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Oral anticoagulants (OACs) are indicated in the first-line treatment of venous thromboembolism (VTE), which comprises of deep vein thrombosis (DVT) and pulmonary embolism (PE). While contemporary guidelines recommend extended-duration anticoagulation after the first diagnosis of unprovoked VTE, the benefits and harms associated with this approach remain unclear across age groups, especially among older adults. Crucially, contemporary estimates of VTE recurrence have not incorporated all-cause mortality as a competing event, the risk of which increases with age. Therefore, we evaluated and synthesized existing literature on of the risk of all-cause mortality by age following completion of limited-duration anticoagulation for a first episode of unprovoked VTE. In addition, we determined the risk of VTE recurrence after completion of limited-duration OAC therapy by age, with death as a competing outcome using data from a prospective cohort study.

Class of 2009 Abstract / OBJECTIVES: To assess whether patients at University Medical Center (UMC) in Arizona who have indications for venous thromboembolism (VTE) prophylaxis receive treatment, determine whether appropriate pharmacologic VTE prophylaxis is implemented, and analyze the incidence of VTE associated with prescribed regimens. METHODS: Data were derived from a retrospective chart review on risk factors for VTE and prescription of pharmacological and non-pharmacological thromboprophylaxis. Two risk assessment models were used to evaluate adherence to treatment standards: the 2008 American College of Chest Physicians (ACCP) evidence-based consensus guidelines and the Caprini score. Clinical outcomes were evaluated with regard to proper thromboprophylaxis including assessment of appropriate time, type, intensity, and duration of treatment. RESULTS: A total of 366 patients met inclusion critera. Based on the Caprini score, 94% of patients were judged to be at risk for VTE. Of those at risk, 90% received thromboprophylaxis; however, only 35% of treated patients received proper thromboprophylaxis. Ten patients (2.7%) experienced a VTE during their hospital stay or within the following 6 months after discharge. There was not a significant difference in incidence of VTE with respect to treatment versus no treatment or proper versus improper prophylaxis (p=0.15 and 0.65, respectively); however, a favorable trend in incidence of VTE was observed for treated patients and patients treated with correct thromboprophylaxis based on risk assessment. CONCLUSIONS: Most patients at UMC who were indicated for VTE prophylaxis received treatment; however, the type, intensity, and duration of thromboprophylaxis were often inappropriate despite the existence of various guidelines.

La maladie thromboembolique veineuse (MTEV) résulte de l’interaction entre des facteurs environnementaux et génétiques. Cinq anomalies constitutionnelles constituent le bilan de thrombophilie (BT) : les déficits en AT, PC et PS, le facteur V Leiden et la mutation de la prothrombine. Seule la moitié des déficits « présumés » en PS trouvent une explication moléculaire. Dans le premier article, seuls les patients présentant une mutation délétère du gène de la PS (PROS1) étaient à risque de MTEV. Seuls des taux <30%, permettaient de dépister les mutations délétères. La mutation Heerlen située sur PROS1 est réputée neutre. Dans le second article, la mutation Heerlen était associée à un risque de MTEV de 6,57. De récentes études ont identifié une trentaine de polymorphismes associés à la MTEV. Cependant, leur impact dans les familles présentant un facteur biologique de risque est méconnu. De même, l’impact de facteurs environnementaux tels que l’obésité et le tabagisme est mal évalué dans ces familles. Dans le troisième article, la prise en compte de 5 facteurs de risque fréquents à effet faible (obésité, tabac, groupe sanguin et deux polymorphismes situés sur F11 et FGG) en complément du dépistage de l’anomalie familiale permettait de mieux caractériser le risque individuel. Nous avons testé la même stratégie dans une population spécifique de femmes sous contraceptifs oraux combinés (4ème article). Trois facteurs de risque fréquents (groupe sanguin, obésité et un polymorphisme de F11) étaient associés à un OR de 13 lorsqu’ils étaient combinés. Au total, la prise en compte de facteurs de risque fréquents à effet faible, permettait une meilleure évaluation du risque individuel. / Venous thromboembolism (VT) results from the interaction between environmental and genetic factors. Five inherited hemostatic defects are part of the thrombophilia screening (TS): AT, PC and PS deficiencies, factor V Leiden and prothrombin mutation. A molecular defect is identified in only half of assumed PS deficiencies. In the first article, only detrimental mutations (DM) located on PROS1 (PS gene) increased VT risk. Only free PS levels below 30% enabled the identification of DM. PS Heerlen mutation located within PROS1 has been considered neutral for a long time. In the second article, the association between PS Heerlen and VT has been tested in a sample of 4173 patients with VT history and 5970 healthy individuals. PS Heerlen was associated with a 6.57 increased risk of VT. Recent genome wide association studies identified nearly 30 polymorphisms associated with VT. However, the impact of such polymorphisms in families with known defects is uncertain. We therefore tested in a third article the association between 11 selected polymorphisms, obesity, smoking and VT in 651 families with known thrombophilia. Considering 5 common risk factors (obesity, smoking, ABO blood group, two polymorphisms located on FGG and F11) together with the TS resulted in a better assessment of VT risk in individuals from families with thrombophilia. We then applied the same strategy in a sample of women using combined oral contraceptives. Three common risk factors (non-O blood groups, obesity and a polymorphism located on F11), when combined, were associated with a 13 OR. In conclusion, considering common risk factors improved the individual assessment of VT risk.

Aims: The Pulmonary Embolism in Syncope Italian Trial reported 17.3% prevalence of pulmonary embolism (PE) in patients admitted with syncope. We investigated the prevalence of venous thromboembolism [VTE, including PE and deep vein thrombosis (DVT)] in syncope vs. non-syncope admissions and readmissions, and if syncope is an independent predictor of VTE. Methods and results: We conducted an observational study of index admissions of the 2013-14 Nationwide Readmission Database. / National Institutes of Health / Revisión por pares

Background: A D-dimer threshold <500ug/L has high negative predictive value (NPV) for venous thromboembolism (VTE), but is non-specific. Two strategies increase the specificity and utility (defined as the proportion of patients with a negative test) of D-dimer testing: 1) using a higher D-dimer threshold with increasing age (IAIT Strategy); and 2) using a high threshold in low clinical pretest probability (CPTP) patients and the standard threshold in moderate CPTP patients (CPTP Strategy). It is unknown whether the gain in specificity of the IAIT Strategy is simply due to using a higher threshold in some patients and whether the CPTP Strategy has better diagnostic accuracy than the IAIT Strategy. Methods: In a retrospective analysis of 1649 outpatients with suspected VTE, I compared the diagnostic accuracy of the IAIT Strategy to 1) its opposite: using a higher D-dimer threshold with decreasing age (DAIT strategy); 2) using a higher D-dimer threshold in all patients (Median Age Strategy); and 3) the CPTP Strategy. Results: The NPV of both the IAIT and DAIT Strategies was 99.6% and the NPV of the Median Age Strategy was 99.7%. The utility was almost identical in the IAIT and DAIT Strategies (50.9% vs. 50.6%) and greater in the Median Age Strategy (53.9%, p<0.001). The NPV of the CPTP and IAIT Strategies were 99.6% and 99.7%, respectively. The utility was higher in the CPTP Strategy than the IAIT Strategy (56.1% vs. 50.9%, p<0.001). Conclusions: The NPV and utility of using a higher D-dimer threshold in older patients (IAIT Strategy) is the same as using a higher D-dimer threshold in younger patients. The CPTP Strategy had the greatest utility while maintaining a high NPV and therefore appeared to be the optimal strategy of D-dimer interpretation. / Thesis / Master of Health Sciences (MSc)

Class of 2012 Abstract / Specific Aims: The purpose of this study was to evaluate the effectiveness of various post-operative prophylaxis methods in lung transplant patients by comparing the incidence of venous thromboembolism (VTE) before and after the implementation of a standardized hospital order set at the University of Arizona Medical Center (UAMC) in April 2007. Methods: Paper and electronic medical charts were retrospectively reviewed if patients had a lung transplant date between October 31, 2003 – October 31, 2010. A computerized database was used to collect demographic data, length of stay (LOS), comorbid conditions, prophylaxis type (including dose/frequency), and date/type of thromboembolic events in the post-operative period prior to discharge and up to 1-year post- discharge. Main Results: Ninety-two patient charts were included in the study with 35 charts in the pre-order set (“Before”) group and 57 charts in the post- order set (“After”) group. All baseline characteristics were similar between groups except age (mean age difference 8.1 yrs, p=0.003), use of mycophenolate (Before n=24, After n=54; p=0.002), and use of medications that increase risk of VTE (Before n=6, After n=2; p=0.05). The April 2007 protocol significantly increased the number of patients receiving any method of prophylaxis (p<0.0001). However, receiving prophlyaxis did not significantly reduce event rates or readmissions due to VTE. Conclusions: Although implementation of the April 2007 protocol did not significantly reduce VTE event rates and readmissions, VTE prophylaxis should continue to remain a priority. Adherence to the implemented protocol may reduce the number of patients left without effective methods of prophylaxis.

No description available.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21621号 / 医博第4427号 / 新制||医||1033(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 湊谷 謙司, 教授 佐藤 俊哉, 教授 横出 正之 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Thesis (Ph. D.)--University of Washington, 2008. / Vita. Includes bibliographical references (leaves 64-74).