A large-scale exome array analysis of venous thromboembolism.

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.

Comparison of 2013 and 2009 versions of Caprini risk assessment models for predicting VTE in Chinese cancer patients: a retrospective study.

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.

Nationwide Trends in Prevalent Cardiovascular Risk Factors and Diseases in Young Adults: Differences by Sex and Race and In-Hospital Outcomes.

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.

Identifying mutation-driven changes in gene functionality that lead to venous thromboembolism.

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.

Association study of miR-146a, miR-149, miR-196a2, and miR-499 polymorphisms with venous thromboembolism in a Korean population.

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.

Novel genetic predictors of venous thromboembolism risk in African Americans.

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.

Venous Thromboembolism Following Total Knee Arthroplasty: Does Race Matter?

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.

Review of venous thromboembolism and race: the generalizability of treatment guidelines for high-risk populations.

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.

Ethnicity as an independent predictive factor for the results of computed tomography pulmonary angiography and ultrasonography of the lower limbs.

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.

Racial and regional differences in venous thromboembolism in the United States in 3 cohorts.

BACKGROUND: Blacks are thought to have a higher risk of venous thromboembolism (VTE) than whites. However, prior studies are limited to administrative databases that lack specific information on VTE risk factors or have limited geographic scope. METHODS AND RESULTS: We ascertained VTE from 3 prospective studies: the Atherosclerosis Risk in Communities Study (ARIC), the Cardiovascular Health Study (CHS), and the Reasons for Geographic and Racial Differences in Stroke study (REGARDS). We tested the association of race with VTE using Cox proportional hazard models adjusted for VTE risk factors. Over 438 090 person-years, 916 incident VTE events (302 in blacks) occurred in 51 149 individuals (17 318 blacks) who were followed up. In risk factor-adjusted models, blacks had a higher rate of VTE than whites in the CHS (hazard ratio, 1.81; 95% confidence interval, 1.20-2.73) but not ARIC (hazard ratio, 1.21; 95% confidence interval, 0.96-1.54). In REGARDS, there was a significant region-by-race interaction (P=0.01): Blacks in the Southeast had a significantly higher rate of VTE than blacks in the rest of the United States (hazard ratio, 1.63; 95% confidence interval, 1.08-2.48) that was not seen in whites (hazard ratio, 0.83; 95% confidence interval, 0.61-1.14). CONCLUSIONS: The association of race with VTE differed in each cohort, which may reflect the different time periods of the studies or different regional rates of VTE. Further studies of environmental and genetic risk factors for VTE are needed to determine which underlie racial and perhaps regional differences in VTE.

Prospective study of circulating factor XI and incident venous thromboembolism: The Longitudinal Investigation of Thromboembolism Etiology (LITE).

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.

Review of race/ethnicity in non vitamin K antagonist oral anticoagulants clinical trials.

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.

Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease.

BACKGROUND: Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease, range from 34% to 50%. Genetic variants so far identified by genome-wide association studies explain only a small proportion (<2%) of its variation. METHODS AND RESULTS: We conducted a meta-analysis of 28 genome-wide association studies including >90 000 subjects of European ancestry, the first genome-wide association meta-analysis of fibrinogen levels in 7 studies in blacks totaling 8289 samples, and a genome-wide association study in Hispanics totaling 1366 samples. Evaluation for association of single-nucleotide polymorphisms with clinical outcomes included a total of 40 695 cases and 85 582 controls for coronary artery disease, 4752 cases and 24 030 controls for stroke, and 3208 cases and 46 167 controls for venous thromboembolism. Overall, we identified 24 genome-wide significant (P<5×10(-8)) independent signals in 23 loci, including 15 novel associations, together accounting for 3.7% of plasma fibrinogen variation. Gene-set enrichment analysis highlighted key roles in fibrinogen regulation for the 3 structural fibrinogen genes and pathways related to inflammation, adipocytokines, and thyrotrophin-releasing hormone signaling. Whereas lead single-nucleotide polymorphisms in a few loci were significantly associated with coronary artery disease, the combined effect of all 24 fibrinogen-associated lead single-nucleotide polymorphisms was not significant for coronary artery disease, stroke, or venous thromboembolism. CONCLUSIONS: We identify 23 robustly associated fibrinogen loci, 15 of which are new. Clinical outcome analysis of these loci does not support a causal relationship between circulating levels of fibrinogen and coronary artery disease, stroke, or venous thromboembolism.

Dysfunction of protein C anticoagulant system, main genetic risk factor for venous thromboembolism in northeast Asians.

Venous thromboembolism (VTE) is a life threatening medical disorder worldwide. A great deal of evidence suggests that prevalence of VTE varies significantly among ethnic populations, with consistently lower incidence found in Asians. While the distribution of genetic risk factors may vary among races, genetic risk factors can play a major role among individuals with different genetic backgrounds. Two clinically evaluated low-frequency genetic mutations that predispose to VTE--the factor V Leiden mutation and prothrombin G20210A mutation--are found predominantly in Caucasians, and virtually never in Asians. The findings of a recent genetic study of VTE in northeast Asians, which greatly advanced our knowledge in this area, indicate that the most frequent genetic risk factors for VTE in northeast Asians can be attributed to a dysfunction of the protein C anticoagulant system. Several low-frequency genetic mutations, PROS1 p.Lys196Glu in Japanese and PROC p.Arg189Trp and p.Lys193del in Chinese, are significantly associated with increased risk for VTE, with odds ratio more than 2 through the reduced protein C anticoagulant activity. Construction of a multifactorial model based on the genetic risk factors in the protein C anticoagulant system could facilitate genetic counseling for VTE risk in these populations. The influence of prevalent genetic mutations on the risk of VTE should be further investigated in Asian countries.

High factor VIII, von Willebrand factor, and fibrinogen levels and risk of venous thromboembolism in blacks and whites.

Venous thromboembolism (VTE) affects more than 300,000 people in the United States each year. However, it has been estimated that current diagnostic testing fails to identify prothrombotic risk in 50% of VTE patients. This article examines the relationship between levels of the pro-coagulant proteins factor VIII (FVIII), von Willebrand factor (VWF), and fibrinogen and risk of VTE in order to assess the impact of these novel risk factors. Data were collected from patients enrolled in the matched case-control Genetic Attributes and Thrombosis Epidemiology study. Crude and adjusted conditional logistic regression models were used to assess the impact of FVIII, VWF, and fibrinogen on risk of VTE. Before adjustment for independent predictors of VTE risk, high levels of FVIII, VWF, and fibrinogen were significantly associated with increased risk of VTE in both Blacks and Whites. After adjustment for ABO type, factor VII levels, hypertension, renal disease, recent surgery, diabetes, annual household income, alcohol use, and the other proteins of interest (FVIII, VWF, and/or fibrinogen), high FVIII and VWF levels were associated with increased risk of VTE in Blacks (OR: 1.97 [1.01-3.84] and 3.39 [1.58-7.27], respectively). High FVIII only was significantly associated with risk of VTE in Whites (OR: 2.35 [1.16-4.75]). Future research into the inclusion of these protein levels in risk models for VTE could help identify persons at highest risk.

Racial, biological sex, and geographic disparities of venous thromboembolism in the United States, 2016 to 2019.

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.

Venous thromboembolism in Black COVID-19 patients in a minority context compared to White, Asian and other racialized patients: A systematic review and meta-analysis.

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.

Association between antidepressants and venous thromboembolism in Taiwan.

OBJECTIVE: To investigate the association between venous thromboembolism (VTE) and antidepressant use in an Asian population. METHODS: The authors conducted a nested case-control study of 1888 patients with VTE and 11,222 matched controls enrolled in the National Health Insurance Research Database in Taiwan from 2001 to 2009. The antidepressant exposure status and potential confounding factors were measured and included in the analyses. Conditional logistic regressions were applied to determine the effect of antidepressant use on VTE. RESULTS: We found a significant association of current antidepressant use with VTE in the total study sample (adjusted odds ratio [aOR], 1.59; 95% confidence interval (CI), 1.27-2.00). With regard to antidepressant classes and potency, we found that tricyclic antidepressants (aOR, 1.56; 95% CI, 1.11-2.18), serotonin 5-HT2A receptor blockers (aOR, 2.03; 95% CI, 1.27-3.24), and antidepressants with a low potency of serotonin reuptake inhibition (aOR, 1.57; 95% CI, 1.18-2.08) were associated with a significantly increased risk of VTE. When further stratifying by age, sex, and comorbid conditions, the VTE risk with antidepressant use was elevated among young and middle-aged adults, but not among the elderly. In addition, an elevated risk of VTE was observed in women and subjects without severe comorbid conditions, but not in men and subjects with severe comorbid conditions. CONCLUSIONS: There was a small increase in VTE risk with antidepressant use. The prescription of antidepressant drugs should be cautious, and especially, should be based on clinical evaluations of benefits and risks. The underlying mechanisms of the interaction between antidepressants and VTE warrant further investigation.