ALBERT

Description: Background: Patients with cancer are at elevated risk for venous thromboembolism (VTE). Active cancer contributes a 4-7 fold increased risk for VTE; however, the incidence of VTE stratified by subpopulations of patients diagnosed with cancer, especially race/ethnicity, is uncertain. Objective: Describe the incidence of VTE among adult patients (age ≥ 18 years) with a cancer diagnosis in Oklahoma County, OK according to age, gender, race, and cancer type. Methods: In collaboration with the Centers for Disease Control and Prevention, we established a population-based surveillance system for VTE in Oklahoma County, OK between April 1, 2012-March 31, 2014 to estimate the incidences of first-time and recurrent VTE events. The Commissioner of Health made VTE a reportable condition and delegated surveillance-related responsibilities to the University of Oklahoma, College of Public Health. Active surveillance involved reviewing imaging studies (e.g., chest computed tomography and compression ultrasounds of the extremities) from all inpatient and outpatient facilities in the county and collecting demographic, treatment and risk factor data on all VTE case-patients. Patients were linked to the Oklahoma Central Cancer Registry. Any patient with a cancer diagnosis since 1997, excluding basal or squamous cell carcinoma, were included in the population-at-risk. Active cancer was defined as metastatic or a diagnosis ≤6 months before their VTE diagnosis. Poisson regression was used to estimate incidence rates (IRs) and 95% confidence intervals (CIs), which are reported per 1,000 person years (PY). Estimates with

Description: Background: Compared to Whites, Black-Americans may have a 40% higher incidence of idiopathic VTE. However, whether other VTE characteristics vary by race is uncertain. Objective: To compare demographic and baseline characteristics among White- and Black-Americans with VTE. Methods: Using a standardized data-collection form, demographic and baseline characteristics were prospectively collected from consecutive consenting patients enrolled in seven Thrombosis and Hemostasis Centers from August 2003 to March 2008. For patients with objectively diagnosed VTE, demographic and baseline characteristics were compared among White- and Black-American VTE patients, both overall, and by age and gender. Results: Among 1960 White- and 368 Black-Americans with VTE, compared to Whites, Blacks had significantly less isolated DVT (73.9% vs. 86.5%, p

Description: A family history (FH) of thrombophilia may prompt a referral to a pediatric thrombophilia clinic. The International Society of Thrombosis and Haemostasis recommends a step-wise thrombophilia evaluation for children with venous thrombosis, but there are no screening recommendations for asymptomatic children with a FH of thrombophilia. There is limited data on how many children are evaluated by a pediatric hematologist for a FH of thrombophilia or how these children are managed. We utilized the Centers for Disease Control and Prevention (CDC) Thrombosis and Hemostasis Centers Pilot Sites Registry to characterize children without a personal history of thrombosis who are referred to Thrombosis Centers (TCs). The CDC initiated the registry between eight TCs, including four pediatric sites. We queried the database for pediatric subjects, who enrolled in the registry between August 2003-March 2006. Data collection included referral patterns, laboratory and radiological tests ordered, diagnosis, and treatments. Three hundred thirty-two subjects were identified, ages 0–17 years (average 9 years). Fifty-five (16.6%) have no personal history of thrombosis. Among the 55 asymptomatic children 4 (7.3%) were referred exclusively for a FH of thrombosis without thrombophilia, 12 (21.8%) were referred exclusively for a FH of thrombophilia without a FH of thrombosis, 11 (20.0%) were referred for a FH of both thrombosis and thrombophilia, and 28 (50.9%) did not have a FH of thrombosis or thrombophilia. The latter subjects may have been referred to the TCs for anticoagulation management or for evaluation of a condition associated with thrombophilia such as migraine. No asymptomatic subjects were referred from the in-patient setting, 48 (87.3%) were referred from the out-patient setting, and 7 (12.7%) were self-referred. Of the 55 asymptomatic children, 19 (34.5%) were referred with a prior diagnosis of thrombophilia. Table 1 compares testing at the TCs of symptomatic and asymptomatic subjects. Three asymptomatic subjects with a FH of thrombosis and thrombophilia received anticoagulation prophylaxis, and 3 subjects received a recommendation for prophylaxis for future high risk situations. In summary, 16.6% of children enrolled in the CDC registry have no personal history of thrombosis. A significant proportion of these asymptomatic children have testing for prothrombotic risk factors prior to referral and at the TCs. We are conducting research to determine who and when to screen for thrombophilia, potential complications of such testing, when to provide genetic counseling, and optimal clinical application of the results. Thrombophilia Testing at Pediatric Thrombosis Centers % subjects tested for Genetic tests Anticoagulants/Antiphospholipid antibodies Clotting factors Screening tests Lipids/Homocysteine All (n=332) 42.5 54.8 43.7 56.6 36.5 Symptomatic (n=277) 38.6 52.7 44.0 57.8 32.1 Asymptomatic (n=55) 61.8 65.5 41.8 50.9 58.2 Among asymptomatics with: FH of thrombosis (n=4) 100 100 25 100 100 FH of thrombophilia (n=12) 75 75 41.7 41.7 58.3 FH of thrombosis and thrombophilia (n=11) 72.7 63.6 27.3 36.4 81.8 No FH (n=28) 46.4 57.1 50 53.6 42.9

Description: Abstract 4219 Background: Clinical characteristics associated with abdominal vein thrombosis (including hepatic, portal, and mesenteric veins; renal veins; and inferior vena cava [IVC]) overlap with characteristics associated with deep vein thrombosis (DVT) in the legs and pulmonary embolism (PE) but also possess unique attributes. These characteristics may differ between adult and pediatric patient groups. Methods: Using a standardized data-collection form, demographic and baseline characteristics were prospectively collected from consecutive consenting patients enrolled within one of seven Thrombosis and Hemostasis Centers over a seven-year period, August 2003 to June 2010. Patients with intra-abdominal venous thrombosis (defined as abdominal and renal veins, and IVC) were divided into pediatric (age

Description: Abstract 2990 Poster Board II-966 Background: Venous thrombosis (VTE) is a rare disorder in children, and its overall incidence, pathophysiology, and outcomes remain poorly defined. Registries and cohort studies including those from Canada, Germany, Colorado, and others have provided seminal observations on the incidence, age distribution, associated conditions, diagnostic modalities, location, and treatment patterns for children and have resulted in greater awareness and improvements in clinical practice. Methods: The Division of Blood Disorders of the Centers for Disease Control and Prevention (CDC) in collaboration with eight Thrombosis and Hemostasis Centers Patient Registry began in August 2003 to characterize clinical features, treatments, and services provided to the individuals referred. Results: As of March 2009, 316 children and adolescents from birth to 21 years were enrolled at six of the sites. About half of the patients (48%) were referred from the inpatient setting. Patients were predominantly of white (84%) or black (13%) race and median age was 15.6 years (newborn-21 years). Patients were stratified by age; 178 (56%) were adolescents (≥15 years), 75 (24%) age 7 to 14, 38 (12%) age 1 to 6. 25 (8%) were infants (

Description: Background Hospital discharge data have been used to estimate the burden of venous thromboembolism (VTE) disease. However, most of these databases are de-identified which limits their utility for estimating VTE incidence due to the inability to identify multiple hospitalizations for the same VTE event, and the inability to differentiate between first-time and recurrent VTE events. Objective We aimed to estimate the magnitude of error in estimates of VTE incidence derived from hospital discharge data by comparing the results obtained when patient identifying information is included, thus enabling us to remove duplicate patient events and stratify by first-time and recurrent VTE events, to the estimates obtained using only de-identified data. Methods In collaboration with the Centers for Disease Control and Prevention (CDC) and the Oklahoma State Department of Health (OSDH), we established a pilot surveillance system for VTE events in Oklahoma County, OK during 2012–2014. The OSHD Commissioner of Health made VTE events reportable conditions from 2010 to 2015 which facilitated our acquisition of hospital discharge data with patient identifiers for years 2010–2012 from the OSDH. The data included the inpatient, outpatient surgical, and ambulatory surgery center discharges. A deep vein thrombosis diagnosis was defined as the presence of any of the ICD-9-CM codes 451.1x, 451.81, 451.83, 453.2, 453.4x, 671.3x, and 671.4x. A pulmonary embolism diagnosis was defined as the presence of either of the ICD-9-CM codes 415.1x and 673.2x. Data were de-duplicated and linked across datasets using Link Plus software incorporating patient identifying variables. Duplicate events for the same person caused by hospital transfers were defined a priori as a second hospital admission with a VTE diagnosis code occurring within 72 hours of the previous discharge date with a VTE present on admission (POA) code for the second admission of “Yes” or “Unknown.” Potentially recurrent events were defined as two hospital admissions of the same patient ≥72 hours apart with a VTE diagnosis. Census Bureau estimates for 2010–2012 were used to define the population at risk in Oklahoma County. Incidence rates (IR) and 95% confidence intervals (CI) were calculated using the Poisson distribution and reported as events per 100,000 population per year. Rate differences and excess fractions were calculated to account for the contribution of recurrent and duplicate events to overall estimates and to differentiate between event-based incidence estimates and patient-based estimates. Results We identified 3,299 unique patients with VTE events. The overall event-based IR for VTE events was 249 (95% CI: 241–257). The IR for potentially recurrent events was 35 (95% CI: 32–38) and for duplicate events caused by patient transfers was 13 (95% CI: 11–14). Thus, the rate difference between event-based estimates and patient-based estimates was 48 (95%CI: 44–51) giving a patient-based IR for first-time events of 201 (95% CI: 194–208). The excess fraction was 19.2% (95% CI: 17.8%-20.5%), of which 14.1% (95% CI: 12.9%–15.2%) is attributed to potential recurrent events and 5.1% (95% CI: 4.4%–5.8%) is attributed to duplicate events caused by patient transfers. Conclusions Using event-based estimates for VTE disease resulted in an over-estimate of the incidence rate of first-time VTE events by up to 20%. Included in this excess estimate is the burden caused by potential recurrent events (14%) and duplicate events caused by patient transfers (5%). We designed our case definitions to accurately measure first-time events, and to capture all duplicate events and potential recurrent events. Assuming these data are representative of national trends, applying these excess fractions to estimates from de-identified data may improve the validity of measuring the incidence of first-time VTE events from de-identified hospital discharge data. Disclosures Bratzler: Centers for Disease Control and Prevention: Consultancy; Sanofi Pasteur: Consultancy. Raskob:Bayer Healthcare: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Janssen Pharmaceuticals: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; ISIS Pharmaceuticals: Consultancy, Honoraria.

Description: Introduction: Venous thromboembolism (VTE), defined as deep vein thrombosis (DVT), pulmonary embolism (PE), or both, is an important cause of morbidity and mortality among hospitalized patients, with PE ranking among the most frequent undiagnosed acute diseases in medical practice (Adv Orthop,2010;2(1):8–14). Methods: Durham County, NC, has a population of ~280,000 individuals and is served by three hospitals, Duke University Medical Center (DUMC) and Duke Regional Hospital (DRH) that share an electronic medical record, and the Durham Veterans’ Administration Medical Center (VAMC). Autopsy service is performed primarily at DUMC and, much less frequently, at the Durham VAMC. We performed a retrospective review of all autopsies performed at DUMC during a two year period (April 1st 2012 through March 31st 2014). Individuals living outside of Durham County were excluded. We also excluded autopsies performed on fetuses and neonates less than one month of age, as well as autopsies that were limited to examination of the brain only. Autopsies at DUMC are generally limited to the chest, abdomen and pelvis, and the limbs are typically not examined. VTE identified at autopsy, therefore, included PE and DVT involving the inferior vena cava and the abdominal, iliac, brachiocephalic, subclavian, and/or internal jugular veins. For Durham county patients with autopsy-proven VTE, we reviewed the medical records for the clinical characteristics of these individuals, including whether VTE was clinically suspected (or known) prior to death. To evaluate the total number of deaths in Durham county residents within the same time period, we obtained data from the Durham county Register of Deeds office and the NC Vital Records office. Results: During the two year study period, a total of 677 autopsies were performed at DUMC as shown in the figure below. Figure 1 Figure 1. Of the 97 autopsies on patients from Durham county, VTE was diagnosed at autopsy in 19 cases (19.6%). The mean age of patients diagnosed with VTE at autopsy was 54 years (range 21-82 years). Ten were male (53%). Characteristics of the events are summarized in the table below. Table 1Type of eventHospitalization at the time of death.Thromboprophylaxis prior to death.VTE diagnosed antemortemSubsegmental PE only (n=6) Segmental PE only (n=2) Both (n=4)5 2 33 2 21 0 0DVT* (n=6)531PE and DVT* (n=1)100Total (n=19)16102 * DVT involved the following veins: hepatic vein (2), left common iliac (1), internal jugular vein (1), inferior vena cava (1), “central” venous (1), and the mesenteric and pelvic veins (1) Slightly more than half the patients who were hospitalized at the time of death were receiving some type of thromboprophylaxis, and two of the patients had been diagnosed with VTE prior to their death. According to the pathologist’s report, PE was the direct cause of death in 4 cases. All patients had one or more risk factors for VTE as shown in table below. Table 2Predisposing FactorOccurrence, n (%)Hospitalization16 (84%)Age 〉4012 (63%)Surgery6 (32%)Obesity6 (32%)Cancer6 (32%)Diabetes mellitus5 (26%)Central venous catheter3 (16%)Prior known VTE1 (5%) One of the limitations of this analysis is the small number of autopsies that are currently performed in the US. During the two year period, a total of 3918 residents of Durham county died within the state of NC. The rate of autopsy for Durham County residents who died during the study period, therefore, was only 2.5% of all deaths during this period. Conclusions: The frequency of VTE identified at autopsy in our retrospective study is 19.6% (19 of 97). The majority of these patients were not suspected to have VTE prior to death. Although most were hospitalized, more than a third were not receiving thromboprophylaxis at the time of death. Hospitalization is a common risk factor for VTE, and VTE remains an important cause of death in hospitalized patients. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Venous thromboembolism (VTE), defined as deep vein thrombosis (DVT), pulmonary embolism (PE), or both, represents a major cause of morbidity and mortality in patients with cancer. VTE is the second leading cause of death in patients with cancer, after cancer itself, in the United States. Previous studies have suggested differences by race in the occurrence of VTE among cancer patients. The purpose of this study was to investigate clinical differences in black and white patients with VTE and cancer. Methods: We conducted an analysis of a CDC/Duke VTE surveillance project at the three hospitals in Durham County, North Carolina (Duke University Hospital, Duke Regional Hospital and the Durham VA Medical Center) from April 2012 through March 2014. A combination of electronic and manual review methods were used to identify unique Durham County residents with new diagnoses of objectively confirmed VTE. Data abstracted included demographics, risk factors including cancer, clinical data, treatment, and outcomes. Results: A total of 1028 patients with a new VTE were identified during the surveillance period. Twenty-seven patients who were not black or white (e.g., race not listed; Asian; etc), and 41 with VTE affecting areas other than PE or limb DVT (e.g., cerebral sinus venous thrombosis) were excluded from this analysis. Of the remaining 960 patients, slightly more than half were female (497/960=51.8%), more than half were black (508/960=52.9%), almost a third were obese (337/960 = 35.1%), and median age was 59 years old. At the time of their VTE diagnosis, 184 patients with VTE (19.2%) had active cancer, defined as metastatic or diagnosed within the previous 6 months. The proportion of VTE associated with cancer varied by race. Among the 508 black patients with VTE, 111 (21.9%) had active cancer; in comparison, among the 452 white patients with VTE, 73 (16.1%) had active cancer (p-value=0.025). Black patients with VTE and cancer were older, had a lower body mass index (BMI), and were less likely to have sustained a prior VTE compared to black patients with VTE who did not have cancer (Table 1). Similarly, white patients with VTE and cancer had a lower BMI than white patients without cancer (Table 1). However, in contrast to the findings for black patients, white patients with VTE and cancer were not significantly older and did not show differences in having a prior VTE than white patients with VTE who did not have cancer. Additionally, white patients with VTE and cancer were much more likely to have sustained a PE, with or without DVT, and less likely to have sustained a DVT alone, than white patients with VTE who did not have cancer (Table 1). Black and white patients with both VTE and cancer, were similar in several aspects; however, white patients were less likely to have sustained a DVT alone and more likely to have sustained a PE, with or without DVT, compared to black patients. The types of cancer most frequently encountered in black patients with VTE were gastrointestinal (24.3%), genitourinary (23.4%), and lung (18.9%), followed by breast (8.1%), gynecologic (9.0%) and hematologic malignancies (9.9%). The types of cancer most frequently encountered in white patients with VTE were lung (27.4%), breast (16.4%), and gastrointestinal (13.7%), followed by genitourinary (9.6%), gynecologic (8.2%) and hematologic malignancies (6.8%). Black and white patients with VTE and cancer were treated similarly to black and white patients with VTE who did not have cancer, with most receiving anticoagulant therapy and fewer than 10% receiving an IVC filter (Table 1). Enoxaparin was used most frequently, followed by warfarin. Conclusions: There are several notable demographic and clinical differences between patients with VTE with and without cancer. While differences were observed for both black and white patients, several factors that were variable according to cancer status were unique to either black patients or white patients. One notable difference between black and white patients with both VTE and cancer was a lower proportion of DVT only and a higher proportion of PE, with or without DVT, in white patients. Disclosures Ortel: Instrumentation Laboratories: Consultancy.

Description: Introduction: Venous thromboembolism (VTE), defined as deep vein thrombosis (DVT), pulmonary embolism (PE), or both, has been estimated to affect 300,000 to 600,000 individuals in the US each year. Incidence estimates suggest that African Americans have similar, or slightly higher, rates of VTE compared to Whites, while Asians appear to have a lower rate (Beckman, et al., Am J Prev Med, 2010;38:S495-S501). Acquired risk factors for VTE can be identified in ~50% of cases. Using a population-based approach, we used multiple case finding techniques to improve estimates of VTE occurrence in a geographically defined, racially diverse population. Methods: Durham County, NC, has a population of ~280,000 individuals, characterized as: 52.4% female; 53% White, 38.8% African American, 4.9% Asian, 1% American Indian, and 2.2% ≥2 races; and 13.5% Hispanic (US Census Data, 2012). The County is served by three hospitals, two in the Duke University Health System (DUHS) that share an electronic medical record, and the Durham Veterans’ Administration Medical Center (VAMC). We used a combination of methods to systematically identify patients living in Durham County with a new diagnosis of VTE. These included direct review of imaging data in the Duke Picture Archive and Communication System (PACS); automated review of ICD9 diagnosis codes for VTE and CPT codes for imaging procedures used for diagnosing DVT and PE stored in the Duke Medicine Enterprise Data Warehouse via the Duke Enterprise Data Unified Content Explorer (DEDUCE); direct review of Duke autopsy reports; and review of Veterans Health Information Systems and Technology Architecture (VISTA) to identify cases at the VAMC. Individual patients and events were cross-referenced to avoid duplicate entries, and demographic, risk factor, and treatment data were collected by record review and entered into a REDCap database. Data for the 9 month period from March through November 2013 collected at the DUHS hospitals are included in this abstract. Results: During the study period, we identified a total of 273 unique individuals with VTE, resulting in an estimated annual incidence of 1.3 per 1,000 individuals in Durham County. The mean age of the patients was 61.6 years (range, 19 to 99 years), and 153 (56%) were female. Mean BMI was 29.5±8.4. Racial distribution of VTE and estimated annual incidence is shown in the table below. Table 1RacePatients, n (%)Estimated annual incidence per 1,000 populationAsian2 (0.73%)0.19African American164 (60%)2.01White104 (38%)0.93Other3 (1.1%)0.45 Characteristics of some of the events and risk factors comparing African American and White patients are shown in the table below. Abstract 4256. Table 2Total (total n=273)African American (total n=164)White (total n=104)Pulmonary emboli141/271 (52%)91/163 (55.8%)48/103 (46.6%)History of prior VTE63/273 (23%)38/162 (23.2%)25/103 (24%)Surgery within the preceding 90 days103/238 (43%)55/151 (36.4%)34/92 (38.0%)Active cancer57/246 (23%)38/153 (24.8%)18/89 (20.2%)Catheter-related17/250 (7%)11/148 (7.4%)6/88 (6.8%) None of these comparisons were statistically significant. Three African American patients had sickle cell disease. Hypertension (p=0.0392) and end-stage renal disease (p=0.0038) occurred more frequently in African American VTE patients compared to White VTE patients. Most patients were treated with anticoagulant therapy at the time of diagnosis (n=236; 87%), including low-molecular weight heparin (n=167; 70.8%), unfractionated heparin (n=78; 33.1%), and rivaroxaban (n=21; 8.9%); some patients received more than 1 agent. 129 patients (54.7%) were started on warfarin at the time of diagnosis. A minority of patients were treated with thrombolytic therapy (n=7; 2.6%), thrombectomy/embolectomy (n=3; 1.1%), or placement of an IVC filter (n=19; 7%). Major bleeding occurred in 6 patients (2.2%). These estimates are subject to limitations. They do not include Durham County residents who were diagnosed and treated completely outside the county, and cases from the Durham VAMC are pending. Conclusions: Our VTE surveillance case finding approach resulted in an estimated annual VTE incidence of ~1.3 persons per 1,000 per year, with an incidence in African Americans that is approximately twice the incidence in Whites. Common risk factors were similar for African Americans and Whites, but hypertension and end-stage renal disease were more common comorbid conditions in African Americans. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 2982 Poster Board II-958 Pregnancy complications such as recurrent miscarriage, intrauterine growth restriction (IUGR), and preeclampsia are common and have been associated with thrombophilia. However racial differences are poorly described for this population. The objective of this study was to determine racial differences in unexplained adverse pregnancy outcome among women obtaining care in the CDC Thrombosis and Hemostasis Centers Research and Prevention Network. Uniform data were prospectively collected from August 2003 to March 2009 in consenting women with a history of adverse pregnancy outcome obtaining care at Network Centers for pre-pregnancy, pregnancy, or postpartum consultation and/or management. Data from 407 women (mean age 38.5 ±12 yrs), including 326 white women (mean age 39.4 ± 12 yrs), and 60 black women (mean age 33.9 ± 11 yrs) were analyzed. Black women had significantly more second trimester pregnancy losses compared to white women (35% vs 22%, p=0.03) but the proportions of 1st trimester losses, 3rd trimester losses, IUGR, prematurity, abruption, and preeclampsia were not significantly different. The risk of thrombophilia differed by race, with Factor V Leiden mutation more common in white women compared to black women (19% vs 3%, p=0.002). Protein S deficiency was more common in black women compared to white women overall (15% vs 5%, p=0.006) and in the subgroup of non-pregnant women (14% vs 5%, p=0.04). There was no significant difference in the proportion of white and black women with antiphospholipid antibodies. Among 285 women evaluated when non-pregnant, body mass index (BMI) ≥ 25 was more frequent in black women (83%) compared to white women (63%) (p=0.04). Overall, black women had a significantly higher proportion with hypertension (27% vs 11%, p=0.002) and sickle cell disease (7% vs 0,%, p〈 0.001). There was no significant racial difference in history of pregnancy associated, provoked, or idiopathic venous thromboembolism (VTE). A family history of thrombophilia (6% vs 0%, p=0.05), VTE (22% vs 7%, p=0.005), myocardial infarction (MI) or stroke (12% vs 0%, p=0.0042) was significantly more common in white women compared to black women (overall 32% vs 8%, p