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...

Summary.  von Willebrand disease (VWD) is a bleeding disorder caused by inherited defects in the concentration, structure, or function of von Willebrand factor (VWF). VWD is classified into three primary categories. Type 1 includes partial quantitative deficiency, type 2 includes qualitative defects, and type 3 includes virtually complete deficiency of VWF. VWD type 2 is divided into four secondary categories. Type 2A includes variants with decreased platelet adhesion caused by selective deficiency of high‐molecular‐weight VWF multimers. Type 2B includes variants with increased affinity for platelet glycoprotein Ib. Type 2M includes variants with markedly defective platelet adhesion despite a relatively normal size distribution of VWF multimers. Type 2N includes variants with markedly decreased affinity for factor VIII. These six categories of VWD correlate with important clinical features and therapeutic requirements. Some VWF gene mutations, alone or in combination, have complex effects and give rise to mixed VWD phenotypes. Certain VWD types, especially type 1 and type 2A, encompass several pathophysiologic mechanisms that sometimes can be distinguished by appropriate laboratory studies. The clinical significance of this heterogeneity is under investigation, which may support further subdivision of VWD type 1 or type 2A in the future.

Over the last decade, there have been numerous developments and changes in treatment practices for the management of patients with immune thrombocytopenia (ITP). This article is an update of the International Consensus Report published in 2010. A critical review was performed to identify all relevant articles published between 2009 and 2018. An expert panel screened, reviewed, and graded the studies and formulated the updated consensus recommendations based on the new data. The final document provides consensus recommendations on the diagnosis and management of ITP in adults, during pregnancy, and in children, as well as quality-of-life considerations.

Under the auspices of an International Working Group, seven centers submitted diagnostic and follow-up information on 1545 patients with World Health Organization-defined polycythemia vera (PV). At diagnosis, median age was 61 years (51% females); thrombocytosis and venous thrombosis were more frequent in women and arterial thrombosis and abnormal karyotype in men. Considering patients from the center with the most mature follow-up information (n=337 with 44% of patients followed to death), median survival (14.1 years) was significantly worse than that of the age- and sex-matched US population (P<0.001). In multivariable analysis, survival for the entire study cohort (n=1545) was adversely affected by older age, leukocytosis, venous thrombosis and abnormal karyotype; a prognostic model that included the first three parameters delineated risk groups with median survivals of 10.9–27.8 years (hazard ratio (HR), 10.7; 95% confidence interval (CI): 7.7–15.0). Pruritus was identified as a favorable risk factor for survival. Cumulative hazard of leukemic transformation, with death as a competing risk, was 2.3% at 10 years and 5.5% at 15 years; risk factors included older age, abnormal karyotype and leukocytes ⩾15 × 109/l. Leukemic transformation was associated with treatment exposure to pipobroman or P32/chlorambucil. We found no association between leukemic transformation and hydroxyurea or busulfan use.