Diagnosis and management of immune thrombocytopenic purpura (ITP) remain largely dependent on clinical expertise and observations more than on evidence derived from clinical trials of high scientific quality. One major obstacle to the implementation of such studies and in producing reliable meta-analyses of existing data is a lack of consensus on standardized critical definitions, outcome criteria, and terminology. Moreover, the demand for comparative clinical trials has dramatically increased since the introduction of new classes of therapeutic agents, such as thrombopoietin receptor agonists, and innovative treatment modalities, such as anti-CD 20 antibodies. To overcome the present heterogeneity, an International Working Group of recognized expert clinicians convened a 2-day structured meeting (the Vicenza Consensus Conference) to define standard terminology and definitions for primary ITP and its different phases and criteria for the grading of severity, and clinically meaningful outcomes and response.These consensus criteria and definitions could be used by investigational clinical trials or cohort studies. Adoption of these recommendations would serve to improve communication among investigators, to enhance comparability among clinical trials, to facilitate meta-analyses and development of therapeutic guidelines, and to provide a standardized framework for regulatory agencies. (Blood.

IntroductionPrimary immune thrombocytopenia (ITP) is an acquired immunemediated disorder characterized by isolated thrombocytopenia, defined as a peripheral blood platelet count less than 100 ϫ 10 9 /L, and the absence of any obvious initiating and/or underlying cause of the thrombocytopenia. 1 Until recently, the abbreviation ITP stood for idiopathic thrombocytopenic purpura, but current awareness relating to the immune-mediated nature of the disease, and the absence or minimal signs of bleeding in a large proportion of cases have led to a revision of the terminology. 1 Concepts surrounding the mechanisms of thrombocytopenia in ITP have shifted from the traditional view of increased platelet destruction mediated by autoantibodies to more complex mechanisms in which both impaired platelet production and T cell-mediated effects play a role. [2][3][4][5][6] Recent epidemiologic data suggest that the incidence in adults is approximately equal for the sexes except in the mid-adult years (30-60 years), when the disease is more prevalent in women. 7,8 ITP is classified by duration into newly diagnosed, persistent (3-12 months' duration) and chronic (Ն 12 months' duration). 1 Whereas ITP in adults typically has an insidious onset with no preceding viral or other illness and it normally follows a chronic course, 9 ITP in children is usually short-lived with at least two-thirds recovering spontaneously within 6 months. 10 Signs and symptoms vary widely. Many patients have either no symptoms or minimal bruising, whereas others experience serious bleeding, which may include gastrointestinal hemorrhage (GI), extensive skin and mucosal hemorrhage, or intracranial hemorrhage (ICH). The severity of thrombocytopenia correlates to some extent but not completely with the bleeding risk. 7,11 Additional factors (eg, age, lifestyle factors, uremia) affect the risk and should be evaluated before the appropriate management is determined.The investigation and management of ITP patients vary widely. The purpose of this consensus document is to comment on new data and provide recommendations relating to diagnosis and treatment. Final judgment regarding care of individual patients should, however, lie with the responsible health care professional and be based on careful investigation of individual circumstances. MethodsComposition of the panel. The panel included 22 members with recognized clinical and research expertise in ITP representing North America (United States, 7; Canada, 1), Europe (France, 1; Italy, 2; Spain, 1; Switzerland, 1; United Kingdom, 8), and Australia (1).Assessment of the literature. Articles were identified by a computer-assisted search of the literature published in English using the National Library of Medicine PubMed database. The For personal use only. on May 7, 2018. by guest www.bloodjournal.org From search criteria were: 'immune thrombocytopenic purpura', 'idiopathic thrombocytopenic purpura', 'ITP', and 'autoimmune thrombocytopenic purpura'. A subsequent search was performed using the corresponding MedLin...

The role of rituximab, a chimeric monoclonal antibody directed against the CD20 antigen, in the treatment of patients with chronic idiopathic thrombocytopenic purpura (ITP) has not been determined. The effectiveness and side effects of this therapeutic modality were investigated in a cohort of 25 individuals with chronic ITP. All patients had ITP that had been resistant to between 2 and 5 different therapeutic regimens, including 8 patients who had already failed splenectomy. Patients were scheduled to receive intravenous rituximab at the dose of 375 mg/m 2 once weekly for 4 weeks. Rituximab infusion-related side effects were observed in 18 patients, but were of modest intensity and did not require discontinuation of treatment. A complete response (platelet count greater than 100 ؋ 10 9 /L) was observed in 5 cases, a partial response (platelet count between 50 and 100 ؋ 10 9 /L) in 5 cases, and a minor response (platelet count below 50 ؋ 10 9 /L, with no need for continued treatment) in 3 cases, with an overall response rate of 52%. In 7 cases, responses were sustained (6 months or longer). In 2 patients with relapsed disease, repeat challenge with rituximab induced a new response. In patients with a complete or partial response, a significant rise in platelet concentrations was observed early during the course of treatment, usually 1 week after the first rituximab infusion. No clinical or laboratory parameter was found to predict treatment outcome, although there was a suggestion that women and younger patients have a better chance of response. In conclusion, rituximab therapy has a limited but valuable effect in patients with chronic ITP. In view of its mild toxicity and the lack of effective alternative treatments, its use in the setting of chronic refractory ITP is warranted. (Blood. 2001; 98:952-957)