ITP – About the Condition

Description/definition:

Immune thrombocytopenia (ITP)1 is an acquired autoimmune disease defined as platelet count over 100 × 109/L2 due to destruction of platelets and in the absence of other causes of thrombocytopenia.

  • Primary ITP (not associated with an underlying disorder)
  • Secondary (associated with other diseases):
    • Autoimmune diseases:
      • Systemic lupus erythematosus (SLE)
      • Antiphospholipid syndrome (APS)
    • Viral infection:
      • HIV
      • Hepatitis C virus (HCV)
    • H. pylori
    • Drug effect
    • Lymphoproliferative disorder
    • Immune deficiency states such as common variable immune deficiency

ITP may be:

  • Newly diagnosed – within 3 months of presentation.
  • Persistent – three to 12 months since diagnosis.
  • Chronic:
    • Lasting >12 months.
    • 75% of cases of primary ITP assume a chronic course.

Severe ITP refers to ITP with bleeding symptoms sufficient to require treatment, usually associated with platelet counts < 20 x 109/L.

Pathophysiology:

An autoimmune disorder characterized by immunologic destruction of platelets occurring in response to an unknown stimulus. The pathogenesis also involves decreased platelet production.

Clinical presentation:

Patients with ITP may present:

  • Incidentally – most patients are asymptomatic at diagnosis.
  • With bleeding:
    • Mild, for example:
      • Petechiae
      • Ecchymosis
      • Oral cavity bleeding
      • Epistaxis
    • Severe:
      • Only 5% of patients reported to present with severe bleeding.
      • Intracranial hemorrhage reported in 1.4% of adults.
      • The risk of fatal bleeding is greatest in elderly patients with persistent and severe thrombocytopenia (<20 × 109/L). 
  • With fatigue and reduced health-related quality of life.

Patients with secondary ITP may also present with clinical manifestations related to the underlying disorder.

Diagnosis:

ITP is a diagnosis of exclusion. Other causes of thrombocytopenia (e.g., ethanol abuse, infection, drugs, liver disease, and primary hematologic disorders) and secondary causes of ITP should be investigated.

There is no gold-standard laboratory test for ITP. The diagnosis of ITP is primarily made by excluding nonimmune causes of thrombocytopenia and investigating potential secondary causes. The most compelling evidence supporting a diagnosis of ITP is a platelet response to ITP-specific therapy. Testing to support the diagnosis of ITP includes:

  • Suggested tests:
    • Complete blood count (CBC):
      • Usually normal except isolated thrombocytopenia, often with increased mean platelet volume (if the latter result is made available).
        • Patients with ITP always show a heterogeneous platelet population with not more than ∼30% enlarged platelets.
        • If the blood smear shows more than 60% large or even giant platelets, consider hereditary macrothrombocytopenia.
      • May show microcytic anemia (as in this case) if chronic blood loss.
    • Peripheral smear:
      • Exclude platelet clumping (pseudo-thrombocytopenia, caused by ethylenediaminetetraacetic acid-dependent platelet agglutinating antibodies).
      • Exclude microangiopathic hemolytic anemia (fragmented red cells).
      • Presence of many small or large platelets may indicate an inherited thrombocytopenia.
      • While large platelets may be found in patients with ITP, there are no high-quality data to support the use of platelet size to rule in or out a diagnosis of ITP.
    • HIV serology, regardless of individual risk factors.
    • HCV serology
    • Quantitative Ig (baseline IgG, IgA and IgM). Low levels may indicate CVID.
    • Breath test or the stool antigen test for H. pylori infection if patient has abdominal symptoms or is from an endemic region.
  • Tests that are not routinely necessary (according to clinical practice guidelines):
    • Anti-platelet antibodies – presence suggests the diagnosis, but detectable in only about 60% of patients with ITP.
    • Antinuclear antibodies (ANA)
    • Antiphospholipid antibodies
    • Thrombopoietin levels
    • Platelet parameters such as mean platelet volume
    • Bone marrow biopsy (not needed if patient presenting with typical ITP)
    • Thyroid function tests
    • Coombs test
    • Direct antiglobulin test
    • Viral PCR for EBV, CMV and parvovirus

Treatment:

Decision to treat should be based on patient’s severity of bleeding or bleeding risk, activity levels, side effects and patient preferences. In general, treatment is started in patients with newly diagnosed ITP when/if their platelets fall below 20-30 x 109/L.

The goal of ITP management in adults is to maintain a hemostatic platelet count while minimizing the toxicity of therapy.

Treatment decisions should not be dictated by the platelet count alone, but should take into account other factors, including:

  • The individual patient’s bleeding phenotype
  • The need for concomitant antithrombotic therapy or other medications that affect hemostasis
  • The need for an invasive procedure or surgery
  • Lifestyle
  • Comorbidities
  • Patient values and preferences, including a desire to participate in sports or other activities associated with bleeding risk

First-line treatment in patient with newly diagnosed ITP and a platelet count of <20-30 x 109/L includes:

Corticosteroids:

  • Prednisone 1-2 mg/kg, maximum dose 80 mg (short course < 6-8 weeks)
    • Compared with dexamethasone, greater ability to titrate therapy to match the patient’s individual response.
  • Dexamethasone 40 mg/d x 4 days, repeated up to 3 times
    • Faster responses
    • Reduced risk of dose confusion
    • No need for dose tapering, completion of therapy in four days
    • Fewer bleeding events
  • Overall effectiveness of prednisone and high-dose dexamethasone issimilar.

Use of IVIG (1 g/kg on 1 or 2 consecutive days or 0.4 g/kg per day for 5 days), or IV anti-D (50-75 mg/kg once) where available, may be appropriate in patients with bleeding, at high risk for bleeding, who require a surgical procedure, or who are unresponsive to predniso(lo)ne or who do not tolerate (or wish to avoid) glucocorticoid toxicities.

  • IVIG works more rapidly (range, 1 to 3 days) than glucocorticoids.
  • Efficacy (both short term and long term) is similar.

TPO receptor agonists (TPO-RAs) and rituximab are not considered initial therapies.

Treatment of critical bleeding includes combination of:

  • Platelet transfusions
  • Glucocorticoids (typically, pulse dexamethasone)
  • IVIG

Treatment of refractory and relapsed ITP (second and third line therapies) will be discussed in another case study.

Prognosis:

Spontaneous remissions (presumed to be independent of treatment) occur in up to 10 to 20 percent of adults with ITP.

> 75% of patients initially respond to corticosteroids, although tapering usually precipitates relapse, and ultimately only 20% to 25% of patients are able to maintain a durable platelet response after steroid discontinuation. 

Primary ITP assumes a chronic course in approximately 75% of adult patients.

Several studies have documented an increased risk of thrombosis in people with ITP compared with controls.

See case study.

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