American Society Of Hematology Guidelines Research Articles

Potential Overuse of Primary Thromboprophylaxis in Medical Inpatients at Low Risk of Venous Thromboembolism

Background: Venous thromboembolism (VTE) is a common cause of morbidity and mortality in the United States. Annually, up to 1 in 120 people develop VTE, approximating the incidence of stroke. Given that hospitalization and acute medical illness increase the risk of VTE, hospital-associated VTE represents a preventable cause of morbidity and mortality. Accordingly, accreditation and regulatory agencies endorse inpatient pharmacologic VTE prophylaxis (PPX) as a quality measure. In order to raise rates of PPX prescribing, many health systems have adopted a default approach to electronic ordering, in which clinicians must "opt-out" of PPX prescription. However, this strategy may cause medical overuse and avoidable harms, which has prompted the American Society of Hematology (ASH) to recommend a risk-adapted approach to PPX. One risk model endorsed by ASH is the IMPROVE-VTE risk assessment model, which can identify patients who are at low risk for VTE and therefore may not warrant pharmacologic PPX. We therefore sought to compare the actual practice of PPX prescribing to the guideline-recommended strategy according the IMPROVE-VTE model in a large, contemporary population of medical inpatients. Methods: In this observational study, we used electronic health record data to identify adult, medical inpatients hospitalized on general medical and subspecialty services at Yale-New Haven Hospital from 1/1/14-12/31/18. We excluded patients who were pregnant, admitted for VTE, taking full dose anticoagulation on admission, admitted for bleeding, or had a platelet count of < 50,000/µL. For each patient, we calculated the IMPROVE-VTE score using the previously validated model weights: 3 points for a prior history of VTE; 2 points for known thrombophilia, lower limb paralysis, or active cancer; 1 point for immobilization, admission to the intensive care unit, or age ≥ 60 years. For each component other than age, we used ICD-9 and ICD-10 codes that were billed either prior to or upon admission to determine the presence of these risk factors. In order to simulate the decision to initiate PPX on hospital admission, we calculated each patient's IMPROVE-VTE score at the time of admission. In accordance with the ASH guidelines, we used an IMPROVE-VTE score of <2 to differentiate patients at low-risk of hospital-associated VTE from those at high-risk. We used inpatient medication order history data to determine receipt of pharmacologic PPX. We used χ2 testing to compare the relative frequency of PPX prescribing on admission between patients at low-risk and high-risk for VTE. Results: We identified 135,288 medical inpatients during the study period, of whom 99,380 met inclusion criteria. The average age was 63.5 years-old (standard deviation 18 years); 51% of patients were female; 68% of patients were white. Of all the included patients, 81% received pharmacologic prophylaxis; of these patients, 78% received unfractionated heparin subcutaneously and 22% received low molecular weight heparin subcutaneously. Among all hospitalized patients, 78% had an IMPROVE-VTE score of <2 (32% had a score of 0 and 46% had a score of 1). Among these patients at low risk of hospital-associated VTE, 81% received pharmacologic PPX. Differences in prophylaxis rates between patients at low vs high risk of VTE were statistically significant (p<0.001). Conclusion: In this contemporary cohort of adult, medical inpatients, >80% of patients who were at low risk of hospital-associated VTE received pharmacologic PPX, representing a group in whom PPX may be unnecessary. Using a risk-adapted approach such as the IMPROVE-VTE risk assessment model, rather than default PPX ordering, may reduce medical overuse and avoidable harms. Disclosures Chaudhry: CVS State of CT Clinical Pharmacy Program: Other: Paid Reviewer for CVS State of CT Clinical Pharmacy Program.

Positivity Rate of Systematic Bone Marrow Smear Above 60-Year-Old Patients with Newly Diagnosed Immune Thrombocytopenia to Screen for Associated Hematological Malignancy. Results from the French Prospective Multicenter Carmen Registry

Introduction:There are discrepancies across recommendations about the indication of bone marrow smear in adults diagnosed for immune thrombocytopenia (ITP). The 2011 American Society of Hematology guidelines do not recommend bone marrow smear in case of typical ITP. In contrast, the 2010 international consensus and the 2017 French guidelines recommend systematic bone marrow smear in adults aged >60 years even in case of typical ITP to detect a blood cancer, particularly myelodysplastic syndrome. This recommendation is driven from expert consensus. Data are lacking about the positivity rate of this examination in older patients with typical ITP. The aim of this study was to assess the positivity rate of bone marrow smear at ITP diagnosis in >60-year-old patients with no other clinical or biological sign of hematological malignancy. Methods:Data source was theCARMEN (Cytopénies Auto-immunes : Registre Midi-PyréneEN) registry. All adult patients with an incident diagnosis of ITP in the French Midi-Pyrénées region (South of France, 3 million inhabitants) are prospectively enrolled since June 2013 in the multicenter CARMEN registry. ITP is defined by international guidelines (platelet count <100 x 109/L and exclusion of other causes of thrombocytopenia). Investigations performed at ITP diagnosis in a real-life basis, including bone marrow smear, are recorded with their results. Study population was selected among the patients included in the CARMEN registry from June 2013 to December 2018. Inclusion criteria were: age>60 years; absence of clinical signs of hematological malignancy (lymphadenopathy, hepatomegaly, splenomegaly); isolated thrombocytopenia on blood count; bone marrow smear performed at ITP diagnosis. We described patients with abnormal bone marrow smear and implications for ITP management. Results:We identified 114patients (66 men and 48 women) satisfying all inclusion criteria. Mean age at ITP diagnosis was 76 years (standard deviation - SD: 9 years). Platelet count at diagnosis was 32.7 x 109/L (SD: 27.7 x 109/L) and 58 patients presented with bleeding: skin bleeding only (n=33), oral bleeding (n=17), epistaxis (n=10) and hematuria (n=3). Only one patient had an abnormal bone marrow smear corresponding to a characterized hematological disease: a myelodysplastic syndrome. It was a 62-year-old man without medical history who presented in 2014 with extensive skin bleeding, and isolated thrombocytopenia (6 x 109/L). Other blood count parameters were: hemoglobin: 15.2 g/dL; MCV: 83 fL; leukocytes: 5.3 x 109/L; polynuclear neutrophils: 3.5 x 109/L; lymphocytes: 1.0 x 109/L; monocytes: 0,3 x 109/L . Bone marrow smear revealed normal cellularity. The megakaryocytic lineage was normally represented with significant number of megakaryocytes with multiple separated nuclei. Significant dysgranulopoiesis was also observed with pseudo-Pelger-Huët anomaly and cytoplasmic hypogranulation. Some erythroblasts with defective haemoglobination or cytoplasmic vacuolation were present. This aspect was compatible with the diagnosis of myelodysplastic syndrome with multilineage dysplasia (MDS-MLD). Karyotype was normal. The patient was initially treated for ITP with steroids and intravenous immunoglobulins (with partial response), then with danazol (complete response), eltrombopag (after loss of response to danazol and ocular bleeding, resulting in complete response) and more recently romiplostim (after loss of response to eltrombopag, resulting in complete response). He was treated in 2019 by rituximab to spare exposure to thrombopoietin receptor agonists, without efficacy. Before Rituximab, another bone marrow smear was performed (4 years after the first one) with the same cytologic and cytogenetic features (MLD-MDS with normal caryotype). Conclusions:Diagnosis of hematological malignancy is very uncommon in >60 year-old patients who present with typical ITP. Myelodysplastic syndrome was found in 1 (0.8%) patient in this series, and did not impact the management or the evolution of the patient with a five-year follow-up. Overall, this study sustains guidelines that does not recommend systematic testing for bone marrow examination in >60 year-old patients with typical ITP. Disclosures Comont: BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees. Recher:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sunesis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Honoraria; Macrogenics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Beyne-Rauzy:Novartis: Research Funding; Cellgene: Research Funding. Moulis:CSL Behring: Research Funding; Amgen pharma: Research Funding, Speakers Bureau; Novartis pharma: Research Funding, Speakers Bureau.

Assessment of Provider Practices Regarding Management of VTE in Pediatric Leukemia

The development of venous thromboembolism (VTE) is a known complication occurring in children with leukemia with a reported incidence ranging from 1 to 37% (Ghanem, et al, Pediatric Blood & Cancer, 2017) and can be a source of significant morbidity. Known risk factors for VTE include central venous catheter (CVC) use, thrombophilia, and certain medications, such as asparaginase (Caruso, et al, Blood, 2006.) Despite the known occurrence of VTE in this population, there are no leukemia-specific guidelines for VTE management. Anticoagulant use in children with frequent periods of thrombocytopenia and coagulopathy is not risk free. Various elements of management lack standardization and consensus among practitioners. Given that the majority of pediatric leukemia patients are treated according to standardized protocols, it may be beneficial to standardize anticoagulation care guidelines. Therefore, the primary objective of this study was to assess current practices regarding the management of VTE in the pediatric leukemia population. We performed a cross sectional, anonymous, electronic survey of members of the American Society of Hematology (ASH) who self-identified as focusing in pediatric hematology or pediatric hematology/oncology, and the pediatric subcommittee of VENUS (VTE Network of the Hemostasis and Thrombosis Research Society) using Qualtrics, a secure online survey tool. Survey items included questions on demographics and clinical practice. Respondents were excluded if they were not board certified/eligible, if they did not participate in patient care, or if they did not answer survey research questions. A $25 gift card incentive was offered anonymously. This study was approved by both the Weill Cornell Medicine and Northwell Health IRBs. Of 870 surveys distributed, 154 were submitted, giving a 17.7% response rate. Twelve surveys were excluded, leaving 142 surveys for final analysis. There was even distribution of years in practice and size of clinical program among respondents (Figure 1A). Most respondents identified as being in hematology or combined practice. 50% of responding physicians (n=136) reported treating CVC-associated VTE for 3 months. 92% of respondents (n=138) report repeating imaging of the VTE with 58% (n=124) repeating at 6 weeks, and 31% at 3 months. 40% of respondents (n=131) treat cerebral venous sinus thrombosis (CVST) for 3 months, followed by 24% treating for 6 months. 95% of respondents (n=131) repeat imaging for CVST and of these individuals, 40% repeat imaging at 6 weeks followed by 50% at 3 months. The most frequently utilized anticoagulant class was heparins (n=140); respondents also reported using the direct Xa inhibitors Rivaroxaban (21%) and Apixaban (14%). Within the group utilizing direct Xa inhibitors, those in practice the longest (≥16 years) had the highest percentage of use (Figure 1B.) When asked at what platelet counts they hold therapeutic anticoagulation (n=140), 39% of respondents chose 50 x 109/L, 33% chose 30 x 109/L, and 16% chose 20 x 109/L. One person chose 100, x 109/L, 11% said they did not hold anticoagulation for thrombocytopenia, and 2 respondents gave platelet transfusions rather than hold anticoagulation (one at a cutoff below 30 x 109/L and one below 50 x 109/L). While no significant associations were seen, the highest percentage among individual groups using a platelet cutoff of less than 50 x 109/L were among those in practice longest, and those in the largest centers (Figure 1C). The results of this survey revealed variation in practice among practitioners regarding VTE management and prevention. Despite the lack of data in this population, a number of physicians are using direct Xa inhibitors in children with leukemia for anticoagulation. Imaging is being done earlier than treatment is being discontinued, potentially implying it is being used to monitor for progression, rather than help guide duration of therapy. Our survey had some limitations, including the low response rate and missing data for questions, which may be due to electronic data collection errors or respondent choice. Recent ASH guidelines endorsed by the Children's Oncology Group propose limited general guidelines and do not consider a cancer patient's unique VTE risk profile. Given the variation seen, multi-center, prospective clinical trials are urgently needed for developing consensus guidelines for the management of VTE in children with leukemia. Figure 1 Disclosures Cooley: off-label: Other: drug use. Acharya:Takeda: Membership on an entity's Board of Directors or advisory committees; BioProducts Laboratory: Membership on an entity's Board of Directors or advisory committees; Bayer Pharmaceuticals, LLC: Research Funding; Novonordisk: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Anticoagulations that will be discussed are off-label in children.

NewsCAP: American Society of Hematology guidelines issued for VTE.

NewsCAP: American Society of Hematology guidelines issued for VTE.

Interactive Summary of Findings tables: the way to present and understand results of systematic reviews.

The JBI Database of Systematic Reviews and Implementation Reports continues to enhance its systematic reviews by including GRADE (Grading of Recommendations Assessment, Development and Evaluation) Summary of Findings (SoF) tables. Summary of Findings tables are concise, tabular summaries of the evidence that address a specific health-related question.1 They include information about the main outcomes, the type and number of studies, the relative and absolute estimates of the effect or association, important comments and a plain language summary to aid interpretation and a rating of the certainty of evidence (also known as quality of the evidence).1 Several randomized trials have shown that well designed SoF tables improve understanding and retrieval of information from a systematic review2-4 and they are a standard feature of Cochrane and are often used in other reviews.5-7 However, in the GRADE Working Group's DECIDE project (www.decide-collaboration.eu)8 and during guideline development work, it became apparent that a “flexible standardization” of presenting information in SoF tables is required to further enhance understanding and uptake of information. These observations led to the development of electronic interactive versions of SoF tables (iSoFs) that allow presenting the same underlying information in several formats that vary in content and graphical layout. These electronic versions are available on dedicated websites and, from this issue of the journal, are linked directly from the standard SoF and text of a Joanna Briggs Institute (JBI) systematic review. An example is available in Vincze et al.9 evaluating the use of nutrition for gestational and postpartum weight management in this issue of the journal. Low certainty evidence from 23 studies in 5230 patients compiled in the review suggests that nutritional interventions may reduce gestational weight gain, a continuous outcome described in this iSoF: https://bit.ly/2Ofg9Av, by 1.25 (95% confidence interval: 0.4 to 2.1) kg compared with other interventions. Authors of JBI systematic reviews will use the GRADE Working Group's official tool, GRADEpro (McMaster University/EvidencePrime, Inc., Hamilton, ON, Canada), to create these iSoF tables. The integrated GRADE Handbook provides guidance for how to create iSoFs, how to embed them in other documents, such as systematic reviews, Health Technology Assessment reports and healthcare guidelines where they can function as decision support tools and aids. Detailed guidance for how to produce SoF tables is also available in GRADE research articles that describe good practices and the process for creating accurate SoF tables for interventions and diagnostic test accuracy reviews.4,10-14 Examples of the use of iSoFs include recent European Commission Breast Cancer guidelines and American Society of Hematology guidelines where recommendations are supported by an iSoF.15-18 We are delighted that the JBI has taken this innovative step to include iSoF tables in their reviews. These steps will make for better evidence integration in decision tools and sharing globally.

Structured decision-making drives guidelines panels' recommendations “for” but not “against” health interventions

Background and ObjectivesThe determinants of guideline panels’ recommendations remain uncertain. The objective of this study was to investigate factors considered by members of 8 panels convened by the American Society of Hematology (ASH) to develop guidelines using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Study Design and SettingWeb-based survey of the participants in the ASH guidelines panels. Analysis: two-level hierarchical, random-effect, multivariable regression analysis to explore the relation between GRADE and non-GRADE factors and strength of recommendations (SOR). ResultsIn the primary analysis, certainty in evidence [OR = 1.83; (95CI% 1.45–2.31)], balance of benefits and harms [OR = 1.49 (95CI% 1.30–1.69)] and variability in patients’ values and preferences [OR = 1.47 (95CI% 1.15–1.88)] proved the strongest predictors of SOR. In a secondary analysis, certainty of evidence was associated with a strong recommendation [OR = 3.60 (95% CI 2.16–6.00)] when panel members recommended “for” interventions but not when they made recommendations “against” interventions [OR = 0.98 (95%CI: 0.57–1.8)] consistent with “yes” bias. Agreement between individual members and the group in rating SOR varied (kappa ranged from −0.01 to 0.64). ConclusionGRADE's conceptual framework proved, in general, to be highly associated with SOR. Failure of certainty of evidence to be associated with SOR against an intervention, suggest the need for improvements in the process.

Initial Diagnostic Work-Up of Acute Leukemia: ASCO Clinical Practice Guideline Endorsement of the College of American Pathologists and American Society of Hematology Guideline.

The College of American Pathologists (CAP) and the American Society of Hematology (ASH) developed an evidence-based guideline on the initial diagnostic work-up of acute leukemia (AL). Because of the relevance of this topic to the ASCO membership, ASCO reviewed the guideline and applied a set of procedures and policies for endorsing clinical practice guidelines that have been developed by other professional organizations. The CAP-ASH guideline on initial diagnostic work-up of AL was reviewed for developmental rigor by methodologists. Then, an ASCO Endorsement Expert Panel updated the literature search and reviewed the content and recommendations. The ASCO Expert Panel determined that the recommendations from the guideline, published in 2016, are clear, thorough, and based on the most relevant scientific evidence. ASCO fully endorsed the CAP-ASH guideline on initial diagnostic work-up of AL and included some discussion points according to clinical practice and updated literature. Twenty-seven guideline statements were reviewed. Some discussion points were included to better assess CNS involvement in leukemia and to provide novel insights into molecular diagnosis and potential markers for risk stratification and target therapy. These discussions are categorized into four sections: (1) initial diagnosis focusing on basic diagnostics and determination of risk parameters, (2) molecular markers and minimal residual disease detection, (3) context of referral to another institution with expertise in the management of AL, and (4) reporting and record keeping for better outlining and follow-up discussion. Additional information is available at: www.asco.org/hematologic-malignancies-guidelines .

Evidence-based management of immune thrombocytopenia: ASH guideline update.

In 1996 and 2011, the American Society of Hematology (ASH) supported efforts to create guidelines for the diagnosis and management of patients with immune thrombocytopenia (ITP). These guidelines used different approaches to arrive at recommendations for testing and treatment. Despite differences in methodology, in both cases there was a paucity of randomized trials to inform recommendations. As data on the diagnosis and management of ITP expands, the ASH Committee on Quality is dedicated to maintaining updated guidelines representing recent evidence and guideline methodology. Here, we will review the updated ASH guidelines on ITP with a focus on recommendations with new understanding and future research to close knowledge gaps.

Antiplatelet Antibody Testing in Immune Thrombocytopenia and Evans Syndrome: Longitudinal Serologic Evolution and Relation to Clinical Features

Introduction: Antiplatelet antibody (APA) testing is considered an adjunct laboratory test in the diagnosis of immune thrombocytopenia (ITP). While it is not routinely obtained owing to inconsistent sensitivity and specificity in prior studies (Neunert et al, 2011), the definition of ITP used in these studies was not standardized. Additionally, potential clinical utility of this testing beyond diagnosis has been suggested, such as correlations between certain serologic patterns and response to IVIG (Peng et al, 2014). In consideration of these prior findings, we undertook a retrospective analysis of APA testing [glycoprotein-specific testing done by the commercial PakAuto assay (Immucor, Brookfield, WI), a monoclonal antibody immobilization of platelet antigens (MAIPA) assay, with all testing performed by the same laboratory] utilizing standardized ITP and Evans syndrome (ES) diagnostic criteria for patient inclusion. We examined serologic evolution over time and relation of antibody positivity to disease severity and response to therapies.Methods: Data collected for analysis included dates and results of APA testing (including disease status and platelet count at time of testing), patient demographics, and disease characteristics. Satisfaction of the 2011 American Society of Hematology (ASH) ITP diagnostic criteria were required for ITP patient inclusion and standard definitions of disease severity and response to treatment from the ASH guidelines were used in analysis. Logistic regression was used to model the probability of disease severity (non-severe, severe, or refractory) and treatment response (to corticosteroids or IVIG) based on serologic findings. Longitudinal serologic evolution in patients with multiple APA assays were analyzed.Results: A total of 214 APA assays from 115 ITP patients and 12 ES patients were collected; results from eluate testing (direct assay) only were used in analysis. Baseline patient characteristics are listed in Table 1. Of 7 possible positive test serologic patterns, only 4 were seen (Figure 1); antibodies against both GPIIb/IIIa and GPIb/IX were required for the presence of antibodies against GPIa/IIa. A multinomial logistic regression model including disease severity, age, sex, duration of disease, and platelet count at time of APA assay found a statistically significant predictive relationship between an increasing number of positive antibodies and disease severity [relative to non-severe ITP, relative risk ratio for severe ITP and refractory ITP was 1.89 (P=0.001) and 2.38 (P=0.004), respectively, per one additional positive antibody, Figure 2]. Multiple logistic regression models including antibody positivity to each platelet glycoprotein (GPIIb/IIIa, GPIb/IX, or GPIa/IIa), age, sex, disease duration and splenectomy status found a significant predictive relation between presence of anti-GPIa/IIa and non-response to corticosteroid treatment (odds ratio, 0.082, P=0.008). No significant relation was found between an antibody and non-response to IVIG. Fifty patients had multiple (2 to 5) APA assays performed over months to years. In evaluation of serologic evolution over time, all 7 patients who entered clinical remission also converted from a positive to a negative serology; 22 patients had stable serologic findings over time; 5 patients had a reduction in number of positive antibodies; and 18 patients demonstrated evidence for epitope spreading, with an increase in the number of positive antibodies (Figure 3). The sensitivity of a positive APA assay for the presence of active ITP was 91%. The sensitivity and specificity of a negative APA assay for remission in a patient with previously confirmed ITP (N=40 assays in patients with clinical remission in the study) were 88% and 91%, respectively.Conclusions: The MAIPA-based direct APA assay is sensitive for the presence of active ITP in patients satisfying 2011 ASH diagnostic criteria. To our knowledge, this is the first study demonstrating that a higher number of positive glycoprotein-specific antibodies may predict for more severe disease as defined by 2011 ASH disease severity criteria. Anti-GPIa/IIa antibodies only occur in the setting of pre-existing positivity for both anti-GPIIb/IIIa and anti-GPIb/IX antibodies, possibly due to a distinctive sequence of epitope spreading. Serologic testing typically turns negative when a patient enters clinical remission. [Display omitted] DisclosuresAl-Samkari:Agios: Consultancy. Kuter:Novartis: Consultancy; Pfizer: Consultancy; Syntimmune: Consultancy; Argenx: Consultancy; Dova Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; ONO: Consultancy; Amgen Inc.: Consultancy; Bioverativ: Consultancy, Research Funding; Principia: Research Funding; Rigel: Consultancy, Research Funding; BMS: Research Funding; Protalex: Research Funding.

How Do ASH Guidelines Panels Make Decisions? Association between Decision Making Factors and the Strength of Recommendations

Background: Clinical practice guidelines (CPGs) represent a key mechanism for optimizing health care decision making. CPGs are a product of discussion by a group of, typically, 10-20 individuals with varying expertise. Little is known how CPG panels actually make their recommendations.Objective: In a study of real-life decision making, we investigated the factors considered by members of panels convened by the American Society of Hematology (ASH) to develop guidelines, when using the widely accepted formal GRADE (Grading of Recommendations Assessment, Development, and Evaluation) system.Methods: To account for panel level factors and individual level factors, we employed two level hierarchical, random-effect, multivariate logistic and ordered logistic regression analysis.Results: 101 participants taking part in 8 CPGs panels issued 1,289 recommendations. Association of GRADE (normative) factors with the strength of recommendations (SOR) dominated the findings over the non-GRADE (descriptive) factors. In the main analysis certainty in evidence (regardless of direction for or against intervention) [OR=1.83 (95CI% 1.45 to 2.31;p<0.0001)], balance of benefits and harms [OR=1.49 (95CI% 1.30 to 1.69;p<0.0001)] and variability or uncertainty in the patients' values and preferences [OR=1.47 (95CI% 1.15 to 1.88;p<0.002)] were the strongest predictors of SOR coded as “neither for nor against” , “weak for or against” or “strong for or against” health intervention. Greater judgment of certainty of evidence proved highly associated with a strong recommendation [OR=3.60 (95% CI 2.16 to 6.00;p<0.00001] when panel members were issuing recommendation “for” interventions. When, however, panels made recommendations “against” intervention, certainty in evidence was not associated with probability of issuing strong recommendation [OR=0.98 (95%CI: 0.57 to 1.8; p=0.94)]. Two panelist characteristics were associated with strong recommendations: age (per decade) [OR=1.79 (95 CI% 1.2 to 2.84; p<0.005)], and greater intolerance of uncertainties [OR=0.57 (95 CI% 0.37 to 0.86; p<0.008)]. Agreement between individual panel members and the group ranged from very poor (average kappa of -0.01 in one panel) to moderate (kappa=0.64 in another panel), with most panels in an intermediate range. We also found that the panel members who were asked by the ASH to recuse themselves from voting due to high risk of conflict of interest (COI) would have voted differently if they were allowed to do so.Conclusion: Factors associated with GRADE's conceptual framework proved, in general, highly associated with strong versus weak recommendations and with the direction of recommendation. However, some non-GRADE factors of importance for decision-making were also identified. Findings that panel members with high risk of COI made different judgments than those without COI provide empirical support for the importance of managing conflict of interest. The low agreement between individual panel members and group consensus, and failure of certainty of evidence to be associated with strength of recommendations against an intervention, suggest the need for improvements in the process. DisclosuresCuker:Synergy: Consultancy; Genzyme: Consultancy; Kedrion: Membership on an entity's Board of Directors or advisory committees; Spark Therapeutics: Research Funding.

Trends of Splenectomy in Pediatric Patients with Immune Thrombocytopenia before and after the ASH 2011 Evidence-Based Practice Guidelines

Background: Immune thrombocytopenia (ITP) is an autoimmune disorder which affects 1 in 10,000 children. Thrombocytopenia occurs largely due to rapid destruction of antibody sensitized platelets in the reticuloendothelial system. While spontaneous resolution is commonly seen in acute ITP, treatment of chronic or persistent ITP is controversial and could pose as management challenges for clinicians. Splenectomy increases platelet survival by removing a common site of platelet destruction and has a 70-80% response rate, however, published literature is conflicting regarding its ideal timing. Furthermore, it is an invasive procedure with significant risk of infections, venous thromboembolism. In 2011, the American Society of Hematology (ASH) published revised clinical practice guidelines for the management of ITP (Neunert C et al. Blood 2011). Splenectomy was recommended in patients with severe symptomatic ITP with significant or persistent bleeding refractory to intravenous immunoglobulin (IVIG), corticosteroids, and anti-D therapy. It is unclear if the rates of splenectomy have changed since the publication of these guidelines. Using a large population-based estimate, we aimed to study the trends of splenectomy in pediatric patients with ITP, and the factors predicting the procedure in this population.Methods: We used discharge data from the National (Nationwide) Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality (AHRQ). Pediatric patients (age ≤ 18 years) hospitalized with ITP from 2005-2014 were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD9-CM) code 287.31. Cases of total splenectomy were identified using ICD9-CM procedure code ‘41.50‘. To calculate estimated trends of splenectomy, Cochran-Armitage trend test was used. Chi-square test, Mann-Whitney U test, survey logistic regression and hierarchal regression were used for analyses. Weights provided by NIS were used to calculate national estimates. A p-value < 0.05 was considered significant. All analyses were performed using SAS 9.4 (SAS Institute Inc., Cary, NC, USA).Results: The NIS data included 62 million weighted pediatric hospitalizations between 2005 and 2014 (unweighted admissions n=13 million). After excluding patient transfers, a total of 40,998 weighted hospitalizations with ITP occurred during this time-period. Total splenectomy was performed in 1,009 patients. Splenectomy rate showed a decline prior to revised guidelines: 3.3% (2005-06) to 2.3% (2011-12). It continued to decline further after the publication: 1.6% (2013-14), p <0.0001. Similar trend was noted for patients < 5 years of age: 10.6% (2005-06), 5.2% (2011-12), and 3.5% (2013-14), p <0.001. None of the other patient ages (5-10, 11-15, and 16-18), gender, or hospital regions showed consistent splenectomy trend in either direction. Multivariable analysis showed one year increase in patient age significantly increased adjusted odds of having splenectomy (odds ratio, OR 1.18, 95% confidence interval, CI 1.14-1.22, p <0.0001). Having an intracranial bleed also significantly predicted splenectomy (OR 5.16, 95% CI 1.96- 13.61, p=0.0009). Splenectomy was more commonly done in patients from Midwest (OR 2.83, 95% CI 1.19-6.74, p= 0.02) and South region (OR 1.89, 95% CI 1.02-3.51, p=0.04) compared to Northeast region. Mortality rate was similar between patients who received splenectomy and who did not.Conclusion: Overall, splenectomy rates showed consistently downward trend in pediatric patients with ITP between 2005 and 2014. Reduction in splenectomy rates in children <5 years of age could be due to increasing awareness for sepsis secondary to asplenia. Presence of severe bleeding (e.g. intracranial bleeding) in patients with ITP predicted splenectomy, which is consistent with ASH recommendations. Declining splenectomy rates in last 3 years since ASH guidelines release could mean that more patients receive medical management initially as recommended by ASH. However, due to possible under-coding for IVIG, corticosteroids, and anti-D and lack of longitudinal data, we were unable to study the association between prior treatment and splenectomy. Future studies should revisit the role of splenectomy in ITP with advent of novel therapeutic options such as thrombopoietin receptor agonists. DisclosuresNo relevant conflicts of interest to declare.

Safety and Efficacy of Thrombopoietin Receptor Agonists in Patients with Previously Treated Chronic Immune Thrombocytopenia: A Systematic Review and Meta-Analysis

Background: The current American Society of Hematology guideline recommends the use of thrombopoietin receptor agonists, eltrombopag or romiplostim as one of the second-line therapies for chronic immune thrombocytopenia (ITP). The efficacy and safety of those drugs have been tested in several clinical trials. However, the safety profile was not consistent throughout trials and is not yet well understood. We herein conducted a meta-analysis of randomized control trials to compare the safety and efficacy of thrombopoietin receptor agonists; eltrombopag and romiplostim versus placebo in patients with previously treated chronic ITP. Our primary outcome was drug-related adverse events greater than CTCAE grade 3.Methods: We performed a literature search in MEDLINE, EMBASE, Cochrane library, and the American Society of Hematology website up to September, 2015 by two independent authors according to PRISMA guideline. We included only randomized clinical trials comparing eltrombopag or romiplostim versus placebo. Random-effects model was used to estimate pooled odds ratio (OR) with 95% confidence interval (CI).Results: A total of eight trials involving 834 participants were included in the analysis. There was no significant difference of grade 3 or higher adverse events between placebo and treatment group (OR=1.01, 95% CI=0.57-1.78). Thromboembolism (OR=0.59, 95% CI=0.20-1.73), elevated ALT (OR=0.68, 95% CI=0.26-1.74), headache (OR=1.26, 95% CI=0.90-1.78), nausea (OR=0.82, 95% CI=0.43-1.55), or fatigue (OR=1.13, 95% CI=0.65-1.91) did not show a significant difference between groups, either. Clinical response, which is defined as platelets ≥50,000/μL at least once on treatment was significantly better in treatment group than in placebo group (OR=0.10, 95% CI=0.07-0.15). Bleeding symptoms (WHO Grades 1-4) were significantly more frequent in the placebo group (OR=1.60, 95% CI=1.14-2.24) during treatment.Conclusions: Although several studies have suggested clinically significant treatment-related adverse events, such as thromboembolism, this meta-analysis showed that thrombopoietin receptor agonists are safe, well-tolerated, and effective in patients with previously treated chronic ITP. DisclosuresNo relevant conflicts of interest to declare.

Appropriateness of testing for heparin-induced thrombocytopenia in hospitalized patients.

252 Background: Heparin induced thrombocytopenia (HIT) is a devastating thrombotic complication of heparin therapy and occurs in 0.2 to 5% of patients receiving heparin products and is a clinicopathologic diagnosis. The American Society of Hematology Guidelines, recommend the use of the “4Ts” scoring system to determine the pre-test probability of suspected cases. Also, a presumptive clinical diagnosis of HIT must be followed by immediate cessation of all forms of heparin and initiation of alternate anticoagulation. Proper diagnosis and treatment can be difficult for medical and surgical clinicians, with implications for morbidity, mortality, patient safety, and cost. The Objective of this study was to assess the incidence and appropriateness of HIT testing at our institution before and after an educational session for clinicians. We hypothesized that our intervention would provide better quality care of patients with suspected HIT. Methods: First, a retrospective chart review was conducted for a 3-month period, in which we collected baseline patient and HIT-testing data. Next, an “in-service” type lecture was delivered on seven occasions to various hospitalist groups. Follow-up data for an additional 3-month period was collected after these sessions. Results: See Table. Conclusions: In this single-center study, our educational interventions were successful in reducing inappropriate HIT testing, and encouraging consultation with hematology colleagues. Future studies are needed to evaluate the utility of online teaching modules, electronic order sets,and applicability to other medical centers. [Table: see text]

Influence of the American Society of Hematology guidelines on the management of newly diagnosed childhood immune thrombocytopenia.

In 2011, the American Society of Hematology (ASH) published updated guidelines for the management of childhood immune thrombocytopenia (ITP) recommending management with observation alone when there are mild or no bleeding symptoms, regardless of platelet count. Little is known about practice patterns of newly diagnosed ITP in the United States. To understand the impact of management recommendations on practice patterns. Retrospective medical record review in the Children's Hospital of Philadelphia, a large, urban, pediatric tertiary care hospital in Philadelphia, Pennsylvania. The study involved 311 pediatric patients with newly diagnosed ITP managed between January 1, 2007, and December 31, 2012. Management type (observation alone vs pharmacotherapy) was determined via medical record review and electronic pharmacy data at diagnosis and within 6 months after diagnosis. Overall, 44.7% of patients were managed with observation alone at diagnosis, with a significant increase from 34.9% in 2007-2010 to 49.2% in 2011 (P < .02) and 71.1% in 2012 (P < .001). Of those treated, 99% were treated with intravenous immunoglobulin. In multivariable logistic regression, younger age (odds ratio, 0.92; 95% CI, 0.87-0.99), lower platelet count (odds ratio, 0.86; 95% CI, 0.83-0.89), and earlier period (2007-2010) of diagnosis (odds ratio, 0.17; 95% CI, 0.09-0.34) were significantly associated with increased odds of pharmacologic management. During 2010-2012, 20.8% of patients were also treated within 6 months after diagnosis. There was no significant difference by year or initial management type in those who received this later pharmacotherapy. Additionally, 19.6% of patients had documented bleeding symptoms beyond cutaneous bruising or petechiae at diagnosis. Intracranial hemorrhage at diagnosis was rare (0.6%). We demonstrated a significant practice change in the management of newly diagnosed ITP at a pediatric care tertiary care hospital in the United States surrounding revision of the ASH management guidelines for childhood ITP. Our experience supports adoption of observation alone for a proportion of patients with newly diagnosed childhood ITP. This form of management did not lead to an increase in later treatment or an increase in delayed bleeding symptoms.

ITP and international guidelines: What do we know, what do we need?

In the last decade, rituximab and thrombopoietin-receptor agonists (TPO-ra) have been introduced into the traditional armamentarium of Immune Thrombocytopenia (ITP), consisting in corticosteroids as initial treatment and splenectomy in those not responding or relapsing. A variety of immunosuppressive treatments were reserved for patients not responsive to splenectomy. These advancements have been incorporated in two international current guidelines: the first, produced by an international group of expert clinicians (International Consensus Report, ICR); the second, by a selected group of hematologists and methodologists with expertise in systematic reviews and guideline development, mainly from United States, without direct connection with pharmaceutical companies. This latter guideline was endorsed by the American Society of Hematology (ASH). A new standardized terminology has also been adopted, with a more clear definition of primary vs secondary ITP and a clear distinction between the different phases of the disease-newly diagnosed, persistent, chronic (after 12 months from diagnosis). Both guidelines structure their suggestions on first, second and third-line treatments, with less attention to the different phases of the disease and its severity. There is a substantial agreement in proposing the initial treatment with oral corticosteroids and TPO-ra as third-line approach in patients unsuccessfully splenectomized in whom these agents appear to have the more favorable therapeutic profile. As to the second-line approach in patients failing corticosteroids, rituximab and TPO-ra could be valid alternatives to splenectomy but, unfortunately, the international guidelines fail to offer a consistent approach. Whereas ICR considers splenectomy at the same level of many other second-line treatments including rituximab and TPO-ra, ASH guideline definitely recommends reserving TPO-ra and rituximab to patients failing or with a contra-indication to splenectomy. As new data are being accumulated on long-term outcomes and toxicity of TPO-ra and the role of rituximab is being better defined for particular patients as second-line therapy, it will be possible to revisit the pros and cons of these options vs each other and splenectomy which, although less and less popular, maintains the highest curative potential, with an acceptable toxicity. The thrombotic risk in ITP should also be better defined and taken into account in guiding the treatment in the individual patients. Hopefully, new studies will be based more on clinical outcomes than on platelet count increase. The ultimate lesson of the insufficient evidence and disagreement among experts is that management of ITP should be tailored to the individual patients.

Management of Primary Immune Thrombocytopenia, 2012: A Survey of Oklahoma Hematologists-Oncologists

BackgroundManagement options for patients with primary immune thrombocytopenia (ITP) have increased, and treatment of patients with ITP has changed during the past 10 years. MethodsTo document current practice and to determine how current practice is related to recommendations of 2 recent practice guidelines for ITP, an international Consensus report and an American society of Hematology (ASH) guideline, the authors surveyed practicing hematologistsoncologists in Oklahoma. Surveys were specific for children or adults. Each survey had 3 questions describing patients with a new diagnosis and patients who had not achieved remission with initial treatment. Questions were adapted from the clinical scenarios of the ASH guideline. ResultsTwelve (92%) Oklahoma pediatric hematologistsoncologists responded; 82 (81%) Oklahoma adult hematologistsoncologists responded. For a child with a new diagnosis of ITP, a platelet count of 8000/μL and minor bleeding, 5 (42%) hematologistsoncologists selected observation without drug treatment (recommended by both guidelines). For an adult with a platelet count of 9000/μL who had failed to respond to initial treatment with corticosteroids and IVIg, 32 (39%) selected splenectomy (recommended by the ASH guideline); 30 (37%) selected rituximab and 13 (16%) selected thrombopoietin-receptor agonists (both recommended by the International Consensus report). Hematologists-oncologists who had more years in practice were more likely to select splenectomy (P = 0.047). ConclusionsIn a time of changing management for patients with ITP, these data document reported current management in Oklahoma and provide a basis for serial comparisons across time and for comparisons with other regions and comparison of management with patient outcomes.

Rituximab As Second-Line Treatment For Chronic Immune Thrombocytopenia: Investigator-Initiated Clinical Trial In Japan

The American Society of Hematology guidelines recommend rituximab as second-line treatment, as well as splenectomy and thrombopoietin receptor agonists (TPO-RAs), for chronic immune thrombocytopenia (ITP). However, rituximab has not been approved for the treatment of chronic ITP in Japan. To establish chronic ITP as a new indication for rituximab, we conducted an investigator-initiated clinical trial to clarify the efficacy and safety of rituximab for Japanese patients with ITP.This study was designed as a single-arm, multicenter phase III study. Patients diagnosed with chronic ITP who were previously treated with at least one therapy for ITP and whose platelet count was ≤ 30,000/μL were included. Patients with a past history or current hepatitis B virus, hepatitis C virus or HIV infection, who were treated with splenectomy within 12 weeks or with TPO-RA within 4 weeks were excluded. Rituximab at a dose of 375 mg/m2was intravenously infused once weekly for 4 weeks. Patients were premedicated with acetaminophen, restamin and hydrocortisone to prevent infusion reactions. Platelet counts, bleeding symptoms, and B lymphocyte counts were observed once monthly following the protocol. The primary endpoint was the proportion of patients whose platelet count was ≥ 50,000/μL 24 weeks after treatment with rituximab.Between October 2011 and January 2013, 26 patients were enrolled in this study from 10 hospitals in Japan. Median age of the patients was 40 years and 89% were female. Baseline platelet counts were 23,000/μL. Median interval from diagnosis of ITP to commencing rituximab therapy was 5.9 years. Previous treatment of ITP was corticosteroids (69%), splenectomy (15%), TPO-RA (27%) and intravenous immunoglobulins (39%). At baseline, 58% of patients had some bleeding symptoms. Median number of previous ITP treatments was two. All patients completed the study. At 24 weeks after treatment, 30.8% (95% CI: 14.3–51.8%) of patients achieved platelet counts > 50,000/μL. Seven of eight responders demonstrated improvement until 8 weeks. Platelet count was significantly increased compared with baseline (P<0.001). No unknown severe adverse events were observed. Subgroup analyses showed that ITP duration was numerically associated with the efficacy rate (46% vs 15% for duration< median vs ≥ median, respectively). Bleeding symptoms measured with the WHO bleeding scale were improved compared with baseline.We demonstrated the efficacy and safety of rituximab in Japanese patients with chronic ITP. The response rate was similar to that in previous reports in the US and Europe. We plan to propose that the Japanese government approve chronic ITP as a new indication for rituximab. Disclosures:Miyakawa:Fuji film: Consultancy; Alexion pharmaceuticals: Honoraria; GlaxoSmithKline: Consultancy, Honoraria; KyowaHakkoKirin: Consultancy, Honoraria; Shire: Honoraria. Off Label Use: rituximab, clinical trial. Nishiwaki:Chugai pharmaceutical: Research Funding; Zenyaku Kogyo: Research Funding. Higashihara:Alexion: Honoraria; Asahi Kasei Pharma: Honoraria; Janssen pharma: Honoraria, Research Funding; Takeda: Honoraria; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Shionogi: Honoraria, Research Funding; Nippon Shinyaku: Honoraria, Research Funding; GlaxoSmithKline: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Chugai: Honoraria, Research Funding; KyowaHakkoKirin: Honoraria, Research Funding; Boehringer-Ingeheim: Honoraria; Daiichi Sankyo: Honoraria; Yakurt: Honoraria; Astellas: Research Funding; Pfizer: Research Funding; Teijin: Research Funding; Meiji Seika pharma: Research Funding; Venesis: Research Funding; Baxter: Research Funding; Torii pharmaceutical: Research Funding; Bristol-Myers Squibb: Research Funding; Dainippon Sumitomo: Research Funding; Taiho: Research Funding; Taisho Tomiyama: Research Funding; MSD: Research Funding. Nishikawa:Daiichi-Sankyo: Research Funding. Ozaki:Chugai pharmaceutical: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Kyowa Hakko Kirin: Honoraria. Kanakura:Alexion Pharmaceuticals: Research Funding, Speakers Bureau. Okamoto:Novartis : Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; GlaxoSmithKlein: Honoraria, Research Funding; KyowaHakkoKirin: Honoraria, Research Funding; Chugai: Honoraria, Research Funding.

Influence Of Updated ASH Guidelines On Practice Patterns In Management Of Newly Diagnosed Childhood ITP, 2007-2012

▪ BackgroundTreatment recommendations for childhood Immune Thrombocytopenia (ITP) in the United States have been a subject of much debate. In early 2011, the American Society of Hematology (ASH) updated their guidelines, recommending that children with ITP be managed with observation alone when there is mild or no bleeding symptoms regardless of platelet count, reserving hospitalization and pharmacologic treatment for those with significant bleeding. The objective of this study was to better understand the impact these recommendations have had on practice patterns at a large, urban, pediatric tertiary care hospital in the United States. MethodsWe examined data from patients aged 0-17 with newly diagnosed ITP seen in inpatient and outpatient locations at the Children's Hospital of Philadelphia (CHOP) between January 1, 2007 and December 31, 2012. A cohort was developed by querying the hospital data system for all patients treated 2007-2012 using the ICD-9 code for ITP (287.31). Chart review was used to exclude patients with alternative diagnosis for thrombocytopenia, diagnosis prior to the time of interest, and initial treatment elsewhere. We compared management strategies at diagnosis and retreatment rates in the first 6 months after the initial diagnosis. The primary outcome, management at diagnosis, was analyzed by logistic regression and chi square analysis. Results502 unique patients were identified. After chart review, an evaluable cohort of 313 patients with newly diagnosed ITP remained. The most common reasons for elimination were an alternative diagnosis (n=41), diagnosis in a previous year (n=68), and initial treatment at another hospital (n=69). Of those with an alternative diagnosis, Evan's syndrome (n=8) and ALPS (n=5) were the most common reasons for elimination. New diagnoses per year ranged from 34-51 in 2007-2009 and 60-63 in 2010-2012. The mean platelet count and age at diagnosis were 16.9 x10^9/l and 6.22 years old, respectively. Distribution was skewed toward lower platelet count and younger age. Overall, 19.5% of patients were noted to have bleeding symptoms beyond bruising or petechiae. The most common bleeding symptoms at presentation were epistaxis (n=25), wet purpura (n=20), gastrointestinal bleeding (n=5), hematuria (n=4), and menstrual bleeding (n=4). Intracranial hemorrhage was rare (n=2, 0.6%). Overall, 55% of patients were managed with pharmacologic treatment at diagnosis. Of those treated, 98% were treated with IVIG. Additionally, the proportion of patients observed at diagnosis rose significantly during this time period from 34% of patients in 2007-2010 to 49.2% in 2011 (p<.02) and 72% in 2012 (p<0.001). Via logistic regression, younger age, lower platelet count, and year of diagnosis were significantly associated with increased odds of pharmacologic treatment. During 2010-2012, 21% of patients were also treated within 0.25-6 months after diagnosis, with no significant difference by year or initial management (p>0.5). The majority treated after diagnosis were due to “low platelet counts” (n=14), bruising/wet purpura (n=6), or parental anxiety/activity level (n=3). One child, initially treated with IVIG, presented with ICH secondary to trauma 1.5 months after diagnosis.ConclusionsOver time, a significantly increased proportion of patients were observed at diagnosis. Though we cannot prove causation, this change demonstrates a strong association between timing of ASH recommendations and increase in observation rates. As we increased the proportion of children being observed at diagnosis we did not see an increase in the proportion of children receiving treatment or those with significant bleeding symptoms in the following 6 months. Additionally, we found that 37% of patients originally identified via ICD-9 code did not meet our criteria for evaluation of ‘newly diagnosed ITP'. As there is a greater shift to observing patients, along with the development of outpatient infusion services, inpatient databases could become skewed in regard to ITP. Because of this, caution should be utilized in using ICD-9 code alone to identify new diagnoses, especially when chart review is not accessible. Future studies will be able to identify the changing national trend in admission and management and whether adoption of ASH guidelines is widespread. Disclosures:Lambert:Amgen: Research Funding; Nestle: Consultancy; GSK: Research Funding.▪ [Display omitted]

Conflicts of Interest and Clinical Recommendations

The growing influence of practice guidelines has increased concern for potential sources of bias. Two recent guidelines for primary immune thrombocytopenia (ITP) provided a unique opportunity for a systematic comparison of different methods of practice guideline development. One guideline (International Consensus Report [ICR]) was supported by pharmaceutical companies that produce products for ITP. The ICR panel members were selected for expertise in ITP; 16 (73%) reported associations with pharmaceutical companies. The other guideline was sponsored by the American Society of Hematology (ASH); panel members were selected for lack of conflicts and for expertise in guideline development as well as for ITP. Discrepancies were conspicuous when the guidelines addressed treatment. In contrast to the ASH guideline, the ICR gave stronger recommendations for agents manufactured by companies from which the ICR or its panel members received support. These data provide direct evidence that differences in financial support and methods of evidence evaluation can influence recommendations.

Management of Primary Immune Thrombocytopenia, 2012: A Survey of Oklahoma Hematologists-Oncologists

Abstract 1094 IntroductionWith the availability of multiple new agents, management of patients with primary immune thrombocytopenia (ITP) has changed substantially since the initial practice guideline for ITP was developed by the American Society of Hematology (ASH). To document current practice and to determine how current practice is related to recommendations of 2 recent guidelines for ITP, an International Consensus report (ICR), 2010, and an updated ASH guideline, 2011, we surveyed practicing hematologists-oncologists in Oklahoma. MethodsSeparate surveys were developed for children and adults. Each survey had 3 clinical scenarios; each scenario had 5–7 management choices. Hematologists-oncologists were instructed to select 1 management choice. Questions were adapted from the clinical scenarios of the ASH guideline. Additionally, data were collected for [1] number of years in practice; [2] site of practice, (either University of Oklahoma Medical Center or community); and [3] the estimated number of patients with ITP seen each year. Oklahoma hematologists-oncologists were identified by searching the Oklahoma Board of Medical Licensure and the Oklahoma Osteopathic Association websites for all active physicians certified in adult/pediatric hematology/oncology as of 12/31/2011. Exclusion criteria were: physicians whose careers were devoted to full-time research/administration. Data was collected between 1/31/2012–3/15/2012. Only the stronger grades of recommendations by the ICR and ASH guidelines were used for comparison to the hematologists-oncologists’ responses. Comparison of treatment responses to the number of years in practice was selected a priori, because it was hypothesized that hematologists-oncologists with fewer years in practice may more readily accept newer treatments while hematologists-oncologists with more years in practice may prefer more traditional management. Chi-square or Fisher’s exact test were used to determine if treatment responses differed by number of years in practice. SAS version 9.2 was used; alpha was set at 0.05. ResultsAll 13 (100%) Oklahoma pediatric hematologists-oncologists responded. For a child with a new diagnosis of ITP, a platelet count of 8,000/μL, and minor bleeding, 5 (38%) pediatric hematologists-oncologists selected observation without drug treatment (recommended by both guidelines). Because of the small number of pediatric hematologists-oncologists, no comparison of their responses to years in practice was performed. Eighty-three (82%) adult hematologists-oncologists responded. For an adult with a platelet count of 9,000/μL who had failed to respond to initial treatment with corticosteroids and IVIg, 32 (39%) selected splenectomy (recommended by ASH guideline); 31 (37%) selected rituximab and 13 (16%) selected thrombopoietin (TPO)-receptor agonists (both recommended by ICR). There was not a statistically significant difference between the number of years in practice for those who selected splenectomy versus all other treatment options (p = 0.07). DiscussionAlthough both recent guidelines recommended that children with no/mild bleeding may be managed with observation regardless of the platelet count, only 5 (38%) pediatric hematologists-oncologists selected observation in this scenario. The practice guidelines have different recommendations for second-line treatment in adults: the ICR recommends TPO-receptor agonists and rituximab but not splenectomy; the ASH guideline recommends splenectomy but not TPO-receptor agonists or rituximab. For this clinical scenario, 39% of hematologists-oncologists selected splenectomy, 37% selected rituximab and 16% selected TPO-agents. These different choices and recommendations reflect the changing clinical practice. Although not statistically significant, the hematologists-oncologists who had been in practice for >20 years appeared to be more likely to select splenectomy (p=0.07), consistent with greater acceptance of newer treatments by younger hematologists-oncologists. Although these data may not be generalizable, the high survey response rate provides confidence that these data accurately reflect the judgment, if not the actual practice, of Oklahoma hematologists-oncologists. ConclusionThese observations provide an estimate of actual current clinical practice for management of patients with ITP. Disclosures:Off Label Use: Rituximab for primary immune thrombocytopenia (ITP). George:Alexion, Inc.: Consultancy; Baxter, Inc.: Consultancy; Amgen, Inc.: Consultancy, PI for clinical trial involving romiplostim, PI for clinical trial involving romiplostim Other, Research Funding. Terrell:Amgen, Inc.: Consultancy; Baxter, Inc.: Consultancy.