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The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia

Cindy Neunert, Wendy Lim, Mark Crowther, Alan Cohen, Lawrence Solberg Jr and Mark A. Crowther

Data supplements

  • Supplemental materials for: Neunert et al

    Persons who provided an assessment of the article prior to submission to the journal:
    Dr. Steven Allen
    Dr. George Buchanan
    Dr. Elaine Chottiner
    Prof. Michael Greaves
    Dr. Tim McCavit
    Dr. Keith McCrae
    Dr. Vincent Picozzi
    Dr. Douglas Rizzo
    Dr. Francesco Rodeghiero
    Dr. Roberto Stasi
    Dr. Bob Weinstein
    Dr. Dan Vogl

    Files in this Data Supplement:

Article Figures & Data

Tables

  • Table 1

    Summary of recommendations

    Section 1: ITP in children
    Case 1: newly diagnosed ITP in children
    Diagnosis of ITP
        1.1.A. We recommend:
    • Bone marrow examination is unnecessary in children and adolescents with the typical features of ITP (grade 1B).

    • Bone marrow examination is not necessary in children who fail IVIg therapy (grade 1B).

        1.1.B. We suggest:
    • Bone marrow examination is also not necessary in similar patients prior to initiation of treatment with corticosteroids or before splenectomy (grade 2C).

    • Testing for antinuclear antibodies is not necessary in the evaluation of children and adolescents with suspected ITP (grade 2C)

    Initial management of ITP
        1.2.A. We recommend:
    • Children with no bleeding or mild bleeding (defined as skin manifestations only, such as bruising and petechiae) be managed with observation alone regardless of platelet count (grade 1B).

    Initial pharmacologic management of pediatric ITP
        1.3.A. We recommend:
    • For pediatric patients requiring treatment, a single dose of IVIg (0.8-1 g/kg) or a short course of corticosteroids be used as first-line treatment (grade 1B).

    • IVIg can be used if a more rapid increase in the platelet count is desired (grade 1B).

    • Anti-D therapy is not advised in children with a hemoglobin concentration that is decreased due to bleeding, or with evidence of autoimmune hemolysis (grade 1C).

        1.3.B. We suggest:
    • A single dose of anti-D can be used as first-line treatment in Rh-positive, nonsplenectomized children requiring treatment (grade 2B).

    Case 2: children who are treatment nonresponders
    Appropriate second-line treatments for pediatric ITP
        2.1.A. We suggest:
    • Rituximab be considered for children or adolescents with ITP who have significant ongoing bleeding despite treatment with IVIg, anti-D, or conventional doses of corticosteroids (grade 2C).

    • Rituximab may also be considered as an alternative to splenectomy in children and adolescents with chronic ITP or in patients who do not respond favorably to splenectomy (grade 2C).

    • High-dose dexamethasone may be considered for children or adolescents with ITP who have significant ongoing bleeding despite treatment with IVIg, anti-D, or conventional doses of corticosteroids (grade 2C).

    • High-dose dexamethasone may also be considered as an alternative to splenectomy in children and adolescents with chronic ITP or in patients who do not respond favorably to splenectomy (grade 2C).

    Splenectomy for persistent or chronic ITP or ITP unresponsive to initial measures
        2.2.A. We recommend:
    • Splenectomy for children and adolescents with chronic or persistent ITP who have significant or persistent bleeding, and lack of responsiveness or intolerance of other therapies such as corticosteroids, IVIg, and anti-D, and/or who have a need for improved quality of life (grade 1B).

        2.2.B. We suggest:
    • Splenectomy or other interventions with potentially serious complications be delayed for at least 12 months, unless accompanied by severe disease defined by the International Working Group as unresponsive to other measures or other quality of life considerations (grade 2C).

    H pylori testing in children with persistent or chronic ITP
        2.3.A. We recommend:
    • Against routine testing for H pylori in children with chronic ITP (grade 1B).

    Case 3: management of MMR-associated ITP
        3.1.A. We recommend:
    • Children with a history of ITP who are unimmunized receive their scheduled first MMR vaccine (grade 1B).

    • In children with either nonvaccine or vaccine-related ITP who have already received their first dose of MMR vaccine, vaccine titers can be checked. If the child displays full immunity (90%-95% of children), then no further MMR vaccine should be given. If the child does not have adequate immunity, then the child should be re-immunized with MMR vaccine at the recommended age (grade 1B).

    Section 2: ITP in the adult
    Case 4: newly diagnosed ITP in the adult
    Initial diagnosis of ITP
        4.1.A. We recommend:
    • Testing patients for HCV and HIV (grade 1B).

        4.1.B. We suggest:
    • Further investigations if there are abnormalities (other than thrombocytopenia and perhaps findings of iron deficiency) in the blood count or smear (grade 2C).

    • A bone marrow examination is not necessary irrespective of age in patients presenting with typical ITP (grade 2C).

    Treatment of newly diagnosed adult ITP
        4.2.A. We suggest:
    • Treatment be administered for newly diagnosed patients with a platelet count < 30 × 109/L (grade 2C).

    First-line treatment of adult ITP
        4.3.A. We suggest:
    • Longer courses of corticosteroids are preferred over shorter courses of corticosteroids or IVIg as first-line treatment (grade 2B).

    • IVIg be used with corticosteroids when a more rapid increase in platelet count is required (grade 2B).

    • Either IVIg or anti-D (in appropriate patients) be used as a first-line treatment if corticosteroids are contraindicated (grade 2C).

    • If IVIg is used, the dose should initially be 1 g/kg as a one-time dose. This dosage may be repeated if necessary (grade 2B).

    Treatment of patients who are unresponsive to or relapse after initial corticosteroid therapy
        4.4.A. We recommend:
    • Splenectomy for patients who have failed corticosteroid therapy (grade 1B).

    • Thrombopoietin receptor agonists for patients at risk of bleeding who relapse after splenectomy or who have a contraindication to splenectomy and who have failed at least one other therapy (grade 1B).

        4.4.B. We suggest:
    • Thrombopoietin receptor agonists may be considered for patients at risk of bleeding who have failed one line of therapy such as corticosteroids or IVIg and who have not had splenectomy (grade 2C).

    • Rituximab may be considered for patients at risk of bleeding who have failed one line of therapy such as corticosteroids, IVIg, or splenectomy (grade 2C).

    Laparoscopic versus open splenectomy and vaccination prior to splenectomy
        4.5.A. We recommend:
    • That for medically suitable patients, both laparoscopic and open splenectomy offer similar efficacy (grade 1C).

    Case 5: treatment of adult ITP after splenectomy
    Treatment of ITP after splenectomy
        5.1.A. We recommend:
    • Against further treatment in asymptomatic patients after splenectomy who have platelet counts > 30 × 109/L (grade 1C).

    Case 6: treatment of ITP in pregnancy
    Management of ITP during pregnancy
        6.1.A. We recommend:
    • Pregnant patients requiring treatment receive either corticosteroids or IVIg (grade 1C).

    Treatment of ITP during labor and delivery
        6.2.A. We suggest:
    • For pregnant women with ITP, the mode of delivery should be based on obstetric indications (grade 2C).

    Case 7: treatment of specific forms of secondary ITP
    Management of secondary ITP, HCV-associated
        7.1.A. We suggest:
    • In patients with secondary ITP due to HCV infection, antiviral therapy should be considered in the absence of contraindications (grade 2C). However, the platelet count should be closely monitored due to a risk of worsening thrombocytopenia attributable to interferon.

    • If treatment for ITP is required, the initial treatment should be IVIg (grade 2C).

    Management of secondary ITP, HIV-associated
        7.2.A. We recommend:
    • For patients with secondary ITP due to HIV, treatment of the HIV infection with antiviral therapy should be considered before other treatment options unless the patient has clinical significant bleeding complications (grade 1A).

    • If treatment for ITP is required, initial treatment should consist of corticosteroids, IVIg, or anti-D (grade 2C) and splenectomy in preference to other agents in symptomatic patients who fail corticosteroids, IVIg, or anti-D (grade 2C).

    Management of secondary ITP, H pylori–associated
        7.3.A. We recommend:
    • That eradication therapy be administered in patients who are found to have H pylori infection (based on urea breath tests, stool antigen tests, or endoscopic biopsies) (grade 1B).

        7.3.B. We suggest:
    • Screening for H pylori be considered in patients with ITP in whom eradication therapy would be used if testing is positive (grade 2C).

    • ITP indicates immune thrombocytopenia; IVIg, intravenous immunoglobulin; anti-D, anti-D immunoglobulin; MMR, measles-mumps-rubella; HCV, hepatitis C virus; HIV, human immunodeficiency virus; and H pylori, Helicobacter pylori.

  • Table 2

    Causes of secondary ITP

    • Antiphospholipid syndrome

    • Autoimmune thrombocytopenia (eg, Evans syndrome)

    • Common variable immune deficiency

    • Drug administration side effect

    • Infection with cytomegalovirus, Helicobacter pylori, hepatitis C, human immunodeficiency virus, varicella zoster

    • Lymphoproliferative disorders

    • Bone marrow transplantation side effect

    • Vaccination side effect

    • Systemic lupus erythematosus

    • Evans syndrome is associated with autoimmune thrombocytopenia with coincident hemolytic anemia.

  • Table 3

    Definitions of response to treatment by ITP*

    Complete response (CR)A platelet count ≥ 100 × 109/L measured on 2 occasions > 7 days apart and the absence of bleeding.
    Response (R)A platelet count ≥ 30 × 109/L and a greater than 2-fold increase in platelet count from baseline measured on 2 occasions > 7 days apart and the absence of bleeding.
    No response (NR)A platelet count < 30 × 109/L or a less than 2-fold increase in platelet count from baseline or the presence of bleeding. Platelet count must be measured on 2 occasions more than a day apart.
    Loss of complete responseA platelet count < 100 × 109/L measured on 2 occasions more than a day apart and/or the presence of bleeding.
    Loss of responseA platelet count < 30 × 109/L or a less than 2-fold increase in platelet count from baseline or the presence of bleeding. Platelet count must be measured on 2 occasions more than a day apart.
    • * Based on the recommendations of the International Working Group.7

  • Table 4

    Definitions of time to and duration of response, and the time to initial and peak response for different ITP treatments*

    Time to responseFrom start of treatment until either complete response or response
    Duration of responseTime from complete response or response until loss of complete response or response Measured as the proportion of the cumulative time spent in complete response or response during the period under examination as well as the total time observed from which the proportion is derived
    Expected time to responseTreatment typeInitial response, daysPeak response, days
    Anti-D1-33-7
    Azathioprine30-9030-180
    Danazol14-9028-180
    Dexamethasone2-144-28
    Eltrombopag7-2814-90
    IVIg1-32-7
    Prednisone4-147-28
    Rituximab7-5614-180
    Romiplostim5-1414-60
    Splenectomy1-567-56
    Vinblastine7-147-42
    Vincristine7-147-42
    • * Adapted from the International Working Group.7