Immune thrombocytopenia (ITP) is commonly encountered in clinical practice. In 1996 the American Society of Hematology published a landmark guidance paper designed to assist clinicians in the management of this disorder. Since 1996 there have been numerous advances in the management of both adult and pediatric ITP. These changes mandated an update in the guidelines. This guideline uses a rigorous, evidence-based approach to the location, interpretation, and presentation of the available evidence. We have endeavored to identify, abstract, and present all available methodologically rigorous data informing the treatment of ITP. We provide evidence-based treatment recommendations using the GRADE system in those areas in which such evidence exists. We do not provide evidence in those areas in which evidence is lacking, or is of lower quality-interested readers are referred to a number of recent, consensus-based recommendations for expert opinion in these clinical areas. Our review identified the need for additional studies in many key areas of the therapy of ITP such as comparative studies of "front-line" therapy for ITP, the management of serious bleeding in patients with ITP, and studies that will provide guidance about which therapy should be used as salvage therapy for patients after failure of a first-line intervention. (Blood. 2011;117(16):4190-4207)

Background: Despite an increase in the number of therapies available to treat patients with immune thrombocytopenia (ITP), there are minimal data from randomized trials to assist physicians with the management of patients. Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about the management of ITP. Methods: In 2015, ASH formed a multidisciplinary guideline panel that included 8 adult clinical experts, 5 pediatric clinical experts, 2 methodologists with expertise in ITP, and 2 patient representatives. The panel was balanced to minimize potential bias from conflicts of interest. The panel reviewed the ASH 2011 guideline recommendations and prioritized questions. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including evidence-to-decision frameworks, to appraise evidence (up to May 2017) and formulate recommendations. Results: The panel agreed on 21 recommendations covering management of ITP in adults and children with newly diagnosed, persistent, and chronic disease refractory to first-line therapy who have non–life-threatening bleeding. Management approaches included: observation, corticosteroids, IV immunoglobulin, anti-D immunoglobulin, rituximab, splenectomy, and thrombopoietin receptor agonists. Conclusions: There was a lack of evidence to support strong recommendations for various management approaches. In general, strategies that avoided medication side effects were favored. A large focus was placed on shared decision-making, especially with regard to second-line therapy. Future research should apply standard corticosteroid-dosing regimens, report patient-reported outcomes, and include cost-analysis evaluations.

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Summary. Background: The burden of severe bleeding in adults and children with immune thrombocytopenia (ITP) has not been established. Objectives: To describe the frequency and severity of bleeding events in patients with ITP, and the methods used to measure bleeding in ITP studies. Patients/Methods: We performed a systematic review of all prospective ITP studies that enrolled 20 or more patients. Two reviewers searched Medline, Embase, CINAHL and the Cochrane registry up to May 2014. Overall weighted proportions were estimated using a random effects model. Measurement properties of bleeding assessment tools were evaluated. Results: We identified 118 studies that reported bleeding (n = 10 908 patients). Weighted proportions for intracerebral hemorrhage (ICH) were 1.4% for adults (95% confidence interval [CI], 0.9-2.1%) and 0.4% for children (95% CI, 0.2-0.7%; P < 0.01), most of whom had chronic ITP. The weighted proportion for severe (non-ICH) bleeding was 9.6% for adults (95% CI, 4.1-17.1%) and 20.2% for children (95% CI, 10.0-32.9%; P < 0.01) with newly-diagnosed or chronic ITP. Methods of reporting and definitions of severe bleeding were highly variable in primary studies. Two bleeding assessment tools (Buchanan 2002 for children; Page 2007 for adults) demonstrated adequate interrater reliability and validity in independent assessments. Conclusions: ICH was more common in adults and tended to occur during chronic ITP; other severe bleeds were more common in children and occurred at all stages of disease. Reporting of non-ICH bleeding was variable across studies. Further attention to ITP-specific bleeding measurement in clinical trials is needed to improve standardization of this important outcome for patients.

Controversy exists regarding management of children newly diagnosed with immune thrombocytopenic purpura (ITP

This article summarizes our approach to the management of children and adults with primary immune thrombocytopenia (ITP) who do not respond to, cannot tolerate, or are unwilling to undergo splenectomy. We begin with a critical reassessment of the diagnosis and a deliberate attempt to exclude nonautoimmune causes of thrombocytopenia and secondary ITP. For patients in whom the diagnosis is affirmed, we consider observation without treatment.Observation is appropriate for most asymptomatic patients with a platelet count of 20 to 30 3 10 9 /L or higher. We use a tiered approach to treat patients who require therapy to increase the platelet count. Tier 1 options (rituximab, thrombopoietin receptor agonists, low-dose corticosteroids) have a relatively favorable therapeutic index. We exhaust all Tier 1 options before proceeding to Tier 2, which comprises a host of immunosuppressive agents with relatively lower response rates and/or greater toxicity. We often prescribe Tier 2 drugs not alone but in combination with a Tier 1 or a second Tier 2 drug with a different mechanism of action. We reserve Tier 3 strategies, which are of uncertain benefit and/or high toxicity with little supporting evidence, for the rare patient with serious bleeding who does not respond to Tier 1 and Tier 2 therapies. (Blood. 2016;128(12): 1547-1554 Case 1A 10-year-old male was diagnosed with primary immune thrombocytopenia (ITP) 5 months ago when he presented with epistaxis, petechiae, bruising, and a platelet count of 5 3 10 9 /L. He responded transiently to intravenous immunoglobulin G (IgG), but epistaxis recurred 2 weeks later. He subsequently received a short course of oral corticosteroids to which he had a temporary response in platelet count and cessation of epistaxis. Since discontinuing corticosteroids, he has had only occasional bruising and petechiae. His platelet count is currently 13 3 10 9 /L. He states that ITP is not interfering with activities.

Objectives: The disease caused by severe acute respiratory syndrome coronavirus 2, known as coronavirus disease 2019, has resulted in a global pandemic. Reports are emerging of a new severe hyperinflammatory syndrome related to coronavirus disease 2019 in children and adolescents. The Centers for Disease Control and Prevention has designated this disease multisystem inflammatory syndrome in children. Our objective was to develop a clinical inpatient protocol for the evaluation, management, and follow-up of patients with this syndrome. Data Sources: The protocol was developed by a multidisciplinary team based on relevant literature related to coronavirus disease 2019, multisystem inflammatory syndrome in children, and related inflammatory syndromes, as well as our experience caring for children with multisystem inflammatory syndrome in children. Data were obtained on patients with multisystem inflammatory syndrome in children at our institution from the pre-protocol and post-protocol periods. Data Synthesis: Our protocol was developed in order to identify cases of multisystem inflammatory syndrome in children with high sensitivity, stratify risk to guide treatment, recognize co-infectious or co-inflammatory processes, mitigate coronary artery abnormalities, and manage hyperinflammatory shock. Key elements of evaluation include case identification using broad clinical characteristics and comprehensive laboratory and imaging investigations. Treatment centers around glucocorticoids and IV immunoglobulin with biologic immunomodulators as adjuncts. Multidisciplinary follow-up after discharge is indicated to manage continued outpatient therapy and evaluate for disease sequelae. In nearly 2 months, we admitted 54 patients with multisystem inflammatory syndrome in children, all of whom survived without the need for invasive ventilatory or mechanical circulatory support. After institution of this protocol, patients received earlier treatment and had shorter lengths of hospital stay. Conclusions: This report provides guidance to clinicians on evaluation, management, and follow-up of patients with a novel hyperinflammatory syndrome related to coronavirus disease 2019 known as multisystem inflammatory syndrome in children. It is based on the relevant literature and our experience. Instituting such a protocol during a global pandemic is feasible and is associated with patients receiving treatment and returning home more quickly.

Key Points• Severe thrombocytopenia is rare and major hemorrhage is uncommon in children with persistent and chronic ITP.• In children with persistent or chronic ITP, there is a trend toward reserving drug therapy for those experiencing significant bleeding. /L was uncommon (7%, 7%, and 4%, respectively). Remission occurred in 37% of patients between 28 days and 6 months, 16% between 6 and 12 months, and 24% between 12 and 24 months. There were no reports of intracranial hemorrhage, and the most common site of bleeding was skin. In patients with severe thrombocytopenia we observed a trend toward more drug treatment with increasing number of bleeding sites. Our data support that ITP is a benign condition for most affected children and that major hemorrhage, even with prolonged severe thrombocytopenia, is rare. (Blood. 2013;121(22):4457-4462)