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      Sickle Cell Trait: Is There an Increased VTE Risk in Pregnancy and the Postpartum?

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          Abstract

          Blacks are purported to have a higher venous thromboembolism (VTE) risk than whites. We hypothesized that this might be due, in part, to the greater presence of sickle cell trait (SCT) among blacks. We investigated whether the presence of SCT resulted in a higher VTE incidence in a population predisposed to VTE, the pregnant/postpartum women. Methods: Using a mirrored clinical database that prospectively gathered in- and out-patient information for the years 1998–2008, we collected demographic data, including hemoglobin electrophoreses, on all pregnant/postpartum non-Hispanic women who delivered at a large, diverse, urban hospital. We identified those women who developed VTE either while pregnant or postpartum during those 11 years. Charts initially identified as potential VTE cases were subjected to review to ensure accuracy of VTE coding. Results: Of 12,429 women, 679 non-Hispanic SCT black women, 5,465 non-Hispanic Hemoglobin AA (women with HbA as the only hemoglobin present on electrophoresis, with normal amounts of the minor hemoglobins) black women and 1,162 non-Hispanic HbAA white women were included in the analysis. SCT prevalence was high (11.1%) within this black population as compared to 8.3% in the general non-white population. Proportions with VTE were similar for black SCT and black HbAA groups: 0.44% for the SCT group, 0.49% for non-Hispanic black HbAA women. Black HbAA women had a non-significantly higher proportion of VTE than white HbAA women 0.49% vs 0.26% (RR 1.9, 95%CI:0.6,6.3, p = 0.28). Women with VTE were older than those without VTE (32.2 vs. 27.6 years, p = 0.0002) and the majority of VTE occurred postpartum in all groups, and significantly in the HbAA groups. There was no increase in the incidence of pulmonary emboli in the SCT group. Conclusion: In the largest analysis to date, we could not detect a meaningful difference in peripartum VTE incidence between women with and without sickle cell trait.

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          Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study.

          The incidence of venous thromboembolism has not been well described, and there are no studies of long-term trends in the incidence of venous thromboembolism. To estimate the incidence of deep vein thrombosis and pulmonary embolism and to describe trends in incidence. We performed a retrospective review of the complete medical records from a population-based inception cohort of 2218 patients who resided within Olmsted County, Minnesota, and had an incident deep vein thrombosis or pulmonary embolism during the 25-year period from 1966 through 1990. The overall average age- and sex-adjusted annual incidence of venous thromboembolism was 117 per 100000 (deep vein thrombosis, 48 per 100000; pulmonary embolism, 69 per 100000), with higher age-adjusted rates among males than females (130 vs 110 per 100000, respectively). The incidence of venous thromboembolism rose markedly with increasing age for both sexes, with pulmonary embolism accounting for most of the increase. The incidence of pulmonary embolism was approximately 45% lower during the last 15 years of the study for both sexes and all age strata, while the incidence of deep vein thrombosis remained constant for males across all age strata, decreased for females younger than 55 years, and increased for women older than 60 years. Venous thromboembolism is a major national health problem, especially among the elderly. While the incidence of pulmonary embolism has decreased over time, the incidence of deep vein thrombosis remains unchanged for men and is increasing for older women. These findings emphasize the need for more accurate identification of patients at risk for venous thromboembolism, as well as a safe and effective prophylaxis.
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            Pregnancy, the postpartum period and prothrombotic defects: risk of venous thrombosis in the MEGA study.

            Venous thrombosis is one of the leading causes of maternal morbidity and mortality. In the MEGA study, we evaluated pregnancy and the postpartum period as risk factors for venous thrombosis in 285 patients and 857 control subjects. Between March 1999 and September 2004, consecutive patients with a first episode of venous thrombosis were included from six anticoagulation clinics. Partners of patients and a random digit dialing group were included as control subjects. Participants completed a questionnaire and DNA was collected. The risk of venous thrombosis was 5-fold (OR, 4.6; 95% CI, 2.7-7.8) increased during pregnancy and 60-fold (OR, 60.1; 95% CI, 26.5-135.9) increased during the first 3 months after delivery compared with non-pregnant women. A 14-fold increased risk of deep venous thrombosis of the leg was found compared with a 6-fold increased risk of pulmonary embolism. The risk was highest in the third trimester of pregnancy (OR, 8.8; 95% CI, 4.5-17.3) and during the first 6 weeks after delivery (OR, 84.0; 95% CI, 31.7-222.6). The risk of pregnancy-associated venous thrombosis was 52-fold increased in factor V Leiden carriers (OR, 52.2; 95% CI, 12.4-219.5) and 31-fold increased in carriers of the prothrombin 20210A mutation (OR, 30.7; 95% CI, 4.6-203.6) compared with non-pregnant women without the mutation. We found an increased risk of venous thrombosis during pregnancy and the postpartum period, with an especially high risk during the first 6 weeks postpartum. The risk of pregnancy-associated venous thrombosis was highly increased in carriers of factor V Leiden or the prothrombin 20210A mutation.
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              Common susceptibility alleles are unlikely to contribute as strongly as the FV and ABO loci to VTE risk: results from a GWAS approach.

              Venous thromboembolism (VTE) is a complex disease that has a major genetic component of risk. To identify genetic factors that may modify the risk of VTE, we conducted a genome-wide association study by analyzing approximately 317 000 single nucleotide polymorphisms (SNPs) in 453 VTE cases and 1327 controls. Only 3 SNPs located in the FV and ABO blood group genes were found associated with VTE at a genome-wide significant level of 1.7 x 10(-7). Detailed analysis of these SNPs in additional cohorts of more than 1700 cases and 1400 controls revealed that the association observed at the FV locus was the result of the increased risk mediated by the FV Leiden mutation, whereas O and A2 blood groups were found to be at lower risk for VTE. Apart from the FV and ABO loci, no other locus was found strongly associated with VTE. However, using this large cohort of subjects, we were able to replicate the mild effects of 2 nonsynonymous SNPs, rs1613662 in GP6 and rs13146272 in CYP4V2, recently suspected to be associated with VTE.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                22 May 2013
                : 8
                : 5
                : e64141
                Affiliations
                [1 ]Department of Medicine, Mountt Sinai Medical Center, New York, New York, United States of America
                [2 ]Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, United States of America
                [3 ]Department of Medicine, Montefiore Medical Center, Bronx, New York, United States of America
                Wayne State University School of Medicine, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: HHB. Performed the experiments: HHB SP. Analyzed the data: HHB SP HWC. Wrote the paper: SP HHB. Contributed the statistical packages: HWC.

                Article
                PONE-D-13-01295
                10.1371/journal.pone.0064141
                3661437
                23717554
                0617f6ad-7d71-4a42-b207-9165cb7483b1
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 7 January 2013
                : 8 April 2013
                Page count
                Pages: 6
                Funding
                This publication was supported in part by the CTSA Grant UL1 RR025750, KL2 RR025749 and TL1 RR025748 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessary represent the official view of the NCRR or NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine
                Cardiovascular
                Venous Thromboembolism
                Epidemiology
                Cardiovascular Disease Epidemiology
                Genetic Epidemiology
                Hematology
                Hemoglobinopathies
                Sickle Cell Disease
                Obstetrics and Gynecology
                Postpartum Care
                Pregnancy
                Public Health
                Health Screening

                Uncategorized
                Uncategorized

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