ALBERT

Description: Venous thromboembolism (VTE) is increasingly diagnosed among individuals with hematologic malignancies. However, the risk of VTE among patients undergoing hematopoietic stem cell transplantation (HSCT) is unclear. We examined the incidence and risk factors for VTE and bleeding among 1514 patients undergoing in-patient HSCT. No protocolized VTE prophylaxis was used. By HSCT day 180, 75 symptomatic VTE occurred in 70 patients (4.6%; 95% confidence interval [CI], 3.6%-5.8%). Fifty-five (3.6%) were catheter-associated, 11 (0.7%) were non–catheter-associated deep venous thromboses, and 9 (0.6%) were pulmonary emboli. Thirty-four percent of VTE occurred at a platelet count less than 50 ×109/L; 13% occurred at a platelet count less than 20 ×109/L. In multivariate analysis, VTE was associated with prior VTE (odds ratio [OR], 2.9; 95% CI, 1.3-6.6) and with graft-versus-host disease (GVHD; OR, 2.4; 95% CI, 1.4-4.0). Clinically significant bleeding occurred in 230 patients (15.2%; 95% CI, 13.4%-17.1%); 55 patients (3.6%; 95% CI, 2.7%-4.7%) had fatal bleeding. Bleeding was associated with anticoagulation (OR, 3.1; 95% CI, 1.8-5.5), GVHD (OR, 2.4; 95% CI, 1.8-3.3), and veno-occlusive disease (OR, 2.2; 95% CI, 1.4-3.6). In HSCT patients, VTE is primarily catheter-related and 3-fold less common than clinically significant bleeding. These findings warrant consideration when selecting VTE prophylaxis in HSCT patients.

Description: Introduction : Knowing the prevalence of ITP is important to determine the burden of this rare disease. Multiple new thrombopoietin agonists are being developed for the treatment of ITP, despite the paucity of reliable and generalizable estimates of ITP prevalence. Only two studies have previously reported the prevalence of ITP in the United States (US) (the only other prevalence estimate focused on children with chronic ITP in the United Kingdom). Segal et al (J Thromb Haemost2006; 4:2377–2383) report a one-year age adjusted prevalence of 9.5 per 100,000 persons aged 1–64 years; Feudjo-Tepie et al (J Thromb Haemost2008; 6:711–712) report a one-year prevalence of adult chronic ITP of 23.6 per 100,000 adults 318 years of age. Both studies based their estimates on private insurance claims data. The goal of this study was to determine the prevalence of ITP in all patients in the State of Oklahoma, regardless of insurance status and age. Methods : Similar to the previous 2 studies, the ICD-9-CM code of 287.3 was used to identify ITP. Unlike the previous 2 studies, we obtained data directly and entirely from hematologists. In November 2007, there were 93 hematologists in Oklahoma who cared for ITP patients. Our preliminary data documented that hematologists saw 3 92% of all patients with ITP and that primary care physicians in Oklahoma reported they were ‘likely’ to refer 85% of patients with platelet counts

Description: Background: We undertook a large multisite observational study collecting prospective data on health care utilization of patients with sickle cell disease (SCD). No prospective examination of symptom burden has been undertaken in SCD since the Cooperative Study of Sickle Cell Disease, and none in the modern era, since the widespread adoption of hydroxyurea therapy. The ESCAPED trial aims to compare patient centered outcomes following management of acute painful vaso-occlusive (VOC) events in the emergency department or in the infusion center. Here, we examine acute care utilization patterns in the first 223 subjects who have completed at least 6 months of follow-up and test determinants of utilization. Methods: This is an ongoing, prospective cohort study that is recruiting across four sites (Baltimore, Cleveland, Milwaukee, and Baton Rouge). 500 adults with SCD who live in proximity to one of the study sites are being recruited and followed for 18 months. Data from visits for all acute, uncomplicated VOC are collected by chart review and patient interview. To ensure that acute visits are not missed, subjects are contacted on a monthly basis and where available statewide health information exchanges are queried. We tested for associations between subject characteristics upon enrollment and the number of acute visits during follow up using Poisson regression. Results: The average length of follow-up to date is 9.1 months with a range of 6.1-14.2 months for the 223 subjects who have been enrolled for at least 6 months. The mean number of acute visits per month for uncomplicated VOC by the cohort was 0.65 (SD 0.87) with a median of 0.35, minimum of 0 and maximum of 5. 43 subjects have had no acute visits. 59% of the cohort are female, the mean age is 35.6 (SD 12.1). 74.3% have sickle cell anemia, 42% are employed and 52% reported having chronic pain. In a multivariate model, factors associated with an independent decrease in likelihood of an acute visit were increasing age, a history of leg ulcers, graduating high school and being employed, while an increase in likelihood of an acute visit was associated with chronic complications (kidney disease, retinopathy, stroke, and avascular necrosis) and chronic pain. Conclusions: In this cohort, chronic complications like renal disease and AVN are associated with increased acute care visits. The association of chronic pain as an independent risk factor for acute visits, while intuitive, suggests that understanding and managing chronic pain may be central to mitigating pain and decreasing the need for acute care visits in the long term. The prevalence of chronic pain is high in this cohort, which likely well represents the contemporary US sickle cell community. The development of therapeutic strategies that address this significant complication of SCD are imperative if we are to both decrease symptom burden and the need for health care utilization in this population. Disclosures Lanzkron: NKT therapeutics: Research Funding; Prolong: Research Funding; Pfizer: Research Funding; Selexys: Research Funding; NHLBI: Research Funding; PCORI: Research Funding; GBT: Consultancy. Haywood:PCORI: Research Funding; NHLBI: Research Funding. Little:PCORI: Research Funding. Field:PCORI: Research Funding; NKT Therapeutics: Consultancy, Research Funding; Astellas Pharma: Consultancy, Research Funding. Shows:PCORI: Employment, Research Funding. Segal:PCORI funded: Research Funding. Saheed:PCORI: Research Funding. Robertson:PCORI: Research Funding. Proudford:PCORI: Research Funding. Kincaid:PCORI funded: Research Funding. Burgess:PCORI: Research Funding. Green:PCORI: Research Funding. Wang:PCORI: Research Funding. Seufert:PCORI: Research Funding. Brooks:PCORI: Research Funding. Griffin:PCORI: Research Funding. Piehet:PCORI: Research Funding. Frymark:PCORI: Research Funding. Varadhan:PCORI: Research Funding.

Description: Background: Patients with sickle cell disease (SCD) suffer from frequent vaso-occlusive crises (VOC), the leading cause of hospitalization and ED visits for these patients. Infusion centers (IC) are alternatives to ED care and may provide patients with a better care experience. We previously demonstrated in a single center that the use of such centers provides more rapid pain control and can decrease the risk of a hospital admission. For the management of VOC the NHLBI's guidelines recommend that patients receive analgesic therapy within 60 minutes of registration and that pain be reassessed every 15-30 minutes until it is controlled. In the ESCAPED study, we aimed to learn whether the ED or IC more rapidly provides analgesia to patients who present with an uncomplicated VOC. Methods: The ESCAPED study is a prospective cohort study that recruited subjects at four sites (Baltimore, Cleveland, Milwaukee and Baton Rouge). The Baltimore and Milwaukee sites have dedicated ICs that treat only adults with SCD; the Cleveland and Baton Rouge sites have ICs that treat a diverse group of patients requiring infusion services. Patients were enrolled during regular outpatient visits between 4/2015 and 12/2016. Uncomplicated crisis was defined as an acute episode of pain with no known other cause and required treatment with parenteral pain medications. Upon study entry, participants completed surveys to collect demographic data; chart abstraction was done for information on comorbidities. Data was extracted after the acute visits for the primary endpoint: time to first dose of pain medication. We also extracted data on reassessment of pain after the first dose of parenteral pain medication and admission or discharge status. Patients' comorbidities were updated through chart abstraction after each visit. Each participant was followed for 18 months and data from visits for acute, uncomplicated VOC were collected. All acute visits were recorded and complete data was collected for each patient from the first visit each month to each site of care for uncomplicated crisis. Time-varying propensity scores estimated by a random effects model was used to balance covariates in the two arms. The treatment effects were estimated using a sub-classification approach and standard errors were computed by nonparametric bootstrapping at the individual level. Results: 483 subjects were enrolled and 444 completed 18 months of follow up (29 withdrew, 10 died). The median follow-up was 8.2 months (IQR, 5.7-12.0) for the 39 subjects who did not complete the study. There were 4851 acute visits for uncomplicated VOC of which 2910 had the complete data collected. 1445 visits to an ED and 1465 visits to an IC. The mean number of visits per patient was 10.0 (SD, 15.5) and median number was 4 (IQR, 1-12.5). 115 subjects had no acute visits during the study period. In the adjusted analyses, the mean time to first dose of parenteral pain medications was 125 minutes in an ED setting and 63 minutes in an IC setting (95% CI, 54-69). Patients seen in an IC were significantly more likely to have their pain reassessed 30 minutes after their first dose of pain medication than patients treated in an ED (OR, 2.5; 95% CI, 2.1-3.0) and visits to the ED were significantly more likely to end in the patient being admitted than visits to the IC (OR, 5.9; 95% CI, 4.7-7.3). Conclusions: With adjustment for differences between patients treated in the ED and IC, we demonstrated that those treated in an IC have significantly better treatment experiences than subjects treated in an ED: a 50% reduction in time to first dose of pain medication and an almost 6-fold decrease in hospital admission. Increasing access to infusion clinics is essential to improving the quality of care of uncomplicated VOC in adults with SCD. Disclosures Lanzkron: GBT: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Prolong: Research Funding; NHLBI: Research Funding; PCORI: Research Funding; Selexys: Research Funding; Ironwood: Research Funding. Little:Doris Duke Charitable Foundations: Research Funding; PCORI: Research Funding; Hemex: Patents & Royalties: Patent, no honoraria; NHLBI: Research Funding. Field:Incyte: Research Funding; Ironwood: Consultancy, Research Funding; Prolong: Research Funding. Haywood:PCORI: Research Funding. Varadhan:PCORI: Research Funding. Saheed:PCORI: Research Funding. Proudford:PCORI: Research Funding. Robertson:PCORI: Research Funding. Kincaid:PCORI: Research Funding. Burgess:PCORI: Research Funding. Green:PCORI: Research Funding. Wang:PCORI: Research Funding. Seufert:PCORI: Research Funding. Brooks:PCORI: Research Funding. Piehet:PCORI: Research Funding. Griffin:PCORI: Research Funding. Arnold:PCORI: Research Funding. Frymark:PCORI: Research Funding. Huang:PCORI: Research Funding. Wallace:PCORI: Research Funding. Segal:PCORI: Research Funding.

Description: Background: Since the introduction of plasmapheresis, TTP-associated mortality has declined from 90% to 10–20%. However, 20–50% of patients experience recurrent disease. The goal of this study was to describe the clinical spectrum of TTP, determine the clinical outcome of patients with TTP and identify risk factors for disease relapse or recurrence. Methods: We retrospectively reviewed consecutive TTP patients treated between January 1992 and April 2008 at the Johns Hopkins Hospital. Complete demographic, clinical, laboratory, treatment, and response data were collected. A standard treatment protocol of corticosteroids (Methylprednisolone 100 mg IV q12h) and daily plasmapheresis (1.5 plasma volumes) was used during the study period. Rituximab, azathioprine and vincristine were employed in refractory or relapsing patients at physician’s discretion. Logistic regression was used to examine the association of clinical and laboratory parameters with four ordered outcome categories in TTP survivors: relapse (

Description: Background: Patients with immune thrombocytopenic purpura (ITP) infected with Helicobacter pylori (H. pylori) are often treated with antibiotics to eradicate infection and raise platelet counts. We aimed to systematically review the evidence regarding this practice to better quantify response rate. Study Design and Methods: We searched MEDLINE through April 2005, without language restriction; reviewed reference lists and queried experts for articles describing treatment of ITP with antibiotics targeting H. pylori. We included studies of any design involving more than 5 patients. Response rates were tabulated using the authors’ definitions, and pooled using a random effects model. Techniques of meta-regression were used to assess whether patient or study characteristics influenced response rates. Results: We retrieved 52 potentially eligible studies. Of these, 16 studies met our inclusion criteria. From 10 studies, we had individual level patient data. None of the studies was a controlled trial. The pooled response rate (both partial and complete responses) was 45% [95% confidence interval (C.I.) 32% to 58%]. The number of previous treatments (0–1, 2, 3 or more) influenced the response rate with an 18% (p=0.001) decline in response rate with each higher category; duration of disease did not independently predict response. In analyses of individual patient data, quartile of platelet count upon entry also influenced response rate; 58% of patients in the highest quartile responded compared to 34% in the lowest quartile (p=0.018). Conclusions: No randomized controlled trial has tested H. pylori eradication with antibiotics as a treatment for ITP. The sixteen observational studies we reviewed were fairly consistent with approximately half of treated patients having a platelet response to therapy. Without control groups, these studies do not provide strong evidence to support practice recommendations. However, given the low toxicity of antibiotic therapy, this treatment may be appropriate for patients who have not demonstrated refractoriness to multiple therapies. Response Rates by Number of Previous Treatments Response Rates by Number of Previous Treatments

Description: Whether the eradication of Helicobacter pylori infection can increase the platelet count in patients with immune thrombocytopenic purpura (ITP) is still a controversial issue. To provide evidence-based guidance, we performed a systematic review of the literature published in English, selecting articles reporting 15 or more total patients. We identified 25 studies including 1555 patients, of whom 696 were evaluable for the effects of H pylori eradication on platelet count. The weighted mean complete response (platelet count ≥ 100 × 109/L) and overall response (platelet count ≥ 30 × 109/L and at least doubling of the basal count) were 42.7% (95% confidence interval [CI], 31.8%-53.9%) and 50.3% (95% CI, 41.6%-59.0%), respectively. In 222 patients with a baseline platelet count less than 30 × 109/L, the complete response rate was 20.1% (95% CI, 13.5%-26.7%) and the overall response rate was 35.2% (95% CI, 28.0%-42.4%). The response rate tended to be higher in countries with a high background prevalence of H pylori infection and in patients with milder degrees of thrombocytopenia. These findings suggest that the detection and eradication of H pylori infection should be considered in the work-up of patients with seemingly typical ITP.

Description: Introduction Patients with sickle cell disease (SCD) suffer from frequent vaso-occlusive crises (VOC), the leading cause of hospitalization and emergency department (ED) visits for these patients. Patients and healthcare providers often report dissatisfaction with the quality of SCD pain management in the ED. Satisfaction has been defined as whether a patient's expectations about a health encounter were met. Infusion centers (IC) are alternatives to ED care for patients with VOC. The aim of this study is to describe adult patients' satisfaction with care for the treatment of uncomplicated VOC in EDs and ICs. Methods As part of a prospective cohort study (the ESCAPED study) comparing outcomes between ED and IC care for uncomplicated VOC, we conducted a descriptive analysis of patient satisfaction from the first acute visit of adult patients (〉18 years) who were recruited from 4 sites (Baltimore, Baton Rouge, Cleveland, Milwaukee) from April 2015 to December 2016. Demographic and clinical variables were collected via medical record review. Participants were provided with a survey about their satisfaction of care within 72 hours after their acute visit to the ED or IC. The survey tool included questions about overall satisfaction with quality of care and with pain treatment received, satisfaction with pain management, communication with clinicians including physicians and nurses, interpersonal aspects of care, clinician competence, involvement of family and friends, and access to care. Responses were scored on a 7-point Likert scale from very strongly agree to very strongly disagree, except for "access to care" items, which were binary and categorical. We dichotomized Likert scale responses by grouping positive responses (very strongly agree, strongly agree, and agree) as being satisfied, and negative responses (very strongly disagree, strongly disagree, disagree, and uncertain) as being dissatisfied. Descriptive statistics were computed using Mann-Whitney U test for continuous variables and chi-squared test for categorical variables. All hypothesis testings were 2-sided and p values were not adjusted for multiple comparisons. Results We enrolled 483 patients in ESCAPED and followed them for 18 months. We excluded 115 patients who did not have VOC visits during their observation period. Of the 368 patients with visits, 212 patients (58%) responded to the survey after their first acute visit: 89 (42%) had received care at an ED and 123 (58%) received care at an IC. Patients who received care at an IC were older, more likely to be married or with a significant other, and less likely to live alone. More patients who had a history of kidney disease received care at an IC than in an ED. Patients with higher numbers of ED visits in the previous year were more likely to seek care in an ED and those with higher numbers of IC visits in the previous year were more likely to seek care at an IC. The majority of patients (55%) in the ED responded to the survey by phone whereas the majority of patients (54%) in the IC responded to the survey in-person. Overall, patients who received care in an IC were more satisfied with the quality of care (95% vs. 73%, p〈 0.001) and with their pain treatment (93% vs. 66%, p〈 0.001) than patients who received care in an ED. (Table) Adults who received care at an IC were more satisfied with the pain management, communication with clinicians, interpersonal aspects of care, and clinician competence than adults who received care at an ED. The majority of patients in both groups (59%) came for care unaccompanied; ED-treated patients were more likely than IC-treated patients to agree that a companion helped improve the quality of care they received. Conclusions Patients who received care in an IC were more satisfied with their care and with the quality of their pain management than patients who received care from an ED. Increasing access to IC models of care can improve delivery of patient-centered care for VOC. Disclosures Brooks: PCORI: Research Funding. Wang:PCORI: Research Funding. Seufert:PCORI: Research Funding. Haywood:PCORI: Research Funding. Varadhan:PCORI: Research Funding. Saheed:PCORI: Research Funding. Segal:PCORI: Research Funding. Field:Incyte: Research Funding; Ironwood: Consultancy, Research Funding; Prolong: Research Funding. Frymark:PCORI: Research Funding. Little:Doris Duke Charitable Foundations: Research Funding; NHLBI: Research Funding; Hemex: Patents & Royalties: Patent, no honoraria; PCORI: Research Funding. Griffin:PCORI: Research Funding. Arnold:PCORI: Research Funding. Shows:PCORI: Research Funding. Piehet:PCORI: Research Funding. Proudford:PCORI: Research Funding. Robertson:PCORI: Research Funding. Wallace:PCORI: Research Funding. Kincaid:PCORI: Research Funding. Green:PCORI: Research Funding. Burgess:PCORI: Research Funding. Lanzkron:Selexys: Research Funding; Pfizer: Consultancy, Research Funding; GBT: Consultancy, Research Funding; Prolong: Research Funding; NHLBI: Research Funding; PCORI: Research Funding; Ironwood: Research Funding.

Description: Introduction: Heparin-induced thrombocytopenia (HIT) is a syndrome in which anti-platelet factor 4/heparin antibodies (HITab) and thrombocytopenia develop after heparin exposure. While HIT is an established risk factor for arterial and venous thromboses, HITab, in the absence of thrombocytopenia, may also be a prothrombotic risk factor. As patients with chronic kidney disease on hemodialysis are chronically exposed to heparin, we hypothesized that the presence of HITab may contribute to the high rates of thrombotic disease and mortality in these patients. Patients and methods: We analyzed data from the CHOICE study, a prospective cohort study of incident dialysis patients. Clinical data were available from medical record review. Arterial cardiovascular events and events of vascular access occlusion were validated by chart review and adjudication. Venous thromboembolic events were defined by ICD-9 codes. Thrombocytopenia was defined as a platelet count 50% decline from a previous platelet count. Median duration of follow-up is 2.7 years. We measured HITab using a commercial ELISA assay in stored serum obtained 6 months after cohort enrollment of 740 participants (596 on hemodialysis, 144 on peritoneal dialysis). ELISA results were corrected for inter-plate variability. A positive HITab test associated with thrombocytopenia in the subsequent three months was considered compatible with HIT. We used techniques of logistic regression and of survival analysis with adjustment for potential confounders in our analyses. Results: 10.3% of all patients were positive for HITab at six months. HITab positivity was not associated with thrombocytopenia. HITab did not predict subsequent outcomes including cardiovascular (hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.65–1.41), vascular access occlusive (HR 0.82, CI 0.40–1.71), or venous thromboembolic events (HR 1.39, CI 0.17–11.5) and did not predict mortality (HR 1.00, CI 0.66–1.53). 9 patients (1.2%) had results compatible with HIT (thrombocytopenia + HITab). 1 patient with HIT (0.13%) had venous thrombosis yielding a hazard ratio of 13.7 (CI 1.63–115.5) for HIT and thrombosis. Conclusions: HITab seropositivity after six months of dialysis is frequent, but is not associated with thrombocytopenia. In end-stage renal disease patients treated by dialysis HITab seropositivity in the absence of thrombocytopenia is not an independent risk factor for cardiovascular morbidity or mortality. However, HIT may occur in this patient population and is associated with thrombosis.

Description: Background: The possibility of variation in platelet count by age and genetic background has not been examined. Identification of subpopulations with elevated platelet counts, within what is traditionally considered a normal range, may identify a group with excessive morbidity or mortality. Furthermore, platelet count differences may suggest populations in which genetic polymorphisms in regulatory proteins such as the thrombopoietin receptor influence platelet production. We hypothesized that there were differences in platelet count by ethnicity, sex and age not explained by environmental factors. Objective: To demonstrate differences in mean platelet counts by ethnicity, sex, and age while controlling for variables known to influence platelet count. Methods and Design: We used data from the National Health, Nutrition and Examination Survey III (NHANES III), which is a multistage probability sample of the United States population with data collected between 1988 and 1994. Using appropriate weighting for the complex sampling design, the geometric mean platelet count was calculated for the total population and the population stratified by ethnicity, sex, and age, while controlling for C-reactive protein, white blood cell count, iron-deficiency, serum folate, markers of alcohol intake, presence of hepatitis B or C antibodies, and diabetes mellitus. Other potential influences, such as medications, were found not to affect the predicted counts and not included in the models. Results: The lowest mean platelet counts were among whites (259 K/ml [95% C.I. 255–264 K/ml]) and the highest were in non-Hispanic blacks (275 K/ml [95% C.I. 270–280 K/ml]) with Mexican-Americans having intermediate values (266 K/ml [95% C.I. 261–272 K/ml]), when controlled for age and sex. Older men and women of each ethnicity consistently had lower mean platelet counts, with 60–69 years olds having mean counts approximately 7 K/ml lower than young adults (p=0.015) and 70–90 year olds having mean counts 19 K/ml lower than young adults (p