From bloodjournal.hematologylibrary.org by guest on May 16, 2013. For personal use only. 2011 117: 4190-4207 Prepublished online February 16, 2011; doi:10.1182/blood-2010-08-302984 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. 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Copyright 2011 by The American Society of Hematology; all rights reserved. From bloodjournal.hematologylibrary.org by guest on May 16, 2013. For personal use only. Review article The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia *Cindy Neunert,1 *Wendy Lim,2 Mark Crowther,3 Alan Cohen,4 Lawrence Solberg Jr,5 and Mark A. Crowther2 1University of Texas, Southwestern Medical Center, Dallas, TX; 2McMaster University, Hamilton, ON; 3Worcestershire Royal Hospital, Worcester, United Kingdom; 4Children’s Hospital of Philadelphia, Philadelphia, PA; and 5Mayo Clinic, Jacksonville, FL Immune thrombocytopenia (ITP) is com- of the available evidence. We have en- expert opinion in these clinical areas. Our monly encountered in clinical practice. In deavored to identify, abstract, and pres- review identified the need for additional 1996 the American Society of Hematology ent all available methodologically rigor- studies in many key areas of the therapy published a landmark guidance paper de- ous data informing the treatment of ITP. of ITP such as comparative studies of signed to assist clinicians in the manage- We provide evidence-based treatment rec- “front-line” therapy for ITP, the manage- ment of this disorder. Since 1996 there ommendations using the GRADE system ment of serious bleeding in patients with have been numerous advances in the in those areas in which such evidence ITP, and studies that will provide guid- management of both adult and pediatric exists. We do not provide evidence in ance about which therapy should be used ITP. These changes mandated an update those areas in which evidence is lacking, as salvage therapy for patients after fail- in the guidelines. This guideline uses a or is of lower quality—interested readers ure of a first-line intervention. (Blood. rigorous, evidence-based approach to the are referred to a number of recent, 2011;117(16):4190-4207) location, interpretation, and presentation consensus-based recommendations for Introduction Immune thrombocytopenia (ITP) is characterized by isolated (including the use of antiplatelet agents) are safe. We encourage thrombocytopenia often occurring in the absence of identifiable publication of observational data and clinical trials to provide and specific precipitants. In 1996 the American Society of Hematol- evidence to guide therapy in these areas. A condensed summary of ogy (ASH) published a comprehensive guideline on this disorder,1 recommendations is provided in Table 1. which has become the reference standard for the diagnosis and treatment of the disease. However, given important recent advances in both the definition and treatment of ITP, an update of the guideline is required. This document summarizes the literature Nomenclature and diagnosis describing the diagnosis and management of ITP focusing on changes since the publication of the initial guideline in 1996. In this The disease and its most widely accepted abbreviation, ITP, has guideline we have performed comprehensive literature reviews and variably been defined as “immune thrombocytopenic purpura,” have presented the evidence using the GRADE system, which “idiopathic thrombocytopenic purpura,” and, most recently, “im- categorizes evidence based on the quality of the contributing mune thrombocytopenia.”5 It is an autoimmune disorder character- evidence and the strength that the evidence brings to the recommen- ized by immunologic destruction of otherwise normal platelets dations.2 We have attempted to keep our literature review and most commonly occurring in response to an unknown stimulus. ITP recommendations practical and concise and have limited our may occur in isolation (primary) or in association with other disorders recommendations to those areas with sufficient evidence. In other (secondary). Secondary causes include autoimmune diseases (particu- areas we do not provide recommendations; readers requiring a larly the antiphospholipid antibody syndrome), viral infections (includ- more in-depth review are referred to recent consensus-based ing hepatitis C [HCV] and human immunodeficiency virus [HIV]), guidelines, which does present recommendations in areas where and certain drugs (Table 2). Historically, ITP was believed to be strong evidence is lacking.3,4 We provide recommendations for caused by increased platelet destruction at a rate that exceeded patients with both primary and selected secondary forms of ITP. We production by a compensating bone marrow. New knowledge do not provide recommendations for neonatal ITP. Overall, we has questioned this model, providing evidence that platelet have noted a lack of good-quality evidence in many areas of production is also decreased in many patients with ITP.6 concern for physicians involved in the day-to-day management of An International Working Group (IWG) consensus panel of patients with ITP. These areas include the management of bleeding both adult and pediatric experts in ITP recently provided guidance in patients with ITP, evidence to guide second-line therapies in on terminology, definitions, and outcome criteria for this disorder.7 children and adults, evidence to guide the timing of splenectomy, Primary ITP was defined by the IWG as a platelet count less than and evidence to support platelet thresholds at which interventions 100 ϫ 109/L in the absence of other causes or disorders that may be Submitted August 20, 2010; accepted January 18, 2011. Prepublished online The online version of this article contains a data supplement. as Blood First Edition paper, February 16, 2011; DOI: 10.1182/blood-2010-08- 302984. *C.N. and W.L. contributed equally to this work. © 2011 by The American Society of Hematology 4190 BLOOD, 21 APRIL 2011 ⅐ VOLUME 117, NUMBER 16 From bloodjournal.hematologylibrary.org by guest on May 16, 2013. For personal use only. BLOOD, 21 APRIL 2011 ⅐ VOLUME 117, NUMBER 16 ASH 2011 EVIDENCE-BASED PRACTICE GUIDELINE FOR ITP 4191 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