dogs may respond as soon as 1 week after starting treatment, but others may take several weeks. Some dogs may need to remain on treatment to prevent recurrence.

Unresponsive cases and dogs with recurrent disease may be treated with drugs such as vincristine (stimulates thrombopoiesis and reduces platelet phagocytosis by macrophages), cyclophosphamide, or by surgical removal of the spleen.

Reference:

Johnstone I. Bleeding Disorders in Dogs 2. Acquired disorders. 2002. In Practice 24:2 p67-68.