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Small animal medicine and surgery: immune mediated thrombocytopenia

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What is thrombocytopenia and most common cause of in clinics?
Spontaneous bleeding
What are clinical signs associated with thrombocytopenia?
1. Superficial bleeding with petechiae and echymoses

2. Bleeding from mucosal surfaces: epistaxis, melena, hematochezia, hematuria

3. Prolonged bleeding after venipuncture, trauma or surgery
What quick test in hospital could help you to determine if there is a thrombocytopenia?
- blood smear

- platelet numbers and morphology.
describe the process of reading a blood smear for platelets?
1. First scan the slide for platelet clumps which could result in an apparent decrease in platelet numbers elsewhere on the smear.

2. Indogs12-15 platelets should (onaverage)beineach100Xoilimmersionfield.Asa general rule, each platelet in the 100X oil immersion field represents 15,000 platelets/ul.

3. Dogs and cats will generally not spontaneously bleed due to thrombocytopenia unless their platelet count falls below 30,000 platelets/ul (2-3 platelets/oil immersion field).
at what platelet count will dogs generally spontaneously bleed?
30,000 platelets/ul (2-3 platelets/oil immersion field).
why can there be a decrease in platelets?
1. Decreased platelet production

2. Increased platelet destruction

3. Increased platelet consumption

4. Increased platelet sequestration
What are common cause for decreased platelet production in dogs?
dogs

1. bone marrow damage by a drug or toxin (estrogen, chemotherapy)

2. packing of the marrow by hematopoietic cancer cells crowding out normal marrow elements (myelophthisis).

3. Occasionally immune mediated destruction of megakaryocytes will occur so that mature platelets cannot be released from the marrow into the circulation
What are common causes for decreased platelet production?
1. FeLV-induced bone marrow hypoplasia is common.
What is the most common cause of significant thrombocytopenia and dogs?

What can cause his?
*** Immune mediated platelet destruction

- where in cats

- primary or secondary to some infections

- secondary drugs and cancers
What can cause an increase in platelet consumption?
"used up" or consumed in patients with:

1. disseminated intravascular coagulation (DIC)

2. occasionally those with vasculitis or thromboembolic disease.
How do you diagnose DIC?
thrombocytopenia

schistocytes (fragmented RBCs)

prolonged Prothrombin (PT) and Partial Thromboplastin (PTT) times

circulating fibrin degradation products (FDPs)

decreased Antithrombin 3 concentrations (AT3).
Describe platelet sequestration as a cause for thrombocytopenia?
- sequestered in an enlarged spleen, particularly if the organ is suddenly very large and engorged (as with a splenic torsion)

- Sequestration will not generally result in a platelet count low enough to cause spontaneous hemorrhage

- Numbers will be more in the 100 - 150 range with sequestration and less likely to believe

- cancer and sedation can all cause this
Is immune mediated thrombocytopenia in cats?
No
What is the typical signamlmen for IMT?
middle aged female dog. Cocker Spaniels and Old English Sheepdogs may be over-represented.
what is typically seen on a blood film in IMT?
- no platelets visible on a smear with ITP (the only disorder to do this commonly).
How do you test for suspected immune mediated thrombocytopenia
1. Perform tests to look for systemic disease

2. Rule out DIC

3. Evaluate for neoplasia

4. Bone marrow examination
What tests we perform to look for systemic disease?
CBC, Biochemistry profile, free catch urinalysis, SNAP 4DX test if endemic area for heartworm, Anaplasma or Ehrlichia).
How would you rule out DIC?

what will the tests for DAC be in a patient with IMT?
- performing a coagulation profile (PT,PTT, FDP)

- all of these tests should be normal in a patient with IMT.
How would you evaluate for neoplasia?
thoracic and abdominal radiographs and abdominal ultrasound, lymph node aspirates)
Why do you want to evaluate the bone marrow?
differentiate between decreased production of platelets and increased destruction
What should most patient's bone marrow reveal if they have IMT?
most patients with IMT there should be megakaryocytic hyperplasia in the marrow.
What is the diagnosis of thrombocytopenia based on?
EXCLUSION OF OTHER CAUSES OF THROMBOCYTOPENIA
What is the treatment of primary IMT?
1. Prednisone

2. supportive care

3. blood fusion

4. VINCRISTINE
when should you see a response to prednisone?
- Within 2 to 4 days
When do you taper? the prednisone?
- Once platelets return to normal

- halve dose every 3-4 weeks if platelets remain normal
Describe a typical regime for thrombocytopenia?
2 mg/kg bid X 3 days or until platelets are detected on a smear, then 2 mg/kg sid for 3-4 weeks, then prednisone dosages should be halved every 3-4 weeks (to 1mg/kg every day, then to 1 mg/kg every other day, then to 1⁄2 mg/kg eod, then to 1⁄4 mg/kg eod) as long as rechecks are good (normal platelet count)
Describe supportive care
IV fluids and cage rest
When would you give a blood transfusion?
- if required to maintain the patient's oxygen carrying capacity

- Sometimes transfusion with fresh whole blood or platelet rich plasma will at least temporarily stop hemorrhage in a patient with severe thrombocytopenia, even if the patient's measured platelet count does not increase.
what are the effects of Vincristine?

how often is a given? How?
- stimulates platelet release from the bone marrow, stimulates megakaryopoiesis and probably has some effects on the macrophages in the spleen and liver

- routinely recommended as a one-time therapy for patients with IMT, IV

- documented that time of hospitalization and time to normal platelet count are shorter if vincristine is administered.
Why would you want to add IMURAN? 2
- often allows more rapid tapering of the Prednisone dose

- helps to prevent relapse when the Prednisone is switched to alternate day therapy.
Did dogs tolerate long-term IMURAN welll?
- Yes most do
How might dogs be treated if they need long-term or lifelong therapy?
relatively low dose of Prednisone (0.25-0.5 mg/kg eod) together with alternate day Imuran therapy (2 mg/kg eod) forever.
Why might a splenectomy be needed?

what is the effect of the splenectomy on medical therapy for IMT?
- repeatedly relapse after responding to therapy

- Long term medical control in these patients often requires doses of Prednisone and Imuran that are not appropriate for long- term administration

- Medical therapy can actually be discontinued in over 60% of these dogs after splenectomy.
What is the prognosis for IMT?
- will have a positive response to initial immunosuppressive therapy

- Approximately 30% of dogs will die or be euthanized during the initial course of therapy

- Of the dogs that recover, approximately half will eventually be cured and off all medications, and Seth'shalf will have a recurrence requiring additional or lifelong treatment
What should you always tell the owner about IMT?
- Let them know about the prognosis, especially if you find a cause for it such as an infectious disease or lymphoma

- knowing cost will also help and affect prognosis = if the dog has a neoplasia owners may not want to pursue medical therapy