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Canine
Thrombocytopenia
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THE PET HEALTH LIBRARY
Immune-Mediated
Thrombocytopenia (IMT)
(Immune Destruction
of Blood Platelets)
What Is A Platelet?
A platelet is a cloud-shaped blood cell, neither related to the red
blood cell line nor the white blood cell line. Platelets act in the clotting
of blood in that they home to damaged areas of blood vessels, and aggregate
there, meaning that they pile onto each other and bind, forming a small
plug to seal the hole in the leaking blood vessel. Of course, large tears
are too big for platelets to seal and there are other blood clotting mechanisms
besides platelet aggregation but when it comes to small bleeds and normal
blood vessel wear and tear, platelets are the star of the show.
There is a saying that "platelets are vascular integrity and vascular
integrity is platelets."
A small bleed unstaunched by a platelet aggregation quickly becomes
a large bruise. Spontaneous bruising (in other words, visible bruising
from the normal wear and tear of one's body) is a sign of reduced platelet
numbers or poor platelet function.
The Life and Times of Joe Platelet
We would like to present a more detailed explanation of a platelet's
life from beginning to end. Platelets come from the bone marrow where
a large (actually gigantic, relative to the red and white blood cell precursors)
cell called a megakaryocyte splits off little active pieces of itself.
These pieces are platelets, ready to enter the circulation where they will
live for an average of 8 to 12 days (in dogs) or 6 to 8 days (in humans)
before a bleeding capillary calls them to their destiny. At any given time
some 200,000 to 500,000 platelets are on patrol in the circulation, though
only about 50,000 are considered the bare minimum to prevent spontaneous
bruising and bleeding. About 1/3 of the circulating platelets are actually
stored in the spleen, like boats in a harbor, ready to mobilize if necessary.
When platelets become too old to be useful, the spleen has cells called phagocytes
that essentially eat old cells and recycle their inner materials.
Immune-Mediated Platelet Destruction
For reasons unknown, platelets can be mistaken by the immune system
as invaders. When this happens, antibodies coat the platelets and the spleen's
phagocytes remove them in numbers up to 10 times greater than the normal
platelet removal rate. The megakaryocytes in the bone marrow respond by
getting larger and growing in numbers so that they may increase their production
of platelets. The platelets produced under these circumstances tend to
be larger and more effective than normal platelets and are called stress
platelets. The bone marrow attempts to overcome the accelerated platelet
destruction rate; unfortunately, with immune-mediated destruction occurring,
a human platelet can expect to survive only one day in the circulation
instead of its normal 6 to 8 days. If antibody levels are very high, a
platelet may survive only minutes or hours after its release from the bone
marrow and, making matters worse, antibody coated platelets still circulating
do not function normally. This is balanced by the especially effective
stress platelets entering the scene so that overall it is hard to predict
how the balance will work out in a given patient.
What Would Cause the Immune System to Get so Confused?
In many cases, a cause is never found; however, in some cases a primary
reaction in the immune system precedes the platelet destruction. For example,
immune destruction of some other stimulus could be occurring. A blood parasite,
tumor, drug, or other cell type (as in lupus or immune-mediated red cell
destruction) might all generate an antibody response. As antibodies are
produced in response to the surface shapes of the enemy cell, some of the
surface shapes may unfortunately resemble "self" shapes, such as shapes on
the surface of platelets.
What Happens to the Patient?
The usual patient is a middle-aged dog. Poodles appear to be predisposed,
though Cocker Spaniels and Old English Sheepdogs also seem to have a
higher than average incidence of this condition. Cats are rarely affected
and it is usually associated with feline leukemia.
Spontaneous bruising is the major clinical sign. The gums and oral
surfaces or the whites of the eyes are obvious areas to check, as is
the hairless area of the belly. Small spots of bruising in large conglomerations
called petechiae (pet-TEEK-ee-a) are the hallmark signs. A large, purple
expansive bruise might also be seen. This is called ecchymosis. Large
internal bleeds are not typical of platelet dysfunction, though bleeding
small amounts in urine, from the nose, or rectally may also indicate a
platelet problem.
When these sorts of signs are seen, a platelet count is drawn, along
with usually 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 if any other possible causes of low platelet count make
sense.
Other Causes of Platelet Dysfunction
Dramatic reduction in platelet numbers is almost always caused by
immune-mediated destruction, though certain tick-borne blood parasites
could also be responsible:
Ehrlichiosis (especially infection with Ehrlichia platys)
Rickettsia rickettsii (Rocky Mountain spotted fever)
Very low platelet counts can also occur in response to the suppression
of megakaryocytes within the bone marrow. This might be caused by:
Artificial estrogens
Sulfonamide antibiotics
Chloramphenicol(an antibiotic)
Chemotherapy drugs
Bone marrow cancers
Disseminated intravascular coagulation is a life-threatening disastrous
uncoupling of normal blood clotting and clot dissolving functions in the
body. One of its hallmark signs is a drop in platelet count (along with
a constellation of other signs).
If platelet numbers are normal but it is obvious that platelet function
is not, some other causes to look into might include:
Von Willebrand's disease (a hereditary clotting disorder)
Metabolic toxins (liver or kidney failure)
Overuse of aspirinor similar NSAID
Pancreatitis
methimazole(for the treatment of hyperthyroid cats)
Bone marrow cancers
Therapy for Immune Mediated Platelet Destruction
Once a tentative diagnosis of immune-mediated platelet destruction
has been made, the goal in therapy is to stop the phagocytes of the spleen
from removing the antibody-coated platelets and cutting off antibody production.
This, of course, means suppressing the immune system using whatever combination
of medication seems to work best for the individual patient.
Prednisone or Dexamethasone
These steroid hormones are the first line of defense and often are
all that is necessary to bring platelet counts back up. Unfortunately,
long-term use should be expected and this means steroid side effects
are eventually inevitable: excessive thirst, possible urinary tract infection,
panting, poor hair coat etc. The good news is that these effects should
resolve once medication is discontinued; further, if side effects are
especially problematic, other medications can be brought in to reduce the
dose of steroid needed.
Vincristine
This injectable medication is mildly immune suppressive but also
seems to stimulate a sudden burst of platelet release from the marrow
megakaryocytes. The platelets released in response to vincristine contain
a phagocyte toxin so that when spleen phagocytes ultimately eat them,
the phagocytes will die. While repeated injections of vincristine ultimately
do not yield the same effect, at least a one-time dose may be extremely
helpful. One should note that vincristine is extremely irritating if delivered
outside of the vein. It must be given IV cleanly or the overlying tissue
will slough.
Androgens
Male hormones may have some masculinizing side effects but they do
seem to cut production of anti-platelet antibodies. It also seems to synergize
with the corticosteroid hormones like prednisone and dexamethasone. Danazol
has been the androgen typically recommended in the treatment of immune-mediated
platelet destruction with weight gain being the most common side effect.
Azathioprineor Cyclophosphamide
These are stronger immune suppressive agents 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 made popular in organ transplantation,
also may be used, but expense has been problematic.
Transfusion
One might think that a transfusion of blood or at least platelet-rich
plasma might be helpful in the treatment of a platelet dysfunction. The
problem is that platelets do not survive well after removal from a blood
donor. One has about 12 hours to deliver the freshly withdrawn blood to the
recipient before the platelets become inactive. After the platelets are delivered
they are likely to live only hours. In general, most efforts are spent on
establishing immune suppression.
Gamma Globulin Transfusion
Gamma globulins are blood proteins including antibodies. Human gamma
globulin appears to occupy the phagocyte antibody-binding site so that
coated platelets cannot be grabbed out of the circulation. This has been
a promising therapy for both humans and dogs, but is generally prohibitively
expensive.
Splenectomy
If medication simply does not work or the condition keeps recurring
once medications are discontinued, the solution may be to simply remove
the spleen. After all, 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, thus in veterinary medicine it is generally
one of the last therapies invoked.
Date
Published: 4/7/2003 11:03:00 AM
Copyright
2003 - 2007 by the Veterinary Information Network, Inc. All rights reserved.
This work was originally published by Veterinary Information Network,
Inc. (VIN) and is republished with VIN's permission.
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The above information is simply informational.
It's intent is not to replace the advice of a veterinarian nor to assist you
in making a diagnosis of your pet. Please consult with your own veterinarian
for confirmation of any diagnosis. Your pets life may depend on it.