|
Canine Ideopathic
Thrombocytopenia
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.
http://www.marvistavet.com/html/immune-mediated_thrombocytopen.html
http://www.homevet.com/petcare/documents/ITP.pdf#search='Ellen%20Miller%2C%20DVM%2C%20MS%20Diplomate'
Lioppincott’s Nusrsing Drug Guide, 2006
Taber’s Cyclopedic Medical Dictionary
The Merck Veterinary Manual 8th Edition
|
| this page has been viewed |
 |
times |
|
