Search

Background: Venous thromboembolism (VTE) stands as the leading cause of preventable death within hospitals in the United States. Although there have been some studies investigating the incidence rates of VTE, there has yet to be a large-scale study elucidating disparities in sex, race, income, region, and seasons in patients with VTE. The goal of this study was to report the disparities in race, sex, income, region, and seasons in patients with VTE, pulmonary embolism (PE), and deep vein thrombosis (DVT), in hospitalized patients from 2016 to 2019., Methods: We used the United States National Inpatients Sample database to identify inpatients diagnosed with PE, DVT, and PE and DVT from 2016 to 2019. The inpatient incidence per thousand was calculated for sex and race using the weighted sample model. The regional and monthly incidence of DVT and PE per thousand inpatients and risk of incidence were calculated. Patients' characteristics including hospital type, bed size, median length of stay, median total charges, and mortality were also collected., Results: We examined 455,111 cases of VTE, 177,410 cases of DVT, 189,271 cases of PE, and 88,430 cases of both DVT and PE combined. Over the study period, we observed a statistically significant trend among PE hospitalization incidences. There was a strong and positive correlation between DVT and PE inpatients. Black inpatients had the highest cumulative incidence of hospitalizations in all cohorts with 10.36 per 1000 in PE and 9.1 per 1000 in DVT. Asian and Pacific Islander inpatients had the lowest cumulative incidence with 4.42 per 1000 in PE and 4.28 per 1000 in DVT. Females showed the lowest cumulative incidence with 7.47 per 1000 in PE and 6.53 per 1000 in DVT. The Mountain region was the highest among PE hospitalizations with 9.62 per 1000. For DVT, the Middle Atlantic region was the highest at 8.65 per 1000. The in-hospital mortality rate was the highest among the PE hospitalizations at 7.3%. Also, the trend analysis showed significant increases among all groups., Conclusions: Over the study period (2016-2019), we report the racial, biological sex, and geographical disparities from the National Inpatient Sample database, highlighting that Black inpatients had the highest incidence of PE and DVT, whereas Asian/Pacific Islander inpatients had the lowest incidences of PE and DVT. Moreover, women had a lower incidence compared with men. The observed regional variations indicated that the incidence of PE was highest in the Mountain region, whereas the incidence of DVT was lowest in the Middle Atlantic region. There was an increase in the mortality of inpatients diagnosed with VTE reflecting the growing burden of this condition in the US health care system., Competing Interests: Disclosures None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Importance: COVID-19 has disproportionately affected racialized populations, with particular impact among individuals of Black individuals. However, it is unclear whether disparities in venous thromboembolic (VTE) complications exist between Black individuals and those belonging to other racial groups with confirmed SARS-CoV2 infections., Objective: To summarize the prevalence and moderators associated with VTE among Black COVID-19 patients in minoritized settings, and to compare this to White and Asian COVID-19 patients according to sex, age, and comorbid health conditions (heart failure, cancer, obesity, hypertension)., Design Setting, and Participants: A systematic search of MEDLINE, Embase, CINAHL and CENTRAL for articles or reports published from inception to February 15, 2023., Study Selection: Reports on VTE among Black individuals infected with SARS-CoV2, in countries where Black people are considered a minority population group., Data Extraction and Synthesis: Study characteristics and results of eligible studies were independently extracted by 2 pairs of reviewers. VTE prevalence was extracted, and risk of bias was assessed. Prevalence estimates of VTE prevalence among Black individuals with COVID19 in each study were pooled. Where studies provided race-stratified VTE prevalence among COVID19 patients, odds ratios were generated using a random-effects model., Main Outcomes and Measures: Prevalence of VTE, comprising of deep vein thrombosis and pulmonary embolism., Results: Ten studies with 66,185 Black individuals reporting the prevalence of COVID-19 associated VTE were included. Weighted median age of included studies was 47.60. Pooled prevalence of COVID-19 associated VTE was 7.2 % (95 % CI, 3.8 % - 11.5 %) among Black individuals. Among individuals with SARS-CoV2 infections, Black population had higher risks of VTE compared to their White (OR = 1.79, [95 % CI 1.28-2.53], p < .001) or Asian (OR = 2.01, [95 % CI, 1.14-3.60], p = .017) counterparts, or patients with other racial identities (OR = 2.01, [95 % CI, 1.39, 2.92]; p < .001)., Conclusions and Relevance: Black individuals with COVID-19 had substantially higher risk of VTE compared to White or Asian individuals. Given racial disparities in thrombotic disease burden related to COVID-19, medical education, research, and health policy interventions are direly needed to ensure adequate disease awareness among Black individuals, to facilitate appropriate diagnosis and treatment among Black patients with suspected and confirmed VTE, and to advocate for culturally safe VTE prevention strategies, including pre-existing inequalities to the COVID-19 pandemic that persist after the crisis., Competing Interests: Declaration of competing interest No conflict of interest for any author., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Racial disparities in aortic valve replacement outcomes have been established. However, the current literature lacks comprehensive studies that examine the outcomes for Native Americans, probably due to their limited population size. This study aimed to investigate whether disparities in transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) also exist for outcomes among Native Americans., Methods: Patients who underwent SAVR and TAVR were identified in National Inpatient Sample from the last quarter of 2015 to 2020. A 1:5 propensity score matching was conducted between Native Americans and Caucasians. In-hospital perioperative outcomes, length of stay, wait from admission to operation, and total hospital charge, were compared., Results: In TAVR, 51,394 (84.41 %) were Caucasians and 171 (0.28 %) were Native Americans. In SAVR, there were 50,080 (78.52 %) Caucasians and 279 (0.44 %) Native Americans. After propensity matching, no significant difference was found in post-TAVR outcomes between Native Americans and Caucasians. However, Native Americans have a higher risk of neurological complications (2.88 % vs 0.79 %, p < 0.01) with stroke being the primary contributor (2.52 % vs 0.5 %, p < 0.01), as well as a higher incidence of venous thromboembolism (1.8 % vs 0.57 %, p < 0.05) after SAVR., Conclusions: This study is the first to examine aortic valve replacement outcomes in Native Americans. Native Americans were found to be more likely to undergo SAVR than TAVR. Moreover, Native Americans were found to have five times higher stroke and three times higher VTE after SAVR. These disparities faced by Native Americans underscore the need for increased attention and targeted actions to guarantee health equity., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Whether prevention strategy for postoperative venous thromboembolism (VTE) should be tailored across racial groups remains unknown., Methods: Patients who underwent major abdominal operation in the Nationwide Inpatient Sample (NIS) were examined. Our primary outcome was postoperative VTE, and the secondary outcome was postoperative bleeding. Multivariable logistic regression analyses were performed and validated with the National Surgical Quality Improvement Program (NSQIP) database., Results: 781,888 patients from NIS were analyzed. Overall VTE rate was 2.0%. Compared to White patients, Hispanic (OR 0.85, 95% CI 0.78-0.93, p < 0.01) and Asian patients (OR 0.49, 95% CI 0.40-0.61, p < 0.01) had significantly lower risks for VTE. In contrast, Asian patients had a significantly higher risk of bleeding (OR 1.39, 95% CI 1.24-1.56, p < 0.01). Similar trends were observed in NSQIP., Conclusions: The risk-benefit ratio of postoperative VTE prophylaxis for Asian patients is roughly three times higher than that for White patients, suggesting a tailored approach is necessary., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Limited existing data suggest that the novel COVID-19 may increase risk of VTE, but information from large, ethnically diverse populations with appropriate control participants is lacking., Research Question: Does the rate of VTE among adults hospitalized with COVID-19 differ from matched hospitalized control participants without COVID-19?, Study Design and Methods: We conducted a retrospective study among hospitalized adults with laboratory-confirmed COVID-19 and hospitalized adults without evidence of COVID-19 matched for age, sex, race or ethnicity, acute illness severity, and month of hospitalization between January 2020 and August 2020 from two integrated health care delivery systems with 36 hospitals. Outcomes included VTE (DVT or pulmonary embolism ascertained using diagnosis codes combined with validated natural language processing algorithms applied to electronic health records) and death resulting from any cause at 30 days. Fine and Gray hazards regression was performed to evaluate the association of COVID-19 with VTE after accounting for competing risk of death and residual differences between groups, as well as to identify predictors of VTE in patients with COVID-19., Results: We identified 6,319 adults with COVID-19 and 6,319 matched adults without COVID-19, with mean ± SD age of 60.0 ± 17.2 years, 46% women, 53.1% Hispanic, 14.6% Asian/Pacific Islander, and 10.3% Black. During 30-day follow-up, 313 validated cases of VTE (160 COVID-19, 153 control participants) and 1,172 deaths (817 in patients with COVID-19, 355 in control participants) occurred. Adults with COVID-19 showed a more than threefold adjusted risk of VTE (adjusted hazard ratio, 3.48; 95% CI, 2.03-5.98) compared with matched control participants. Predictors of VTE in patients with COVID-19 included age ≥ 55 years, Black race, prior VTE, diagnosed sepsis, prior moderate or severe liver disease, BMI ≥ 40 kg/m 2 , and platelet count > 217 k/μL., Interpretation: Among ethnically diverse hospitalized adults, COVID-19 infection increased the risk of VTE, and selected patient characteristics were associated with higher thromboembolic risk in the setting of COVID-19., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background:  Contemporary incidence data for venous thromboembolism (VTE) from racially diverse populations are limited. The racial distribution of Oklahoma County closely mirrors that of the United States., Objective:  To evaluate VTE incidence and mortality, including demographic and racial subgroups., Design:  Population-based prospective study., Setting:  We conducted VTE surveillance at all relevant tertiary care facilities and outpatient clinics in Oklahoma County, Oklahoma during 2012 to 2014, using both active and passive methods. Active surveillance involved reviewing all imaging reports used to diagnose VTE. Passive surveillance entailed identifying VTE events from hospital discharge data and death certificate records., Measurements:  We used Poisson regression to calculate crude, age-stratified, and age-adjusted incidence and mortality rates per 1,000 population per year and 95% confidence intervals (CIs)., Results:  The incidence rate of all VTE was 3.02 (2.92-3.12) for those age ≥18 years and 0.05 (0.04-0.08) for those <18 years. The age-adjusted incidence rates of all VTE, deep vein thrombosis, and pulmonary embolism were 2.47 (95% CI: 2.39-2.55), 1.47 (1.41-1.54), and 0.99 (0.93-1.04), respectively. The age-adjusted VTE incidence and the 30-day mortality rates, respectively, were 0.63 and 0.121 for Asians/Pacific Islanders, 3.25 and 0.355 for blacks, 0.67 and 0.111 for Hispanics, 1.25 and 0.195 for Native Americans, and 2.71 and 0.396 for whites., Conclusion:  The age-adjusted VTE incidence and mortality rates vary substantially by race. The incidence of three per 1,000 adults per year indicates an important disease burden, and is informative of the burden in the U.S., Competing Interests: G.E.R. discloses the receipt of consultant fees for consultant services provided to the following companies: Anthos, Bayer, BMS, Boehringer-Ingelheim, Daiichi-Sankyo, Eli Lilly, Janssen, Johnson and Johnson, Merck, Pfizer, Portola, Tetherex, and XaTek. G.E.R. and A.M.W. were recipients of research grants from the CDC. The other authors report no conflicts to disclose., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background : Venous thromboembolism (VTE) occurs frequently in acute myeloid leukemia (AML) patients. There are no population-based studies from the United States (U.S.) analyzing this association. The study aims to analyze the trends, predictors of mortality, and outcomes of VTE in AML patients. Methods : We analyzed the publicly available Nationwide Inpatient Sample (NIS) for years 2010-2014. Hospitalizations due to AML were identified by previously validated International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes as the primary diagnosis. VTE was identified by ICD-9-CM codes as secondary diagnosis. Hospitalizations with age less than 18 years of age were excluded. The trends and outcomes were determined using Chi-squared (χ2) test and multivariate regression models. Results : From 2010 to 2014, there were 313,282 hospitalizations with a primary diagnosis of AML and 1,633 hospitalizations (0.1%) had VTE as a concurrent diagnosis. There was a significant increase in the proportion of AML hospitalizations with VTE from 0.47% in 2010 to 0.56% in 2014 (P = 0.014). Multivariable regression analysis showed that the odds of in-hospital mortality were not higher in AML hospitalizations with VTE (odds ratio [OR] 1.11; 95% confidence interval [CI] 0.81-1.52; P = 0.5) than those without VTE. Age group above 84 years carried the highest risk of mortality (OR 3.20; 95% CI 2.77-3.70; P < 0.0001) in AML-VTE patients. Black (OR 1.23; 95% CI 1.13-1.35; P < 0.0001) and uninsured patients (OR 1.50; 95% CI 1.31-1.73; P < 0.0001) were at significantly higher odds of in-hospital mortality amongst the AML-VTE hospitalizations. Conclusion : The proportion of AML hospitalizations with VTE continues to rise in the U.S. After adjusting for confounders, increasing age, Black race, and lack of insurance were found to have higher risk of in-hospital mortality in the AML-VTE cohort. The odds of in-hospital mortality in AML hospitalizations with VTE are not higher than those without VTE.

This study aimed to compare the predictive value of 2009 and 2013 version of Caprini risk assessment models (RAM) for venous thromboembolism (VTE) in cancer patients by receiver operating characteristic (ROC) analysis. This retrospective study reviewed a total of 1439 VTE and 1439 non-VTE Chinese cancer inpatients. The baseline demographic data of these patients were recorded. 2009 and 2013 versions Caprini RAMs were applied, and cumulative risk scores were obtained by adding the scores of each risk factor. The specificity, sensitivity, positive predictive value and negative predictive value of these two models were analyzed. ROC curve was drawn to calculate the area under the curve (AUC) and the Youden index. Significant differences were observed in the risk factors between VTE and non-VTE Group. The specificity and negative predictive value of 2013 version were higher than those of 2009 version (P < 0.05). No significant differences were found in the sensitivity or positive predictive value between 2009 and 2013 versions of the Caprini RAM (P > 0.05). The AUC and Youden index of 2013 Caprini RAM were significantly higher than those of 2009 Caprini RAM (P < 0.001), whereas the Youden index of the 2009 Caprini RAM at critical point 4 was higher than that at critical point 3 (0.362 vs 0.067, P < 0.05). Compared with 2009 version, 2013 version of the Caprini RAM provides a more accurate and efficacious method for the risk assessment of VTE in Chinese cancer patients.

Objectives: Prevalence and trends in all cardiovascular disease (CVD) risk factors among young adults (18-39 years) have not been evaluated on a large scale stratified by sex and race. The aim of this study was to establish the prevalence and temporal trend of CVD risk factors in US inpatients younger than 40 years of age from 2007 through 2014 with racial and sex-based distinctions. In addition, the impact of these risk factors on inpatient outcomes and healthcare resource utilization was explored., Methods: A cross-sectional nationwide analysis of all hospitalizations, comorbidities, and complications among young adults from 2007 to 2014 was performed. The primary outcomes were frequency, trends, and race- and sex-based differences in coexisting CVD risk factors. Coprimary outcomes were trends in all-cause mortality, acute myocardial infarction, arrhythmia, stroke, and venous thromboembolism in young adults with CVD risk factors. Secondary outcomes were demographics and resource utilization in young adults with versus without CVD risk factors., Results: Of 63 million hospitalizations (mean 30.5 [standard deviation 5.9] years), 27% had at least one coexisting CVD risk factor. From 2007 to 2014, admission frequency with CVD risk factors increased from 42.8% to 55.1% in males and from 16.2% to 24.6% in females. Admissions with CVD risk were higher in male (41.4% vs 15.9%) and white (58.4% vs 53.8%) or African American (22.6% vs 15.9%) patients compared with those without CVD risk. Young adults in the Midwest (23.9% vs 21.1%) and South (40.8% vs 37.9%) documented comparatively higher hospitalizations rates with CVD risk. Young adults with CVD risk had higher all-cause in-hospital mortality (0.4% vs. 0.3%) with a higher average length of stay (4.3 vs 3.2 days) and charges per admission ($30,074 vs $20,124)., Conclusions: Despite modern advances in screening, management, and interventional measures for CVD, rising trends in CVD risk factors across all sex and race/ethnic groups call for attention by preventive cardiologists.

Objective: Venous thromboembolism (VTE) is associated with significant morbidity and mortality. Resting heart rate (RHR), which may be modifiable through lifestyle changes, has been shown to be associated with cardiovascular disease risk and with inflammatory markers that have been predictive of VTE incidence., Methods: We examined whether RHR is also associated with VTE incidence independent of these risk factors. We studied 6479 Multi-Ethnic Study of Atherosclerosis participants free from clinical VTE at baseline who had baseline RHR ascertained by 12-lead ECG. VTE events were recorded from hospital records and death certificates using International Classification of Diseases (ICD)-9 and ICD-10 codes. We categorised RHR as <60, 60-69, 70-79 and ≥80 bpm. We used Cox hazard models to determine the association of incident VTE by RHR., Results: Participants had mean (SD) age of 62 (10) years and RHR of 63 (10) bpm. RHR was cross-sectionally correlated with multiple inflammatory and coagulation factors. There were 236 VTE cases after a median follow-up of 14 years. Compared with those with RHR<60 bpm, the HR (95% CI) for incident VTE for RHR≥80 bpm was 2.08 (1.31 to 3.30), after adjusting for demographics, physical activity, smoking, diabetes and use of atrioventricular (AV)-nodal blockers, aspirin and anticoagulants, and remained significant after further adjustment for inflammatory markers (2.05 (1.29 to 3.26)). Results were similar after excluding those taking AV-nodal blocker medications. There was no effect modification of these associations by sex or age., Conclusion: Elevated RHR was positively associated with VTE incidence after a median of 14 years; this association was independent of several traditional VTE and inflammatory markers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Purpose: Cancer patients are at a higher risk of venous thromboembolism (VTE) than the general population. In the general population, blacks are at a higher risk of VTE compared with whites. The influence of race on cancer-associated VTE remains unexplored. We examined whether black cancer patients are at a higher risk of VTE and whether these differences are present in specific cancer types., Design: A retrospective study was performed in the largest safety net hospital of New England using a cohort of cancer patients characterized by a substantial number of nonwhites., Results: We identified 16,498 subjects with solid organ and hematologic malignancies from 2004 to 2018. Among them, we found 186 unique incident VTE events, of which the majority of the events accrued within the first 2 years of cancer diagnosis. Overall, blacks showed a 3-fold higher incidence of VTE (1.8%) compared with whites (0.6%; P<0.001). This difference was observed in certain cancer types such as lung, gastric and colorectal. In lung cancer, the odds of developing VTE in blacks was 2.77-times greater than those in white patients (confidence interval, 1.33-5.91; P=0.007). Despite the greater incidence of cancer-associated VTE in blacks, their Khorana risk score of VTE was not higher., Conclusions: In a diverse cancer cohort, we observed a higher incidence of cancer-associated VTE in blacks compared with patients from other races. This study indicates the consideration of race in the risk assessment of cancer-associated VTE. It could also lead to future mechanistic studies aiming at identifying reasons for differential VTE risk depending on cancer type.

Severe acute respiratory syndrome coronavirus 2 infection (COVID-19) is known to induce severe inflammation and activation of the coagulation system, resulting in a prothrombotic state. Although inflammatory conditions and organ-specific diseases have been shown to be strong determinants of morbidity and mortality in patients with COVID-19, it is unclear whether preexisting differences in coagulation impact the severity of COVID-19. African Americans have higher rates of COVID-19 infection and disease-related morbidity and mortality. Moreover, African Americans are known to be at a higher risk for thrombotic events due to both biological and socioeconomic factors. In this review, we explore whether differences in baseline coagulation status and medical management of coagulation play an important role in COVID-19 disease severity and contribute to racial disparity trends within COVID-19.

Background: Venous thromboembolism (VTE) is a multifactorial disease in which genetic and acquired risk factors may contribute to disease pathogenesis. Several studies have demonstrated that β-fibrinogen (FGB) polymorphisms are associated with the risk of VTE. However, the results of these studies were not totally consistent. In this paper, we performed a meta-analysis to further investigate the relationship between FGB polymorphisms and susceptibility to VTE., Methods: To identify studies pertinent to the focused question, the following databases were systematically searched: PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, and Wanfang Data. The strength of correlations was evaluated by calculating pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). Subgroup analyses stratified by ethnicity, type of disorders, and source of control were also performed., Results: Overall, A total of 18 relevant case-control studies met the inclusion criteria and were incorporated in this meta-analysis, involving 3033 VTE cases and 4547 healthy controls. FGB -455G>A polymorphism and -148C>T polymorphism were not significantly associated with susceptibility to VTE in overall populations. However, results of stratified analysis demonstrated that among Caucasian population, the -455G>A mutation was negatively associated with the risk of VTE under all genetic comparison models (A:G OR = 0.80 95% CI = 0.70-0.91; GA + AA:GG OR = 0.80 95% CI = 0.68-0.93; GA:GG OR = 0.84 95% CI = 0.71-0.98; AA:GG + GA OR = 0.61 95% CI = 0.43-0.87; AA:GG OR = 0.57 95% CI = 0.40-0.82), which indicates FGB -455G>A polymorphism may be a protective factor for VTE. There was no correlation between -148C>T polymorphism and susceptibility to VTE in all subgroup analyses., Conclusion: FGB -455G>A polymorphism was associated with a decreased risk of VTE among the Caucasian population.

Venous thromboembolism (VTE) is a common hematological disorder. VTE affects millions of people around the world each year and can be fatal. Earlier studies have revealed the possible VTE genetic risk factors in Europeans. The 2018 Critical Assessment of Genome Interpretation (CAGI) challenge had asked participants to distinguish between 66 VTE and 37 non-VTE African American (AA) individuals based on their exome sequencing data. We used variants from AA VTE association studies and VTE genes from DisGeNET database to evaluate VTE risk via four different approaches; two of these methods were most successful at the task. Our best performing method represented each exome as a vector of predicted functional effect scores of variants within the known genes. These exome vectors were then clustered with k-means. This approach achieved 70.8% precision and 69.7% recall in identifying VTE patients. Our second-best ranked method had collapsed the variant effect scores into gene-level function changes, using the same vector clustering approach for patient/control identification. These results show predictability of VTE risk in AA population and highlight the importance of variant-driven gene functional changes in judging disease status. Of course, more in-depth understanding of AA VTE pathogenicity is still needed for more precise predictions., (© 2019 Wiley Periodicals, Inc.)

Although recent Genome-Wide Association Studies have identified novel associations for common variants, there has been no comprehensive exome-wide search for low-frequency variants that affect the risk of venous thromboembolism (VTE). We conducted a meta-analysis of 11 studies comprising 8,332 cases and 16,087 controls of European ancestry and 382 cases and 1,476 controls of African American ancestry genotyped with the Illumina HumanExome BeadChip. We used the seqMeta package in R to conduct single variant and gene-based rare variant tests. In the single variant analysis, we limited our analysis to the 64,794 variants with at least 40 minor alleles across studies (minor allele frequency [MAF] ~0.08%). We confirmed associations with previously identified VTE loci, including ABO, F5, F11, and FGA. After adjusting for multiple testing, we observed no novel significant findings in single variant or gene-based analysis. Given our sample size, we had greater than 80% power to detect minimum odds ratios greater than 1.5 and 1.8 for a single variant with MAF of 0.01 and 0.005, respectively. Larger studies and sequence data may be needed to identify novel low-frequency and rare variants associated with VTE risk., (© 2019 Wiley Periodicals, Inc.)

Essentials Ceruloplasmin (CP) is an acute-phase reactant and a potential biomarker of atherothrombotic risk. We assessed associations between CP and venous thromboembolism (VTE) risk in 9933 individuals. Higher circulating CP but not CP-related genes were associated with greater incident VTE rates. Circulating CP could be considered a non-causal biomarker of VTE risk in the community. SUMMARY: Background Ceruloplasmin (CP) is an acute-phase reactant and a potential biomarker of atherothrombotic risk. We assessed the associations between CP, CP-associated genetic variants and incident venous thomboembolism (VTE) in the Atherosclerosis Risk in Communities study. Methods and results In an observational study, 9933 men and women aged 53-75 years without prevalent VTE were included in 1996-1998 and followed through 2011. Circulating CP was measured in stored blood samples obtained in 1996-1998. Polymorphisms rs11708215 and rs13072552, which have been previously associated with CP concentrations, were measured in 8439 participants. VTEs were identified from hospital discharge codes and validated by physician review of medical records and imaging reports. Over a mean of 10.5 years of follow-up, 376 cases of VTE were identified. The association between circulating CP, CP-associated polymorphisms and the incidence of VTE was estimated. After adjustment for traditional risk factors and biomarkers, higher concentrations of circulating CP were associated with greater incident VTE rates (hazard ratio 1.82, 95% confidence interval 1.12-2.95, comparing the 87.5-100th percentile with the bottom quartile). Both rs11708215 and rs13072552 were associated with CP concentrations but not with VTE risk. Conclusions Even though high CP concentrations were associated with an increased VTE risk, CP-associated genetic variants were not associated with a higher risk of VTE. Our results suggest that circulating CP concentrations may not be causally related to the risk of incident VTE., (© 2019 International Society on Thrombosis and Haemostasis.)

Background: Beginning in 2012, direct oral anticoagulants (DOACs) were approved for treatment and prevention of venous thromboembolism. Prior investigations have demonstrated slow rates of adoption of novel therapeutics for black patients. We assessed the association of racial/ethnic and socioeconomic factors with DOAC use among commercially insured venous thromboembolism patients., Methods and Results: We performed a retrospective cohort analysis of adult patients with an incident diagnosis of venous thromboembolism between January 2010 and December 2016 using OptumInsight's Clinformatics Data Mart. We identified the first filled oral anticoagulant prescription within 30 days of discharge of an inpatient admission. We performed a multivariable logistic regression, adjusting for age, sex, race/ethnicity, region, zip code-linked household income, and clinical covariates to identify factors associated with the use of DOACs. Race and ethnicity were determined in this database through a combination of public records, self-report, and proprietary ethnicity code tables. There were 14 140 patients included in the analysis. Treatment with DOACs increased from <0.1% in 2010 to 65.6% in 2016. In multivariable analyses, black patients were less likely to receive a DOAC compared with white patients (odds ratio, 0.86; 95% CI, 0.77-0.97; P=0.02). There were no differences in DOAC utilization among Asian (odds ratio, 1.06; 95% CI, 0.75-1.49; P=0.74) or Hispanic patients (odds ratio, 1.04; 95% CI, 0.88-1.22; P=0.66) compared with whites. Patients with a household income over $100 000 per year were more likely to receive DOAC therapy compared with patients with a household income of <$40 000 per year (odds ratio, 1.50; 95% CI, 1.33-1.69; P<0.0001)., Conclusions: Although DOAC adoption has increased steadily since 2012, among a commercially insured population, black race and low household income were associated with lower use of DOACs for incident venous thromboembolism despite controlling for other clinical and socioeconomic factors. These findings suggest the possibility of both racial and socioeconomic inequity in access to this novel pharmacotherapy.

Protein S (PS) deficiency is associated with a 10-fold increased risk of venous thromboembolism (VTE), but its diagnosis is quite difficult and complicated. In this study, we identified 53 unrelated pedigrees with PS deficiency in China. Data of their clinical characteristics and laboratory examinations were collected. Genetic analysis of PROS1 including direct sequencing, copy number variant detection and messenger ribonucleic acid analysis was performed in probands and related family members. Of these 53 probands, 52.8% (28/53) experienced multi-site and/or recurrent thrombotic episodes, mainly manifested as deep venous thrombosis and/or pulmonary embolism (82.7%). Additional risk factors of VTE were observed in 39.6% (21/53) probands who exhibited a significantly higher rate of recurrent VTE compared with those not, in which 7 probands were complicated by anti-phospholipid syndrome. Most probands and family members exhibited quantitative PS deficiency with impairment of both activated protein C and tissue factor pathway inhibitor cofactor activities. Note that 87.2% (34/39) PROS1 detectable mutation rate was obtained through comprehensive phenotypic and genetic analysis. A total of 36 PROS1 causative mutations including 16 novel mutations were identified in 48 probands, whereas no PROS1 mutations were detected in the other 5 probands. Three hotspot mutations (Glu67Ala, Arg561Trp and Tyr560*) were identified in the Chinese population for the first time. This article provides a framework for correlating the clinical pathogenesis of PS deficiency to genetic backgrounds in the Chinese population., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Despite much progress in microRNA (miRNA) research, information regarding the association between miRNAs and venous thromboembolism (VTE), especially in Asian patients, remains limited. This case-control study sought to determine the correlation between the presence of polymorphisms in the genes encoding the miRNAs miR-146a, miR-149, miR-196a2, miR-499, and VTE in Korean patients. We observed no statistically significant differences in the genotype frequency of miRNA polymorphisms between 300 control individuals and 203 VTE patients. However, we observed a significant association between three allelic combinations of miRNA polymorphisms and VTE risk. Overall, our findings suggest that specific miRNA polymorphisms are associated with the risk of VTE in a Korean population.

We performed this meta-analysis to better assess the relationship between methylenetetrahydrofolate reductase gene ( MTHFR) polymorphisms and the risk of venous thromboembolism. Eligible studies were searched in PubMed, Medline, Embase, and Web of Science. Odds ratios with 95% confidence intervals were used to assess associations of MTHFR polymorphisms with venous thromboembolism. A total of 99 genetic association studies were enrolled for analyses. Although no positive results were detected in overall analyses for the rs1801131 polymorphism. Further subgroup analyses according to ethnicity of participants and type of disease revealed that the rs1801131 polymorphism was significantly correlated with the risk of pulmonary embolism. For the rs1801133 polymorphism, significant association with the risk of venous thromboembolism was found in the dominant, recessive, and allele models. Further subgroup analyses according to ethnicity of participants revealed that the rs1801133 polymorphism was significantly associated with the risk of venous thromboembolism in Caucasians, East Asians, and West Asians. When we stratified available data according to type of disease, we found that the rs1801133 polymorphism was also significantly correlated with the risk of deep vein thrombosis and pulmonary embolism. In conclusion, our findings indicate that the MTHFR rs1801133 polymorphism may serve as a potential biological marker for venous thromboembolism in Caucasians, East Asians, and West Asians. Moreover, the MTHFR rs1801133 polymorphism may be implicated in the development of deep vein thrombosis and pulmonary embolism, while the MTHFR rs1801131 polymorphism may contribute to the development of pulmonary embolism.

Background: Venous thromboembolism (VTE) (deep venous thrombosis and pulmonary embolism) is a known complication following total knee arthroplasty (TKA). Recent literature has identified differences in VTE risk based on race with African Americans having higher risk of VTE. This study evaluated the impact of race on VTE following TKA using a large multicenter database., Methods: We queried the American College of Surgeons National Surgical Quality Improvement Program to identify patients who underwent primary TKA in 2010-2014. Patients were stratified based on race: Asian, Black/African American, White, and Other. Demographics were compared to determine the impact on 30-day postoperative complications. Multivariate logistic regression analysis was performed to control for confounding demographics and comorbidities between races. Primary outcomes included overall complications and VTE., Results: In total, 96,230 patients were included. Univariate analysis demonstrated that Blacks had a significantly higher rate of any complication (5.5%), deep venous thrombosis (1.3%), and pulmonary embolism (1.1%) than other races (P = .007, P < .001, and P < .001, respectively). Overall mortality rate did not differ between races (P = .26). Multivariate regression analysis identified that Blacks were significantly more likely to have a VTE than Whites (odds ratio 1.7, 95% confidence interval 1.4-2.0). Overall complications were significantly higher for Blacks than Whites (odds ratio 1.1, 95% confidence interval 1.02-1.3). There were no differences in the rates of VTE or overall complications between Asians/Other races and Whites., Conclusion: Blacks have a significantly higher risk of VTE following primary TKA than other races. Future studies should investigate causes for this disparity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aims: Dysfunctional prothrombin residue Arg596 associated mutation has been found to precipitate venous thromboembolism (VTE). In the current study we investigated the prevalence of Arg596 associated mutations in Chinese patients with VTE and explored the functional impact of Arg596Gln mutation on coagulation function in affected patients., Methods: Prothrombin clotting activity was measured in 267 unrelated patients with unprovoked VTE. Patients with moderately decreased activities underwent further analysis of the F2 gene. Prothrombin amidolytic activity and antigen levels were detected in mutation carriers. Specific family members were investigated about their VTE histories and clinical phenotypes. The thrombin generation test (TGT) was used to evaluate thrombin function and antithrombin resistance assay was applied to assess the extent of impaired antithrombin inhibition of mutation carriers., Results: Two heterozygous mutation carriers of prothrombin Arg596Gln were identified, both of whom had moderately decreased clotting activities but normal amidolytic activities and antigen levels. Among the families of the two probands, nine out of 13 mutation carriers experienced episodes of VTE. TGTs showed that patients had elevated endogenous thrombin potential and prolonged start tail time. Thrombin generation could be inhibited in the presence of thrombomodulin. The thrombin Arg596Gln variant in patients' plasma presented strong resistance to antithrombin inhibition., Conclusion: Prothrombin Arg596Gln mutation is a risk factor for Chinese patients with VTE due to its moderately decreased clotting activity but strong resistance to antithrombin inhibition. Prothrombin clotting activity screening and its encoding gene sequencing should be considered in patients with VTE when other established risk factors are absent., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Although rare in children, pulmonary embolism (PE) can cause significant morbidity and mortality. Overall rates of venous thromboembolism (VTE) are increasing in hospitalized children. By using the Pediatric Health Information System database, we evaluated incidence, treatment, and outcome of PE in children younger than age 18 years from 2001 to 2014. Demographic characteristics for those admitted with VTE alone and those admitted with PE were compared. Rates of PE by year were compared with the number of hospital and VTE admissions. Trends in medication use were analyzed. Over the period of the study, patients with PE made up 15.8% of VTE discharges. The overall rate of PE increased 200% ( P < .001). Compared with all other age groups, adolescents (age 13-18 years) had the highest prevalence (55%; P < .001), the rate of which increased from 9.8 to 24.7 per 10 000 hospital discharges (152%; P < .001), and from 17.5 to 34.1 per 100 VTE discharges (95%; P < .001). Individuals with PE had a higher mortality (8.3% vs 6%; P < .001) and were less likely to have a complex chronic condition (58% vs 65%; P < .001) than those with VTE alone. However, PE mortality rates decreased over the time period studied. African American and Hispanic patients were more likely to experience recurrent PE than white patients (12% and 10.7% vs 8%; P = .002). During the study period, the use of unfractionated heparin decreased ( P < .001), and the use of low molecular weight heparin increased ( P < .001). Further research is required to determine what factors contribute to the higher rate of PE in adolescents and influence recurrence in African American and Hispanic patients., (© 2018 by The American Society of Hematology.)

Introduction: Current epidemiological data for venous thromboembolism (VTE) are derived primarily from Caucasian populations from North America. Little is known for other ethnic groups. This study aimed to describe the incidence, etiologies, and the secular trends of VTE in a Chinese population., Materials and Methods: This was an observational study using a hospital VTE registry., Results and Conclusions: Between 2004 and 2016, 2214 patients (mean age 66.2 ± 17.4 years, 57.2% female) were hospitalized for a novel occurrence of venous thromboembolism. Of these, 1444 patients (65.2%) had deep venous thrombosis and 770 patients (34.8%) had pulmonary embolism. Over the 13-year period, there was an increasing trend in the incidence of VTE from 28.1 per 100,000 population per year in 2004 to 48.3 per 100,000 population per year in 2016. There has been a disproportional increase in the incidence of VTE among those aged 75 years or above. Etiologically, the most common cause of VTE was active malignancy with an incidence that increased from 34.8% in 2005 to 60.9% in 2014. In conclusion, the incidence of venous thromboembolism in Hong Kong appears to be lower than that in previous Caucasian series. Nonetheless there has been an increasing incidence of VTE over the past decade, primarily related to aging and malignancy., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aim: The genetic variants of the factor V (G1691A), prothrombin (G20210A) and MTHFR (C677T) genes have been widely implicated as inherited risk factors for developing venous thrombosis. This study was undertaken to reveal the frequency of these mutations in Kashmiri patients with venous thromboembolism., Methodology: A case-control study was designed with 250 VTE patients and 250 healthy controls. The mutations were analysed using ARMS-PCR and PCR-RFLP approach., Result: The factor V Leiden G1691A mutation was found in 17/250 (6.8%) VTE patients and prothrombin G20210A mutation was found in 7/250 (2.8%) VTE patients while no mutation was found in any of the healthy controls. Both the mutations were found to be significantly associated with the increased risk of VTE (p = 0.0001 and 0.0150 respectively) while no association of VTE risk with MTHFR C677T polymorphism was found (p = 0.53)., Conclusion: The increased frequency of factor V Leiden G1691A and prothrombin G20210A mutation in VTE patients indicates a significant role of these mutations in the development of VTE in our population. We therefore suggest the routine screening of these two mutations as thrombophilic markers in Kashmiri patients with venous thromboembolism., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction Venous thromboembolism (VTE) remains a major public health issue around the world. Ethnicity is known to alter the incidence of VTE. To our knowledge, there are no reports in the literature investigating the incidence of VTE in British Indians. The aim of this study was to investigate the rates of symptomatic VTE in British Indian patients in the UK. Methods Patients referred to our institution between January 2011 and August 2013 with clinically suspected VTE were eligible for inclusion in the study. Those not of British Indian or Caucasian ethnicity were excluded. A retrospective review of these two cohorts was conducted. Results Overall, 15,529 cases were referred to our institution for suspected VTE. This included 1,498 individuals of British Indian ethnicity. Of these, 182 (12%) had confirmed VTE episodes. A further 13,159 of the patients with suspected VTE were coded as Caucasian, including 2,412 (16%) who had confirmed VTE events. VTE rates were a third lower in British Indians with clinically suspected VTE than in the equivalent Caucasian group. The British Indian cohort presented with VTE at a much earlier age than Caucasians (mean 57.0 vs 68.0 years). Conclusions This study suggests that British Indian patients have a lower incidence of VTE and are more likely to present at an earlier age than Caucasians. There was no significant difference in VTE type (deep vein thrombosis vs pulmonary embolism) among the ethnic groups. Clinicians should be aware of variations within ethnicities but should continue to adhere to existing VTE prevention guidance.

Essentials Atrial fibrillation (AF) may increase risk of venous thromboembolism (VTE), and vice versa. Bidirectionality was assessed prospectively via data from 15 129 black and white individuals. AF was associated with greater risk of developing VTE, and VTE with greater risk of AF. Associations were strongest among blacks and in the first 6 months after initial diagnosis., Summary: Background Atrial fibrillation (AF) and venous thromboembolism (VTE) frequently co-occur. These conditions have shared risk factors and are accompanied by coagulation abnormalities. Furthermore, mechanistic pathways may directly link the disorders. Objectives To test the hypothesis that individuals with incident AF are at greater risk of developing VTE, and those with VTE are at elevated risk of AF. We also tested whether associations were stronger in the first 6 months after the initial diagnosis, and explored race differences. Patients/Methods A total of 15 129 ARIC study participants (45-64 years, 55% female, 26% Black) were followed from 1987 to 2011 for incident AF and VTE (median follow-up 19.8 years). Multivariable-adjusted Cox regression was used, with AF and VTE modeled as time-dependent exposures. Results Incident AF was associated with greater risk of subsequent incident VTE (hazard ratio [95% CI], 1.71 [1.32-2.22]); the association was stronger in Black people (2.30 [1.48-3.58]) and during the first 6 months after AF diagnosis (5.08 [3.08-8.38]). Similarly, incident VTE was associated with increased risk of incident AF (1.73 [1.34-2.24]), especially in Black people (2.40 [1.55-3.74]) and in the first 6 months after VTE diagnosis (4.50 [2.61-7.77]). Conclusions The occurrence of AF was associated with increased risk of incident VTE, and occurrence of VTE was associated with greater risk of incident AF. Associations were particularly strong among Black people and during the first 6 months after the initial diagnosis, although they remained elevated even after 6 months. These findings highlight patient populations that may be at increased risk of AF and VTE, and perhaps should be targeted with preventive strategies., (© 2018 International Society on Thrombosis and Haemostasis.)

Background/objective: Deep vein thrombosis (DVT) was thought to be uncommon in Asians and routine thromboprophylaxis in the form of anticoagulation for surgical patients was considered to be unnecessary. The current study aims to provide a contemporary epidemiology of venous thromboembolism in a population-based scale., Methods: Information from January 1, 2010 to December 31, 2011 was retrieved from a centralized computer public healthcare database serving mainly an ethnic Han Chinese population of 7.1 million. The incidence, demographics, and hospital mortality rates of DVT and pulmonary embolism (PE) were obtained, and analyzed for different surgical categories., Results: The overall annual incidences of DVT, PE alone, and PE with DVT were 30.0 per 100,000 population, 8.7 per 100,000 population, and 3.0 per 100,000 population, respectively. Overall male to female ratio was 1:1.24. Venous thromboembolic disease was more common with increasing age in both sexes. Thirty days' mortality rates associated with DVT, PE alone, and PE with DVT were 9.0%, 17.4%, and 13.3% respectively. Among the patients who received 103,023 major and intermediate surgical procedures in the study period, the mean incidence of postoperative DVT, PE alone, and PE with DVT were only 0.20% (203.5 patients), 0.08% (85.5 patients), and 0.04% (40.5 patients) respectively., Conclusion: Compared with a similar study 10 years ago, there seemed to be a general increase in incidence of DVT and PE. This study showed that postoperative thromboembolic events were not uncommon, with DVT occurring in up to 0.2% of patients and PE in 0.12% of patients in this longitudinal survey., (Copyright © 2016. Published by Elsevier Taiwan.)

To identify novel single nucleotide polymorphisms (SNPs) associated with venous thromboembolism (VTE) in African-Americans (AAs), we performed a genome-wide association study (GWAS) of VTE in AAs using the Electronic Medical Records and Genomics (eMERGE) Network, comprised of seven sites each with DNA biobanks (total ~39,200 unique DNA samples) with genome-wide SNP data (imputed to 1000 Genomes Project cosmopolitan reference panel) and linked to electronic health records (EHRs). Using a validated EHR-driven phenotype extraction algorithm, we identified VTE cases and controls and tested for an association between each SNP and VTE using unconditional logistic regression, adjusted for age, sex, stroke, site-platform combination and sickle cell risk genotype. Among 393 AA VTE cases and 4,941 AA controls, three intragenic SNPs reached genome-wide significance: LEMD3 rs138916004 (OR=3.2; p=1.3E-08), LY86 rs3804476 (OR=1.8; p=2E-08) and LOC100130298 rs142143628 (OR=4.5; p=4.4E-08); all three SNPs validated using internal cross-validation, parametric bootstrap and meta-analysis methods. LEMD3 rs138916004 and LOC100130298 rs142143628 are only present in Africans (1000G data). LEMD3 showed a significant differential expression in both NCBI Gene Expression Omnibus (GEO) and the Mayo Clinic gene expression data, LOC100130298 showed a significant differential expression only in the GEO expression data, and LY86 showed a significant differential expression only in the Mayo expression data. LEMD3 encodes for an antagonist of TGF-β-induced cell proliferation arrest. LY86 encodes for MD-1 which down-regulates the pro-inflammatory response to lipopolysaccharide; LY86 variation was previously associated with VTE in white women; LOC100130298 is a non-coding RNA gene with unknown regulatory activity in gene expression and epigenetics.

The American College of Chest Physicians (ACCP) has established guidelines for the treatment of VTE, but the generalizability to all populations is unclear. In this review we analyzed the rate of reporting and enrollment of blacks and women in clinical trials cited in the ACCP guidelines for treatment of unprovoked VTE. We extracted data from clinical trials cited by the ACCP that compared durations of anticoagulation therapy for the treatment of unprovoked VTE. We excluded trials that treated surgical or cancer patients. For trials that did not report race/ethnicity we contacted the primary investigators via email for enrollment data. The final analysis included 17 randomized clinical trials with a total patient population of N = 13,693. All trials reported data on sex; conversely, 2 trials (11.8 %) reported race/ethnicity within the primary manuscript. We ultimately acquired data on race/ethnicity from the primary investigator in 5 additional trials for a total race/ethnicity data from 7 trials. There were 7573 males (55.3 %) and 6120 females (44.7 %) enrolled in these studies. Among trials that reported race and ethnicity the total patient population was N = 5368; 5171 (96.3 %) white, 115 (2.1 %) black, 65 (1.4 %) Asian and 7 (0.25 %) Hispanic. Racial/ethnic minorities are underreported and under represented in clinical trials forming the cornerstone of ACCP guidelines for the optimal duration for VTE treatment. Conversely, the reporting and inclusion of women was substantive. The guidelines for unprovoked VTE treatment may not be generalizable to racially and ethnically diverse patient populations.

Background: Asians, Pacific Islanders and Maori have significantly lower rates of venous thromboembolism (VTE) compared to Europeans, but its clinic implication regarding diagnosis and prevention is unclear., Aims: To investigate if ethnicity affects the yield of computed tomography pulmonary angiography (CTPA) and ultrasonography of the lower limbs., Methods: Data previously collected for 523 patients from another study were used to analyse the effect of ethnicity on the results of CTPA; 1587 consecutive ultrasonography of lower limbs was retrospectively analysed according to ethnicity. The Wells score was retrospectively calculated to determine the pretest probability of VTE., Results: The positive rates of CTPA were 23.3% for European patients and 9.3% for non-European patients. The rate ratio was 2.50 (confidence interval [CI] 1.27-4.95). European patients were 2.5 times more likely to have a positive scan result than non-Europeans, given same pretest probability. There was a larger difference among patients with low and moderate pretest probability with a rate ratio of 4.27 (CI 1.62-11.3). The positive rates of ultrasound scans (USS) among European patients were 16.6 and 9.0% for non-European patients. Rate ratio was 1.85 (CI 1.27-4.95). The difference was also more significant amongst patients with low and moderate pretest probability. The rate ratio was 2.31 (CI 1.38-3.86) for European patients compared to non-European patients., Conclusion: Given the same pretest probability according to the Wells score, European patients had significantly higher positive rates of CTPA and ultrasonography of the lower limbs than non-European patients. Further prospective studies are required to confirm our findings and establish an appropriate pretest assessment tool for non-European patients., (© 2016 Royal Australasian College of Physicians.)

Background and Objective: There is little report concerning risk characteristics of Chinese patients with venous thromboembolism (VTE). The present study was designed to investigate the risk characteristics in Chinese patients with VTE through a retrospective study., Methods: A total of 1048 registry patients with VTE in the recent 10 years were analyzed retrospectively with respect to underlying diseases or predisposing factors., Results: The incidence of VTE in both male and female has been increasing in the recent 10 years. A total of 885 patients were aged more than 50 years, and the mean age of the patients at diagnosis was 58.8 ± 15.7 years. Main risk factors were a prolonged immobilization and malignant tumors, which were different from Western patients., Conclusions: This registry demonstrated the different risk characteristics in Chinese patients compared to Western patients. Our results will be available for establishing the prevention of VTE in China., (© The Author(s) 2015.)

Distribution of hereditary thrombophilic gene mutations differs globally. Prothrombin gene mutation G20210A is a common prothrombotic single-nucleotide polymorphism. In this systematic review, we provide a comprehensive report of the prevalence of prothrombin G20210A across the globe. Databases [Pubmed, Web of Science, Embase] were interrogated from their inception through December 2015 for articles reporting prothrombin G20210A prevalence rates and ethnicity. Prevalence rates were organized by continent and ethnoracial ancestry. A total of 113 articles were included with a total 61 876 participants tested for prothrombin G20210A. Reported prevalence rates varied from 0 to 15.9% among ethnic groups, with higher rates seen in the thromboembolism affected cohort compared with the unaffected cohort. Carrier rate distribution is supported by known historical migration patterns of global populations. This review of prothrombin G20210A prevalence may guide resourceful screening for identification of hereditary thrombophilia in female populations of interest with hypercoagulable states.

Venous thromboembolism (VTE) is the third most common life-threatening cardiovascular condition in the United States, with African Americans (AAs) having a 30% to 60% higher incidence compared with other ethnicities. The mechanisms underlying population differences in the risk of VTE are poorly understood. We conducted the first genome-wide association study in AAs, comprising 578 subjects, followed by replication of highly significant findings in an independent cohort of 159 AA subjects. Logistic regression was used to estimate the association between genetic variants and VTE risk. Through bioinformatics analysis of the top signals, we identified expression quantitative trait loci (eQTLs) in whole blood and investigated the messenger RNA expression differences in VTE cases and controls. We identified and replicated single-nucleotide polymorphisms on chromosome 20 (rs2144940, rs2567617, and rs1998081) that increased risk of VTE by 2.3-fold (P< 6 × 10(-7)). These risk variants were found in higher frequency among populations of African descent (>20%) compared with other ethnic groups (<10%). We demonstrate that SNPs on chromosome 20 are cis-eQTLs for thrombomodulin (THBD), and the expression of THBD is lower among VTE cases compared with controls (P= 9.87 × 10(-6)). We have identified novel polymorphisms associated with increased risk of VTE in AAs. These polymorphisms are predominantly found among populations of African descent and are associated with THBD gene expression. Our findings provide new molecular insight into a mechanism regulating VTE susceptibility and identify common genetic variants that increase the risk of VTE in AAs, a population disproportionately affected by this disease.

Pancreatic cancer (PC) is known to be frequently associated with venous thromboembolism (VTE). Although treatment and prophylaxis strategies for VTE in PC patients were updated recently, these were mainly based on data from Western populations and were not verified in East Asian ethnic populations.We investigated the clinical characteristics of VTE in East Asian PC patients. We reviewed electronic medical records (EMR) of 1334 patients diagnosed with pancreatic adenocarcinoma from 2005 to 2010 at single tertiary hospital in Korea. All the patients with newly diagnosed VTE were classified by anatomical site and manifestation of symptoms. The primary outcomes of interest were 2-year cumulative incidence of VTE events. Cox proportional hazards models were used to analyze associations between risk factors and clinical outcomes.A total of 1115 patients were eligible for enrollment. The 2-year cumulative VTE incidence was 9.2%. Major risk factors associated with VTE event were advanced cancer stage, major surgery, and poor performance status. Risk factors associated with mortality after PC diagnosis included advanced cancer stage, poor performance score, leukocytosis, and lower albumin level. The overall VTE did not affected mortality. However in subgroup analysis, symptomatic VTE and deep vein thrombosis/pulmonary thromboembolism (DVT/PTE) showed worse prognosis than incidental or intra-abdominal VTE.The overall incidence of VTE events in Korean PC patients was lower than previous studies. Advanced cancer stage was the most important factor for VTE event and mortality. Unlike Western population group, VTE event did not affect overall prognosis after PC diagnosis. However, symptomatic VTE and DVT/PTE showed higher mortality after VTE event., Competing Interests: The authors have no conflicts of interest to disclose.

Unlabelled: ESSENTIALS: There is little prospective information on genetic risk scores to predict venous thromboembolism (VT). Community based cohort followed a median of 22.6 years for VT occurrence. A 5-SNP risk score identified whites at risk of VT, but not African Americans. The utility of genetic risk scores for VT is yet to be established., Background: Case-control studies have created genetic risk scores of single nucleotide polymorphisms (SNPs) associated with venous thromboembolism (VTE) and documented their ability to predict VTE, but prospective data are lacking., Objective: To test the ability of a genetic risk score to predict VTE incidence in a prospective study, particularly in African Americans., Methods: We computed a previously proposed genetic risk score, based on five established VTE SNPs in the F5, F2, ABO, FGG, and F11 genes, in 9520 whites and 3049 African Americans initially free of VTE. We followed them a median of 22.6 years for VTE occurrence (n = 380 events in whites and n = 187 in African Americans)., Results: In whites, the five-SNP weighted genetic risk score ranged from 0 to 5.8, and VTE risk increased 1.41-fold (95% confidence interval [CI] 1.27-fold to 1.56-fold) per allele increment. In African Americans, the weighted genetic risk score ranged from 0 to 4.6 and the hazard ratio per risk allele was 1.14 (95% CI 0.94-1.38), with adjustment for 10 principal components of ancestry. The area under the receiver operating characteristic curve for 20-year prediction of VTE from the weighted genetic risk score was 0.59 (95% CI 0.56-0.63) in whites and 0.56 (95% CI 0.51-0.61) in African Americans. Adding non-genetic factors increased the area under the curve to 0.67 in whites and to 0.66 in African Americans., Conclusions: Higher values for a five-SNP genetic risk score helped identify white adults at risk of VTE. The genetic risk score did not identify future VTE occurrence in African Americans., (© 2015 International Society on Thrombosis and Haemostasis.)

Elevated plasma concentrations of coagulation factor XI may increase risk of venous thromboembolism (VTE), but prospective data are limited. We studied prospectively the associations of plasma factor XI and a key F11 genetic variant with incident VTE in whites and African-Americans. We measured factor XI in 16,299 participants, initially free of VTE, in two prospective population cohorts. We also measured the F11 single nucleotide polymorphism rs4241824, which a genome-wide association study had linked to factor XI concentration. During follow-up, we identified 606 VTEs. The age, race, sex, and study-adjusted hazard ratio of VTE increased across factor XI quintiles (P < 0.001 for trend), and the hazard ratio was 1.51 (95% CI 1.16, 1.97) for the highest versus lowest quintile overall, and was 1.42 (95% CI 1.03, 1.95) in whites and 1.72 (95% CI 1.08, 2.73) in African-Americans. In whites, the F11 variant was associated with both factor XI concentration and VTE incidence (1.15-fold greater incidence of VTE per risk allele). In African-Americans, these associations were absent. In conclusion, this cohort study documented that an elevated plasma factor XI concentration is a risk factor for VTE over extended follow-up, not only in whites but also in African-Americans. In whites, the association of the F11 genetic variant with VTE suggests a causal relation, but we did not observe this genetic relation in African-Americans., (© 2015 Wiley Periodicals, Inc.)

Genetic susceptibility is considered as a crucial factor for the development of venous thromboembolism (VTE). Epidemiologic and genetic studies have revealed clear disparities in the incidence of VTE and the distribution of genetic factors for VTE in populations stratified by ethnicity worldwide. While gain-of-function polymorphisms in the procoagulant genes are common inherited factors in European-origin populations, the most prevalent molecular basis for venous thrombosis in Asians is confirmed to be dysfunctional variants in the anticoagulant genes. With the breakthrough of genomic technologies, a set of novel common alleles and rare mutations associated with VTE have also been identified, in different ethnic groups. Several putative pathways contributing to the pathogenesis of thrombophilia in populations of African-ancestry are largely unknown, as current knowledge of hereditary and acquired risk factors do not fully explain the highest risk of VTE in Black groups. In-depth studies across diverse ethnic populations are needed to unravel the whole genetics of VTE, which will help developing individual risk prediction models and strategies to minimise VTE in all populations.

Background: Chronic venous disease is common and shares some risk factors with venous thromboembolism (VTE). Several genetic loci have been discovered and well-replicated for VTE in European descent populations. We examined associations of a genetic risk score (GRS), comprising known VTE loci, with chronic venous disease., Methods: The San Diego Population Study (SDPS) is a multi-ethnic cohort that evaluated 2404 men and women aged 29-91 from 1994 to 1998 for chronic venous disease. The current study includes 1447 participants genotyped for 33 variants in 22 established VTE risk loci. Using these variants, unweighted and weighted GRS were constructed. Logistic regression was used to examine associations with venous disease., Results: In non-Hispanic whites, African-Americans, Hispanics, and Asians, each standard deviation increment higher of the unweighted 33-SNP GRS was associated with a 1.45-fold (95% CI (1.26, 1.67)), 1.74-fold (1.18, 2.55), a 1.80-fold (1.30, 2.51), and 1.88-fold (1.30, 2.73) greater odds, respectively, for moderate plus severe disease. The difference in c-statistics was significant between a known venous risk factor model and a model adding the 33-SNP GRS for whites (p=0.008), African-Americans (0.03), and Hispanics (p=0.04), with marginal significance in Asians (p=0.06)., Conclusions: GRS comprising variants primarily from VTE findings in European descent populations were associated with chronic venous disease across all race/ethnic groups, and contributed significantly to prediction, indicating some level of generalizability to other race/ethnic groups. Future work should focus on more in depth examination of racial/ethnic group genetic architecture in relation to chronic venous disease., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The aim of the present study was to reveal the contribution of single nucleotide polymorphisms of the interleukin‑6 (IL‑6) gene and the progression of venous thromboembolism (VTE). A case‑control study composed of 246 VTE patients, including 160 from the Han population (76 males and 84 females, mean age 57.41±13.25 years), 86 from the Uyghur population (41 males and 45 females, mean age 51.61±13.73 years) and 292 gender and ethnicity‑matched control participants, including 170 from the Han population (91 males and 79 females, mean age 55.82±11.83 years) and 122 from the Uyghur population (64 males and 58 females, mean age 53.52±13.64 years) were enrolled in the present study. The results demonstrated that the serum levels of IL‑6, C‑reactive protein (CRP), D‑dimer, fibrinogen, plasminogen activator inhibitor‑1 and leptin were significantly higher in the VTE group compared with the control group (P<0.05). The frequencies of the ‑572C/G promoter polymorphisms of the IL‑6 genotypes CC, CG and GG were identified to be 34, 48 and 18% in the Han population and 33, 47 and 20% in the Uyghur population, respectively. The allele frequency distributions of the C and G alleles were 58 and 42% in the Han population and 56 and 43% in the Uyghur population, respectively. Significant differences were identified in the ‑572C/G promoter polymorphisms between the VTE group and the control group (P<0.05). For the ‑597G/A polymorphism, all individuals carried the GG and GA genotype; AA genotypes were not detected. Logistic regression analysis was used to identify the risk factors for VTE, adjusting by confounding factors, the results of which demonstrated that the CC homozygote of the IL‑6 ‑572G/C, CRP, IL‑6 and high‑density lipoprotein‑cholesterol were independent risk factors of VTE (P<0.05). In conclusion, the ‑572G/C genotype of IL‑6 may be a genetic marker of VTE in the Han and Uyghur populations.

The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and venous thromboembolism (VTE) risk in the Chinese population has been widely reported, but results were inconsistent and underpowered. To elucidate the variable results, a meta-analysis and systematic review were performed from all case-controlled studies relating MTHFR C677T polymorphism by pooling data on them. We estimated the pooled odds ratio with its 95% confidence intervals to assess this possible association. Finally, a total of 24 studies with 2339 cases and 4048 controls were included in the current meta-analysis. Significant association was found with VTE risk for all genetic models. Subgroup analyses by type of VTE further identified the above-mentioned association in deep vein thrombosis/pulmonary embolism and splanchnic vein thrombosis. The findings from our meta-analysis support the associations of MTHFR C677T polymorphism with VTE risk in the Chinese population., (© The Author(s) 2014.)

Background: The American Heart Association's Life's Simple 7 metric is being used to track the population's cardiovascular health (CVH) toward a 2020 goal for improvement. The metric includes body mass index (BMI), blood pressure, cholesterol, glucose, physical activity (PA), cigarette smoking, and diet. We hypothesized a lower risk of venous thromboembolism (VTE) with favorable Life's Simple 7 scores., Methods and Results: REGARDS recruited 30,239 black and white participants ≥45 years of age across the United States in 2003-2007. A 14-point summary score for Life's Simple 7 classified participants into inadequate (0 to 4 points), average (5 to 9 points), and optimal (10 to 14 points) categories. Hazard ratios (HRs) of incident VTE were calculated for these categories, adjusting for age, sex, race, income, education, and region of residence. For comparison, HRs of VTE were calculated using the Framingham 10-year coronary risk score. There were 263 incident VTE cases over 5.0 years of follow-up; incidence rates per 1000 person-years declined from 2.9 (95% confidence interval [CI], 2.3 to 3.7) among those in the inadequate category to 1.8 (95% CI, 1.4 to 2.4) in the optimal category. Compared to the inadequate category, participants in the average category had a 38% lower VTE risk (95% CI, 11 to 57) and participants in the optimal category had a 44% lower risk (95% CI, 18 to 62). The individual score components related to lower VTE risk were ideal PA and BMI. There was no association of Framingham Score with VTE., Conclusions: Life's Simple 7, a CVH metric, was associated with reduced VTE risk. Findings suggest that efforts to improve the population's CVH may reduce VTE incidence., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: The results of various studies attempting to assess the risks of venous thromboembolism in liver cirrhosis have been conflicting. Furthermore, although the incidence of venous thromboembolism is thought to be low in Asians, the relationship between venous thromboembolism and liver cirrhosis has not been investigated in Asian countries., Objective: We investigated the risks of venous thromboembolism in cirrhotic patients in Taiwan to evaluate whether the risk is higher than in the general population., Methods: The data from 1,000,000 National Health Insurance beneficiaries were utilized. All adult beneficiaries were followed from 1 January 2007 to 31 December 2010 to identify those who developed venous thromboembolism. Each identified patient with liver cirrhosis was matched with 10 non-cirrhotic patients on the basis of high-dimensional propensity score. Cox regression models were applied to compare the hazards of venous thromboembolism in the matched cohorts., Results: A total of 757,940 patients were enrolled. After matching, 2223 cirrhotic patients and 22,230 non-cirrhotic patients were selected. The adjusted hazard ratio of venous thromboembolism was significantly increased by having cirrhosis (1.71; 95% confidence interval [CI] 1.05-2.78). A subgroup analysis revealed a much higher hazard ratio of venous thromboembolism in an advanced cirrhosis subgroup (n = 293) than in a matched non-cirrhosis subgroup (n = 2930) (4.36; 95% CI 1.36-14.01)., Conclusion: The risk of venous thromboembolism may be higher in Asian patients with cirrhosis than in the general Asian population, especially in those with advanced cirrhosis., (© 2014 International Society on Thrombosis and Haemostasis.)

Non vitamin K antagonist oral anticoagulants (NOACs) have advantages relative to traditional vitamin K antagonist oral anticoagulants and represents an important advance in the management of patients with atrial fibrillation and venous thromboembolism. Yet it is unclear whether the clinical trials evaluating these agents were inclusive of diverse populations. To assess the inclusion and reporting of race and ethnicity in clinical trials of NOACs across disease states including, atrial fibrillation, venous thromboembolism, and acute coronary syndromes, we queried PubMed and ClinicalTrials.gov for trials of NOACs between 2007 and 2013. We determined the reporting rate and inclusion of the following ethnic groups: whites, blacks, Asians, and Hispanics. We reviewed data from 30 randomized clinical trials of NOACs that enrolled 184,414 patients. Among these trials, 21 (70%) reported race/ethnicity data in the primary manuscript or on ClinicalTrials.gov. Principal investigators provided race/ethnicity data for two additional trials. Enrollment by race included: 109,729 (75.2%) white, 20,901 (14.3%) Asian, 5,718 (3.9%) Hispanic, and 2,941 (2.0%) black. Hispanic ethnicity was only reported in 10 trials. The major clinical trials of NOACs inconsistently reported race/ethnicity and overall black and Hispanic patient enrollment was poor. As such, the relative safety and efficacy of NOACs in minority populations remains uncertain.

The Genetic Markers for Thrombosis (GMT) study compared the relative influence of ethnicity and thrombotic phenotype regarding the distribution of SNPs implicated in haemostasis pathophysiology ("haemostaseome"). We assessed 384 SNPs in three groups, each of 480 subjects: 1) general population of Aquitaine region (Southwestern France) used as control; 2) patients with venous thromboembolism from the same area; and 3) autochthonous Basques, a genetic isolate, who demonstrate unusual characteristics regarding the coagulation system. This study sought to evaluate i) the value of looking for a large number of genes in order to identify new genetic markers of thrombosis, ii) the value of investigating low risk factors and potential preferential associations, iii) the impact of ethnicity on the characterisation of markers for thrombosis. We did not detect any previously unrecognised SNP significantly associated with thrombosis risk or any preferential associations of low-risk factors in patients with thrombosis. The sum of ϰ² values for our 110 significant SNPs demonstrated a smaller genetic distance between patients and controls (321 cumulated ϰ² value) than between Basques and controls (1,570 cumulated ϰ² value). Hence, our study confirms the genetic particularity of Basques especially regarding a significantly lower expression of the non-O blood group (p< 0.0004). This is mitigated by a higher prevalence of factor II Leiden (p< 0.02) while factor V Leiden prevalence does not differ. Numerous other differences covering a wide range of proteins of the haemostaseome may result in an overall different genetic risk for venous thromboembolism.

Background: Sickle cell trait may increase risk of venous thromboembolism, but this is not fully established., Objectives: We sought to determine the association of sickle cell trait with deep vein thrombosis and pulmonary embolism., Methods: Middle-aged African Americans participating in a prospective, population-based cohort investigation, the Atherosclerosis Risk in Communities Study, were followed from 1987 through 2011 for incident hospitalized pulmonary embolism (n = 111) or isolated deep vein thrombosis (n = 138), verified by physician review of medical records. Sickle cell trait (heterozygosity for hemoglobin S, n = 268) was compared with no sickle cell trait (n = 3748)., Results: Over a median of 22 years of follow-up, 249 participants had an incident venous thromboembolism. The hazard ratio of venous thromboembolism was 1.50 (95% confidence interval [CI] 0.96-2.36) for participants with vs. without sickle cell trait, after adjustment for age, sex, ancestry, hormone replacement therapy (women), body mass index, diabetes, and estimated glomerular filtration rate. This hazard ratio was 2.05 (95% CI 1.12-3.76) for pulmonary embolism and 1.15 (95% CI 0.58-2.27) for deep vein thrombosis without pulmonary embolism., Conclusions: Sickle cell trait in African Americans carries a 2-fold increased risk of pulmonary embolism but does not elevate deep vein thrombosis risk. Because neonatal screening for sickle hemoglobin is being conducted in the United States, consideration should be paid to the increased pulmonary embolism risk of individuals with sickle cell trait., (© 2014 International Society on Thrombosis and Haemostasis.)

Background: Venous thromboembolism (VTE) is a major contributor of maternal morbidity and mortality. Whether maternal race/ethnicity is associated with the risk of postpartum VTE remains unclear., Methods and Results: We conducted a population-based, case-control study in Washington State, from 1987 through 2011. Cases comprised all women with selected International Classification of Diseases, Ninth Edition, Clinical Modification codes for hospitalized VTE within 3 months post-delivery. Controls were randomly selected postpartum women who did not experience a VTE. Characteristics of women and their deliveries were abstracted from birth certificates. Using logistic regression models, we compared the risk of postpartum VTE in black, Asian, and Hispanic women with that in non-Hispanic white women, after adjustment for maternal characteristics (age, body mass index, parity, education), pregnancy complications, and delivery methods., Results: Our study comprised 688 cases and 10 246 controls. Among controls, the mean age and body mass index were 27.5 years and 26.3 kg m(-2) , respectively. Compared with white women, black and Asian women had a greater and lower risk of postpartum VTE (adjusted odds ratio [OR] 1.50, 95% confidence interval [CI] 1.10-2.04 and OR 0.67, 95%CI 0.48-0.94, respectively). A lower risk was present in Hispanic women (adjusted OR 0.80, 95% CI 0.61-1.06) but was not statistically significant. In subgroup analyses, we observed an increased risk for black compared with white women among women who delivered via cesarean section (OR 2.03, 95% CI 1.34-3.07) but not among vaginal deliveries (OR 1.03, 95% CI 0.61-1.74)., Conclusions: Maternal race/ethnicity is associated with the risk of postpartum VTE, independently of other risk factors, and should be considered when assessing the use of thromboprophylaxis after delivery., (© 2014 International Society on Thrombosis and Haemostasis.)