Immune Mediated Thrombocytopenia (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 assist in the clotting of blood. They aggregate in damaged areas of blood vessels,  binding together to form a small plug to seal the hole in the leaking blood vessel. They release assorted biochemicals that initiate a more permanent seal of the tear.  A small bleed unstaunched by a platelet aggregation quickly becomes a large bruise. Spontaneous bruising (in other words, visible bruising from the normal activity) is a sign of reduced platelet numbers or poor platelet function.

The Life and Times of the Platelet

Platelets come from the bone marrow where a large cell called a megakaryocyte splits off 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 a dog. At any given time some 200,000 to 500,000 platelets are on patrol in the circulatory system, though only about 20,000 to 50,000 are considered the bare minimum to prevent spontaneous bruising and bleeding. About 1/3 of the circulating platelets are stored in the spleen, ready to mobilize. When platelets become too old to be useful, the spleen has cells called phagocytes that destroy old cells and recycle their useful materials.

platelets

Immune-Mediated Platelet Destruction

For unknown reasons, 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. 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, the antibody-coated platelets still circulating do not function normally. 

 

What Would Cause the Immune System to get so Confused?

In many cases, a cause is never found; however, in most cases, a primary reaction in the immune system precedes the platelet destruction. The immune system responds to the shapes of proteins present on a cell’s surface. These shapes are similar to ID cards. The immune system recognizes shapes defined as “self” and does not attack, but when it sees a cell expressing protein shapes that are “non-self,” it will respond.

If the immune system is responding to a blood parasite, tumor, drug, or other cell types (as in lupus or immune-mediated hemolytic anemia), it will be producing antibodies against enemy shapes. Some of these shapes may, unfortunately, resemble some “self” shapes such as some of the shapes on the surface of the platelets. The platelets are then misidentified as the enemy and are attacked.

 

What Happens to the Patient?

The usual patient is a middle-aged dog. Poodles appear to be predisposed although Cocker Spaniels and Old English Sheepdogs also seem to have a higher than average incidence of this condition.

Spontaneous bruising is the major clinical sign. The gums and oral surfaces, as well as the whites of the eyes, are obvious areas to check as are the hairless area of the belly. Small spots of bruising in large conglomerations called petechiae (pet-TEEK-ee-a) are the hallmark sign. A large, purple expansive bruise might also be seen, which is called ecchymosis. Large internal bleeds are not typical of platelet dysfunction, though bleeding small amounts in urine, from the nose, mouth, or rectally may also indicate a platelet problem. Some patients will bleed into body cavities or even the lungs.

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
  • Rocky Mountain Spotted Fever

If an infectious agent such as one of these is responsible for the immune-mediated platelet destruction, specific therapy against the infection is warranted in addition to therapy for the platelet destruction.

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 cancer
  • 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 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 disease)
  • Metabolic toxins (liver or kidney failure)
  • Overuse of aspirin or 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 means the suppression of the immune system using whatever combination of medication seems to work best for the individual patient.

Sheepdog

 

Prednisone and Dexamethasone

These steroid hormones are the first line of defense. 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 the 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 they are ultimately eaten by spleen phagocytes, 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. Vincristine is extremely irritating if delivered outside of the vein. 

Azathioprine

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.

Transfusion

You might think that a transfusion of blood or at least “platelet-rich plasma” might be helpful in the treatment of platelet dysfunction. The problem is that platelets do not survive well after removal from a blood donor. You have 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.

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. The response in dogs has not been as predictably good thus in veterinary medicine it is generally one of the last therapies invoked.

Prevalence

In a study of dogs in the USA, 5.2% of dogs admitted to a specialist veterinary hospital were found to have reduced numbers of platelets. Of these dogs, 5% were diagnosed with ITP meaning it was the cause of 0.26% of hospital admissions. This suggests that it is still a fairly uncommon disease, however, it was the most likely cause of developing a very low platelet count (< 36,000,000 platelets/ml).

Outlook

The majority (>70%) of dogs with IMT (Immune-Mediated Thrombocytopenia) will show significant improvement with prednisolone alone or in combination with other immunosuppressive drugs in less than a week. After stabilization with treatment, the doses are usually slowly tapered down while monitoring closely the platelet value.

During this progressive reduction in dose, there is a risk of recurrence of the clinical signs which may be observed in around 25% of the patients. Following recurrence, treatment should be reinstituted at a higher dosage and your veterinarian will discuss further treatment options.

Unfortunately, despite appropriate treatment, around 10 to 15% of dogs with ITP can die or are euthanized at the beginning of the disease or after a recurrence of their signs. This is mainly observed with a severe disease associated with complications like coagulation disorders or severe gastrointestinal bleeding. Rapid institution of the treatment and close monitoring during hospitalization have been associated with reduced risk in dogs with ITP.

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