Definition

• Immune-mediated destruction of platelets with no identifiable cause.
• In secondary IMT, infectious diseases, neoplasia, vaccination, or drugs trigger the production of antibodies.

Pathophysiology

• Antiplatelet auto-antibodies result in premature platelet destruction by macrophages mainly in the spleen by a Type II (antibody-dependent cytotoxicity) mechanism.
• In secondary IMT, platelet-bound antibodies can be antibodies bound to platelet antigens altered during course of disease or antibodies bound to foreign antigens or immune complexes.
• Auto-antibodies can be directed against megakaryocytes, thereby impeding marrow responsiveness.
• Antibody-mediated impairment of platelet function possible.
• Cause of immune dysregulation and auto-antibody production is unknown.

Systems Affected

• CNS
• GI Tract
• Ophthalmic
• Respiratory
• Skin
• Urinary

Genetics

Auto-immunity is frequently recognized in particular dog breeds and is often familial, suggesting a strong genetic influence.

Prevalence

Approximately 6% of canine and 3% of feline thrombocytopenia cases.

Signalment

Signs

Differential Diagnosis

• Measurement error due to platelet clumping; especially in cats low platelet counts often incorrect (due to tendency to aggregate/large size).
• Decreased production:
  • Infectious diseases; vaccination within the last weeks; drugs/toxins; irradiation; primary bone marrow disorders; immune-mediated response against megakaryocytes; inherited macrothrombocytopenia of Cavalier King Charles spaniels.
  • Either isolated thrombocytopenia or pancytopenia. Thrombocytopenia can be severe dependent on underlying disease.
• Increased sequestration in an enlarged spleen:
  • E.g., inflammatory disorders, neoplasias; splenic torsion.
  • Thrombocytopenia mild to moderate unless other mechanisms contribute (e.g., secondary IMT, DIC).
• Increased utilization or consumption:
  • DIC; local thrombosis; vasculitis/vascular damage with or without DIC.
  • Severe hemorrhage: may result in mild to moderate thrombocytopenia after volume resuscitation.
• Increased destruction (most common cause of severe thrombocytopenia):
  • Primary IMT.
  • Secondary IMT due to infectious diseases (anaplasmosis, ehrlichiosis, Rocky Mountain spotted fever, bartonellosis, babesiosis, leishmaniosis, dirofilariosis, angiostrongylus infection, bacterial infections; FeLV, FIV, FIP, distemper, infectious hepatitis); sterile inflammation (in cats fat tissue necrosis, etc.); neoplastic diseases (lymphoma, leukemia, hemangiosarcoma, etc.); drugs/toxins (vaccines, sulfonamides, cephalosporins, phenobarbital, NSAID); blood transfusions; SLE.

CBC/Biochemistry/Urinalysis

• Thrombocytopenia often severe (<30–40,000/µL), high risk of spontaneous bleeding; dogs and cats may be asymptomatic.
• Blood smear examination: to confirm low platelet count; to identify potential causes for secondary IMT; e.g., morulae, babesia, schistocytes, spherocytes, blast cells; anemia due to blood loss/concurrent IMHA possible.
• Leukogram can be normal; mild to moderate leukocytosis in one-third of the dogs (due to stress/inflammation), rarely leukopenia. Sometimes monocytosis, neutrophilia with/without left shift, lymphopenia, eosinophilia, eosinopenia.
• Concurrent neutropenia may indicate primary marrow disease or infectious disease.
• Coagulation testing generally normal; if abnormal consider secondary IMT, DIC and further tests.
• Chemistry results unspecific for IMT. Sometimes mildly increased liver enzymes, rarely hyperbilirubinemia due to hematoma resorption; hypoproteinemia/hypoalbuminemia due to blood loss. Hyperglobulinemia may indicate underlying disease (e.g., ehrlichiosis, leishmaniosis, FIP).
• Microscopic or macroscopic hematuria.

Other Laboratory Tests

• No gold standard immunodiagnostic test for IMT widely available. No test can distinguish between primary and secondary IMT; pIMT is a diagnosis of exclusion.
• Direct tests to detect platelet-bound antibodies have been evaluated. Flow cytometric assays performed in specialized laboratories appear to have a good sensitivity and specificity.
• Adjunct immunodiagnostic testing such as Coombs' test or antinuclear antibody titer if IMHA or SLE is suspected.
• Select other tests to exclude the above-listed differentials for thrombocytopenia (serology and/or PCR testing for infectious diseases; microbiology of urine and blood; etc.).

Imaging

• Often diffuse splenomegaly, rarely hepatomegaly.
• Radiography and ultrasonography to exclude other causes of thrombocytopenia (e.g., splenic mass) or internal bleeding.

Diagnostic Procedures

• Bone marrow evaluation not indicated if diagnosis seems straightforward and there is response to therapy within several days; indicated if concurrent neutropenia or nonregenerative anemia, atypical nucleated cells, or treatment failure.
• Number of megakaryocytes often increased, megakaryocytic hypoplasia is rare.
• Fine-needle aspiration of enlarged lymph nodes possible; no organs shall be aspirated due to high risk of severe bleeding. (Otherwise platelet products have to be available.)

Appropriate Health Care

• Uncomplicated cases with low bleeding risk and good owner compliance may be treated as outpatients.
• Patients with severe thrombocytopenia have very high risk of bleeding and warrant strict refinement (e.g., cage rest).
• Transfusion of platelet products: 10–20 mL/kg fresh whole blood, 1 unit of whole blood–derived platelet-rich plasma (ca. 8 × 10¹⁰ platelets) per 10 kg (minimum 1 unit/30 kg) in cases with critical hemorrhage. Platelets may be destroyed rapidly, but protect against catastrophic hemorrhage until specific therapy is beneficial.
• Packed red blood cells or (preferably) fresh whole blood to correct blood loss anemia.
• Management of hypovolemia with crystalloid solutions (colloids may impair platelet function).

Nursing Care

• No IM and SC injections. Apply extended pressure after IV injections and invasive procedures (e.g., lymph node aspiration). Avoid cystocentesis and jugular venipuncture. Bone marrow aspiration is safe.
• Intensive nursing care in patients with moderate to severe hemorrhage, hypovolemia, CNS signs, etc.
• Avoid hard foods.

Surgical Considerations

• High risk of bleeding in dogs with severe thrombocytopenia.
• May need extensive peri- and intraoperative (platelet) transfusions.
• Splenectomy is a (controversial) option for refractory cases not responding to medical therapy.

Drug(s)

• Corticosteroids: methyl prednisolone 10 mg/kg IV once; prednisolone (dogs 1–1.5 mg/kg q12h, cats 1.5–2 mg/kg q12h initially); dexamethasone rarely used (0.1–0.5 mg/kg q24h).
• Consider antibiotics (potential of underlying occult infection; predisposition to infection from immunoderegulation); doxycycline if tick-borne disease is not excluded.
• GI protectants (sucralfate and/or proton pump inhibitors) to prevent or treat GI ulceration.
• Other immunosuppressive agents when prednisolone fails, only controls the disease at persistently high doses, causes unacceptable side effects, and for the long-term control of refractory/relapsing cases. Most of these agents not effective in the acute management; few controlled studies available.
• Acute management-dogs: vincristine (0.02 mg/kg IV, once) or hIg (0.5 g/kg IV over 6–8h, once) in combination with prednisolone led to a more rapid increase in platelet counts compared to prednisolone alone; mycophenolate mofetil (7–10 mg/kg q12h) (onset of action unknown; successful as first-line single agent in 5 dogs); cats: hIg.
• Other immunosuppressive drugs for long-term control (initial dosages)-dogs, cyclosporine (5 mg/kg q12h), mycophenolate mofetil, azathioprine (initially 2 mg/kg q24h), leflunomide (3–4 mg/kg q24h), in combination with prednisolone; cats, chlorambucil (0.1–0.2 mg/kg q24h), mycophenolate mofetil.
• Once the platelet count is in the normal range, the initial prednisolone dose will be tapered by approximately one-fourth to one-fifth every 2 weeks, finally switching to alternate-day therapy. Taper slowly over approximately 6 months if no relapse occurs.

Precautions

• Discontinue any unnecessary medications (may have induced secondary IMT).
• Corticosteroids: GI ulceration; iatrogenic hyperadrenocorticism.
• Immunosuppression: predisposes to opportunistic infections.
• Cytotoxic medications: bone marrow suppression.
• Dose tapering too rapidly after remission may predispose to recurrence. Relapses are more difficult to control.

Patient Monitoring

• Hematocrit measurements 2–3 times daily in cases with severe hemorrhage (risk of life-threatening (GI) blood loss).
• Measure platelet count daily until >50,000/µL; then every few days until platelet counts normalize. Then every 1–3 weeks during the period of drug dose tapering.
• CBC and biochemistry every 2–4 weeks.
• Microbiological urinalysis every 4–6 weeks due to risk of secondary infections (especially in females).

Prevention/Avoidance

• Use vaccines judiciously. Role in recurrence is uncertain.
• Minimize stress that may initiate recurrence.

Possible Complications

• Excessive bleeding can be fatal; spontaneous death, e.g., due to CNS, pericardial bleeding.
• Side effects of medications (GI ulceration, Cushing habitus, opportunistic infections, bone marrow suppression).

Expected Course and Prognosis

• Platelet counts will usually increase >50,000/µL a few days after starting treatment (after 1–15, median 5 days in 24 of 25 dogs).
• Vincristin or hIg in addition to prednisolone led to a more rapid increase to 50,000/µL (median 2.5–4 days).
• Few dogs never achieve normal platelet counts.
• Failure to respond to therapy should prompt reconsideration of the diagnosis.
• 5 of 19 dogs (26%) relapsed after 19–286, median 66 days; causes for relapse were dose reduction of prednisolone, lack of owner compliance.
• If relapses occur a second immunosuppressive drug should be added, a more gradual tapering is advised, leaving the animal on an alternating daily regimen possibly for the rest of its life.
• Survival to discharge in recent studies: 84–97%; prognosis is more favorable with intensive therapy including blood/platelet products if needed.
• Mortality rate in cats is 15% (2/13).

Associated Conditions

Approximately one-third of dogs with primary IMT also have IMHA (Evans syndrome).

Synonyms

• Auto-immune thrombocytopenia
• Idiopathic/auto-immune thrombocytopenic purpura

See Also

• Anemia, Immune-Mediated
• Disseminated Intravascular Coagulation
• Thrombocytopenia

Abbreviations

• CNS = central nervous system
• DIC = disseminated intravascular coagulation
• FeLV = feline leukemia virus
• FIP = feline infectious peritonitis
• FIV = feline immunodeficiency virus
• GI = gastrointestinal
• hIg = human immunoglobulins
• IMHA = immune-mediated hemolytic anemia
• IMT = immune-mediated thrombocytopenia
• NSAID = nonsteroidal anti-inflammatory drug
• PCR = polymerase chain reaction
• pIMT = primary immune-mediated thrombocytopenia
• SLE = systemic lupus erythematosus

Client Education Handout Available Online