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A rare autoimmune coagulation disorder characterized by isolated thrombocytopenia (a platelet count <100,000/microL), in the absence of any underlying disorder that may be associated with thrombocytopenia.
ORPHA:3002Classification level: Disorder
The annual incidence is estimated at between 1/25,600-37,000 in Europe, with a female to male ratio of 1.3:1. Although immune thrombocytopenia (ITP) can occur at any age, incidence shows an age-specific bimodal distribution for men with two incidence peaks observed in boys (under 18 years old) and among those older than 60 years of age.
ITP exposes to a risk of bleeding. It is defined as severe when the presence of bleeding symptoms at presentation is sufficient to warrant treatment or when the occurrence of new bleeding symptoms requires additional therapeutic intervention. It is asymptomatic in one-third of cases. Mucocutaneous hemorrhage with purpura is the most frequent clinical manifestation, usually occurring when the platelet count is below 30,000/microL. Severe visceral bleeding (hematuria, gastrointestinal hemorrhage or cerebromeningeal bleeding) is mainly observed when thrombocytopenia is below 10,000/microL and is rare, occurring mainly in elderly with comorbidities or in children in whom the disease is often self-limited; however, most children do not have severe bleeding problems despite very low platelet counts. Depending on the disease duration, ITP is classified into newly diagnosed, persistent (duration of 3-12 months) and chronic (duration of more than 12 months). Persistence or chronicity occurs in about 30 % of children compared with about 70% of adults.
The etiology is unknown. However, the disease origin is not genetic as familial cases are exceptional. Platelet destruction, mediated by autoantibodies mainly in the spleen, is associated both with impaired platelet production and with T-cell-mediated effects.
A presumptive diagnosis is made when the history, physical examination, complete blood count and examination of the peripheral blood smear do not suggest other etiologies for the thrombocytopenia. There is no `gold standard' test that can reliably establish the diagnosis. A positive response to intravenous immunoglobulin (IVIg) and/or steroids is supportive of the diagnosis. In ITP the bone marrow is normal, and bone marrow aspiration is indicated mainly in patients over 60 years' of age, in case of anomalies of other cell lines, when thrombocytopenia is refractory to first-line treatments, or when other diagnoses are suspected such as myelodysplastic syndromes (MDS). In addition to the morphologic assessment, cytogenetic testing should be considered if an MDS is suspected.
The differential diagnosis should include causes of secondary ITP (drug-induced), autoimmune diseases (such as systemic lupus erythematosus; see this term), HIV infection and hepatitis C. In elderly patients, MDS should be ruled out. In children, inherited thrombocytopenias are often misdiagnosed with ITP. ITP can be associated with genetic immunodeficiency syndromes (typically common variable immunodeficiency) and is observed mainly in children and young adults.
Management and treatment
The therapeutic strategy should be adapted both to the severity of the disease and to the patient's age. At diagnosis, children with mild or even moderate bleeding can be managed with monitoring. Treatment is rarely indicated in adults with platelet counts above 20 to 30x10exp9/L in the absence of bleeding. Corticosteroids (oral prednisone or short course of dexamethasone) are the standard first-line treatment. Use of intravenous immunoglobulins should be reserved for patients with severe bleeding (bleeding score could be used to help the physicians for IVIg indication) who are unresponsive to prednisone or for the rare patients with contra-indications to steroids. In case of chronic severe ITP, splenectomy has been used as the reference treatment for a long time. However, biologics (such as rituximab, eltrombopag, romiplostim) and even immunosuppressants (such as mycophenolate mofetil) can now be considered as an alternative to splenectomy as second-line treatment for patients refractory to first-line treatments. The respective place between these different second-line therapeutic options is still debated; ultimately, treatment should be personalized according to the patient's characteristics.
The mortality rate is generally below 2%, but may exceed 10% in the rare patients refractory to first- and second-line treatments (including splenectomy).
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