by Nancy McDonald RN, BSN
Thrombocytopenia means not enough blood platelets are circulating in the blood. Causes of thrombocytopenia can be grouped into four areas: accelerated platelet destruction, increased platelet consumption, sequestration, and decreased bone marrow production. Immune-mediated thrombocytopenia (IMP) is accelerated platelet destruction. Other names are Canine Ideopathic Thrombocytopenia and Ideopathic Thrombocytopenia (ITP).
Platelets act in clotting of blood by migrating to damaged areas of blood vessels and “aggregating” there, meaning that they pile onto each other and bind, forming a small plug to seal the hole in the leaking blood vessel. Large tears require other blood clotting mechanisms to come into play besides platelet aggregation, but small bleeds and normal wear and tear are the platelets specialty.
Platelets are produced in the bone marrow from pieces of a large cell called a megakaryocyte. Platelets are neither a red or white blood cell, only a close relative. Platelets circulate in the dog an average of 8 to 12 days waiting to aid a bleeding capillary (a tiny blood vessel). About 1/3 of the circulating platelets are stored in the spleen, ready for use if needed. When platelets become too old, they are destroyed by cells called “phagocytes”, and their inner materials are recycled.
The task of the body’s immune system is to fight foreign substances in the body, like germs and viruses. In autoimmune disease, the immune system produces antibodies that attack the body’s own healthy tissues. For unknown reasons with immune-mediated thrombocytopenia, the branch of the immune system that produces antibodies begins to direct them against the patient’s platelets. Platelets become quickly coated with tiny antibody proteins, essentially marking these platelets for destruction. The spleen’s phagocytes remove these normal platelets at a rate up to 10 times the normal. In addition, a special protein system, called the “complement system”, is activated by these antibodies. Complement proteins are able to simply rupture platelets if they are adequately coated with antibodies. The bone marrow tries to compensate for the platelet destruction by increased production of larger and more effective platelets. However, in immune-mediated thrombocytopenia, a platelet may survive only a day or two or if antibody levels are very high, only a matter of minutes.
In many cases, the cause of immune-mediated thrombocytopenia is never known. Genetic and environmental factors probably play a role in the development of the disease in individual animals. Certain breeds, notably Poodles, Old English Sheep Dogs, and Cocker Spaniels develop IMT; females outnumber males almost 2:1; the median age of affected dogs is 6 years. Environmental factors such as physical or emotional stress, exposure to drugs or chemicals, and exposure to infectious agents can act as triggers to set off a reaction causing platelet destruction.
Primary immune-mediated thrombocytopenia can occur alone or with other disorders, immune-mediated hemolytic anemia or systemic lupus erythematosus, as the mechanism of each of these is true autoimmunity. IMT associated with neoplasia (cancers) and infectious diseases (Ehrlichia, Rocky Mountain Spotted Fever, Histoplasma), drugs (methimazole, quinidine, penicillin, sulfonamides, estrogen, chloramphenicol) and vaccinations with modified-live viruses (especially canine distemper virus) is considered secondary immune-mediated thrombocytopenia.
Historical findings in a patient with IMP are an acute onset of lethargy, weakness, decreased appetite and various bruising and bleeding. Spontaneous bruising is the major clinical sign. Small spots of bruising in large conglomerations called “petecchiae” are the hallmark sign. A large, purple expansive bruise called “ecchymosis” may be seen. Bleeding may be severe although large internal bleeds are not typical of platelet dysfunction. Gums and oral surfaces or whites of the eyes are areas to check as well as the hairless areas of the abdomen. Blood in the urine, from the nose or rectally may also indicate platelet problems.
When symptoms are seen, a platelet count is drawn, along with an array of clotting parameters, red blood cell counts to assess blood loss, and other general metabolic blood tests. Since testing to detect actual anti-platelet antibodies is not available, the veterinarian must determine other possible causes of low platelet count besides IMT. These considerations are increased platelet consumption (severe hemorrhage, disseminated intravascular coagulopathy, vasculitis, hemolytic-uremic syndrome), sequestration (splenomegaly, sepsis, splenic torsion), decreased bone marrow production (myeloproliferative disorder, neoplasia in the bone marrow, drug reaction, chronic Ehrlichios, idiopathic aplasia).
Once a tentative diagnosis of immune-mediated thrombocytopenia has been made, the goal of therapy is to correct an underlying condition (if there is one) and simultaneously treat the platelet destruction. The treatment of IMT relies on suppressing the immune system’s attack against platelets using whatever combination of medications that work best for the individual patient.
The medication most commonly prescribed to shut off the immune system is a steroid hormone called prednisone. Many times this is all that is necessary to bring platelet counts back up. However, it takes a period of months to effectively treat and then slowly reduce the prednisone dosage. Unfortunately, long-term steroid use means side effects (excessive thirst, possible urinary tract infection, panting, poor hair coat, bloating, increased appetite) are eventually inevitable. Fortunately, these side effects should resolve once the medication is discontinued.
Therapy must be continued until there is laboratory evidence that platelet destruction has stopped. If side effects of steroid therapy are especially problematic or if a patient is non-responsive to prednisone alone, other medications can be added. Vincristine is an injectable medication, mildly immune suppressive, but also stimulates a release of platelets from the bone marrow megakaryocytes. Also, in response to the vincristine, the platelets released contain a phagocyte toxin that when phagocytes eat the platelets, the phagocytes die. Repeated injections of vincristine do not yield the same results, but one dose may be extremely helpful.
Androgens, male hormones, seem to have a synergizing effect with steroid hormones like prednisone and dexamethasome. Weight gain is the most common side effect.
There are stronger immune suppressive agents (cytoxan, imuran) typically used in cancer chemotherapy. If steroid side effects are unacceptable or if the patient does not respond to steroids alone, one of these medications may be indicated. Cyclosporine, a newer medication used in organ transplantation, also may be used, but the cost can be a problem.
Human gamma globulin (blood proteins including antibodies) prevents phagocytes from grabbing antigen-coated platelets out of circulation. This is a promising therapy but is generally prohibitively expensive.
Transfusions are not necessarily helpful in platelet destruction because platelets from plasma do not survive very long. However, if a dog’s platelet count is less than 50,000 (the normal is 200,000 – 500,000), hospitalization is recommended and a transfusion may be given to buy time for immuno-suppression therapy to become effective.
If medication simply does not work or the condition keeps recurring once medications are discontinued, the solution may be to remove the spleen because this is where the phagocytes removing the platelets are primarily located. In humans, immune-mediated platelet destruction is generally treated with splenectomy first. Response in dogs has not been as predictably good, so generally, it is one of the last therapies.
Prognosis is highly variable and depends on the underlying cause if one is present, complications related to the disease or drug therapy, and the response to treatment. Relapses can occur months to years after the initial episode. However, if your pet responds to therapy, prognosis is generally good.
Lioppincott’s Nusrsing Drug Guide, 2006
Taber’s Cyclopedic Medical Dictionary
The Merck Veterinary Manual 8th Edition