Background: The Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism (RECORD) 1 to 4 trials compared rivaroxaban 10 mg daily with commonly used doses of enoxaparin and demonstrated similar rates of VTE and bleeding. Objective: To evaluate bleeding events between patients who received enoxaparin or rivaroxaban for prevention of venous thromboembolism (VTE) following total hip arthroplasty (THA) or total knee arthroplasty (TKA). Methods: Retrospective cohort that compared patients undergoing THA and TKA who received enoxaparin (enoxaparin) with those who received rivaroxaban (rivaroxaban) and also with those who received enoxaparin in the RECORD 1 to 4 trials (enoxaparin RECORD). The primary outcome was any postoperative bleeding, defined as a composite of major and clinically relevant nonmajor bleeding based on the definitions in the RECORD 1 to 4 trials. Results: There was a lower rate of any postoperative bleeding (2.2% vs 6.8%, P = 0.004) in patients who received enoxaparin compared with rivaroxaban, and bleeding rates between the enoxaparin group and the enoxaparin RECORD groups were similar (2.2% vs 2.5%, P = 0.085). Major bleeding in the enoxaparin group (0.2%) was not significantly different from that in the rivaroxaban group (1.4%, P = 0.12) or the RECORD group (0.2%, P = 0.93). Clinically relevant nonmajor bleeding was also lower in the enoxaparin group compared with the rivaroxaban group (2.0% vs 5.5%, P = 0.012). Conclusions: The use of enoxaparin for VTE prophylaxis following THA and TKA was associated with a lower rate of the primary outcome (any postoperative bleeding) compared with the use of rivaroxaban in a similar cohort of patients.

<p>Venous thromboembolism (VTE), which encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE), is the most preventable cause of death in hospitalized patients. Due to its high mortality, morbidity, and cost, health care providers are obligated to not only effectively diagnose and treat VTE, but also to prevent it if possible. This has been reinforced by a number of national and international quality initiatives to prevent hospital-acquired VTE. Despite the existence of well-accepted clinical practice guidelines on VTE prophylaxis, 1 in 3 hospitalized medical patients receives an inappropriate VTE prophylaxis strategy. Both underuse of prophylaxis in patients with VTE risk, and overuse of prophylaxis in patients without VTE risk are problems. The use of inappropriate VTE prophylaxis strategies is likely due to the complexity and heterogeneity of hospitalized medical patients, and the difficulty of applying “one size fits all” practice guidelines to this group. Institution-wide knowledge translation strategies are required to close the gap between evidence and practice, and promote evidence-based VTE prophylaxis strategies in hospitalized medical patients. The objective of this thesis is to design a cluster randomized controlled trial to determine if a standardized electronic order set, with an embedded computerized decision support system and audit and feedback component, affects the use of appropriate VTE prophylaxis in hospitalized medical patients. The unit of randomization in this study is the hospital, which serves as the cluster. The unit of observation in this study is the individual patient. The primary outcome of this study is the proportion of in-hospital days during which appropriate VTE prophylaxis is administered, in intervention versus control hospitals. Secondary outcomes are the rates of hospital-acquired VTE, major bleeding and mortality, in intervention versus control hospitals. Design, analytic and ethical challenges unique to cluster randomized trials will also be discussed. Strategies to overcome them in this trial will be presented.</p> / Master of Science (MSc)

BACKGROUND:Anticoagulation with vitamin K antagonists such as warfarin has historically been used for the long term management of patients with thromboembolic disease. However, these agents have a slow onset of action which requires bridging therapy with heparin and its analogues, which are available only in parenteral route. To overcome these limitations, new oral anticoagulants such as factor Xa inhibitors and direct thrombin inhibitors have been developed. The aim of this article is to systematically review the phase 3 clinical trials of new oral anticoagulants in common medical conditions.METHODS:We searched PubMed (Medline) from January 2007 to February 2013 using "Oral anticoagulants", "New oral anticoagulants", "Randomized controlled trial", "Novel anticoagulants", "Apixaban", "Rivaroxaban", "Edoxaban", "Dabigatran etexilate", "Dabigatran" and a combination of the above terms. The available evidence from the phase 3 RCTs was summarized on the basis of individual drug and the medical conditions categorized into "atrial fibrillation", "acute coronary syndrome", "orthopedic surgery", "venous thromboembolism" and "medically ill patients".RESULTS:Apixaban, rivaroxaban and dabigatran have been found to be either non-inferior or superior to enoxaparin in prophylaxis of venous thromboembolism in knee and hip replacement with similar bleeding risk, superior to warfarin for stroke prevention in atrial fibrillation with significant reduction in the risk of major bleeding, non-inferior to aspirin for reducing cardiovascular death and stroke in acute coronary syndrome with significant increase in the risk of major bleed. Rivaroxaban and dabigatran are also superior to the conventional agents in the management of symptomatic venous thromboembolism. However, compared to enoxaparin, apixaban and rivaroxaban use lead to significantly increased bleeding risk in medically ill patients. Additional studies evaluating the specific reversal agents of these new drugs for the management of life-threatening bleeding or other adverse effects are necessary.CONCLUSION:Considering their pharmacological properties, their efficacy and bleeding complications, the new oral agents offer a net favourable clinical profile in orthopedic surgery, atrial fibrillation, acute coronary syndrome and increase the risk of bleeding in critically ill patients. Further studies are necessary to determine the long term safety and to identify the specific reversal agents of these new drugs.

Submitted by Silvana Teresinha Dornelles Studzinski (sstudzinski) on 2015-10-26T14:23:08Z No. of bitstreams: 1 Daniela Lopes Jardim.pdf: 816363 bytes, checksum: b7a8c78372004043d222796dbc02face (MD5) / Made available in DSpace on 2015-10-26T14:23:08Z (GMT). No. of bitstreams: 1 Daniela Lopes Jardim.pdf: 816363 bytes, checksum: b7a8c78372004043d222796dbc02face (MD5) Previous issue date: 2015-07-10 / UNISINOS - Universidade do Vale do Rio dos Sinos / O tromboembolismo venoso é responsável por um grande número de complicações hospitalares, ocasionando aumento na média de permanência hospitalar dos pacientes. São duas as condições mais frequentes de tromboembolia venosa, a trombose venosa profunda e o tromboembolismo pulmonar, sendo esta a causa de morte evitável mais comum no paciente hospitalizado. OBJETIVO: Elaborar um protocolo assistencial de enfermagem para a prevenção de tromboembolismo venoso profundo em pacientes cirúrgicos. MATERIAL E MÉTODO: Estudo exploratório de revisão sistemática, com busca em banco de dados da Cochrane, Medical Literature Analysis and Retrieval Sistem Online, Literatura Latino-Americana e do Caribe em Ciências da Saúde e da Scientific Electronic Library Online. Foram utilizados para a busca os descritores e MESH: Venous Thromboembolism, Risk Factores, Guideline, cirurgic patient, surgery, cardiologic surgery e vascular surgery. Para a sistematização das informações foi utilizado o método PICO (Paciente, Intervenção, Comparação e desfechos) e para a análise dos dados o sistema de classificação de Nível de Evidência do Oxford Center for Evidence Based Medicine e a Classificação do Grading of Recommendations Assessment, Development and Evaluation. RESULTADOS: Dos 9.727 artigos, foram selecionados 6.111 da Cochrane, 3.535 do MEDLINE, 55 LILACS e um artigo do Scielo. Após a leitura dos títulos e resumos, 123 artigos encontrados, sendo selecionados 27 artigos da Cochrane, 73 artigos do MEDLINE, um artigo do Scielo e 22 artigos do LILACS. Após aplicar os critérios de inclusão e exclusão, foram selecionados para o estudo 25 artigos. CONCLUSÃO: a construção deste protocolo assegurará qualidade e padronização da avaliação e procedimentos de enfermagem na sistematização do tromboembolismo venoso. Sua efetivação se dará após sua validação e implantação. / Venous thromboembolism is accountable for a large number of hospital complications, while implicating an increased average hospital stay of patients. There are two most common conditions of venous thromboembolism: deep vein thrombosis, and pulmonary embolism, being such thromboembolisms the most common cause of preventable death in hospital patients. PURPOSE: Prepare a clinical protocol of nursing for the prevention of deep venous thromboembolism in surgical patients. MATERIALS AND METHODS: Exploratory study of systematic review, with search in databases as Cochrane, Medical Literature Analysis and Retrieval Sistem Online, Literatura Latino-Americana e do Caribe em Ciências da Saúde e da Scientific Electronic Library Online. For the searching were used the MeSH descriptors Venous Thromboembolism, Risk Factors, Guideline, Surgical Patient, Surgery, Cardiac Surgery, and Vascular Surgery. For the systematization of the data was used the PICO-method (P-patient, I-intervention, C-comparation, O-outcomes), and, for the data analysis, the classification system of the Oxford Centre for Evidence-based Medicine/Levels of Evidence, and the Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Among 9,727 articles, 6,111 were selected from Cochrane, 3,535 from MEDLINE, 55 from LILACS, and 1 from SciELO. After the reading of titles and summaries, 123 articles were taken into account, 27 being selected from Cochrane, 73 from MEDLINE, 1 from SciELO, and 22 from LILACS. Having applied the inclusion and exclusion criteria, 25 articles were selected for the study. CONCLUSION: The construction of this protocol will ensure quality and standardization of the assessment and nursing procedures in the systematization of venous thromboembolism. Its effectiveness will take place after its validation and implementation.

L’identification des facteurs de risque de la maladie thromboembolique veineuse (MVTE) est un enjeu pour la prévention de la maladie et de sa récidive. Nous avons montré chez l’homme que le cumul des facteurs de risque cardiovasculaires d’athérosclérose (FRCV) est associé à la MVTE non provoquée, à sa gravité et au risque de récidive. Le vieillissement, FRCV et facteur de risque de MVTE, induit chez le rat une dysfonction endothéliale de la veine fémorale liée aux cyclooxygénases (COX), associée à la génération de prostanoïdes au profil pro-thrombogène. Chez le rat obèse ZSF1 jeune, le cumul des FRCV induit une dysfonction endothéliale veineuse précoce liée aux COX-1 et 2. Un traitement par Ω-3 chez le rat vieillissant permet de moduler le métabolisme de l’acide arachidonique pour générer des prostanoïdes moins délétères COX-2-dépendants pouvant réduire le risque thrombogène, faisant des Ω-3 un traitement adjuvant potentiel de la MVTE. / Identification of risk factors for venous thromboembolism (VTE) is a major concern for the prevention of the disease and its recurrence. We have shown in humans that the cumulative cardiovascular risk factors (CVFR) for atherosclerosis were associated with unprovoked VTE, its severity and the risk of recurrence. Aging, CVRF and VTE risk factor, induced an endothelial dysfunction in the rat femoral vein involving cyclooxygenases (COX) associated with potential pro-thrombogenic prostanoids generation. In the young obese ZSF1 rat, cumulative CVRF induced early venous endothelial dysfunction related to COX-1 and 2. Omega-3 treatment in aging rats modulates arachidonic acid pathway leading to COX-2-mediated formation of less deleterious prostanoids, associated with a decreased thrombogenic risk, making omega-3 a potential adjuvant treatment for VTE.

Venous thromboembolism (VTE) is a common cardiovascular disease that frequently recurs and is associated with significant numbers of death annually. The influence of the hereditary risk factors is not yet firmly established but twin and family studies suggest that heritability is about 50%. Several genetic risk factors have been identified by genomeHwide association studies (GWAS) but they do not explain all of the missing heritability of VTE. NextHgeneration sequencing (NGS) has revolutionized the genetic analysis of disease and has been used to discover the genes underlying unsolved Mendelian disorders. It has also been used to identify rare alleles which may help explain the missing heritability for complex diseases. The study population of this study consisted of 32 randomly chosen VTE patients from the MATSHstudy (Malmö Thrombophilia Study). The seventeen genes that in earlier studies have been shown to be associated with VTE were examined and the identified VTEHrelated mutations were compared to the general population. The results showed that Ion TorrentHsequencing effectively provided good coverage and read depth in all of the sequenced genes. Optimization of the primer panels resulted in higher and more balanced coverage and the quality of the results in this study was on an overall high level. A total of 215 variants were detected – 62 in exons, 8 in splice and 145 in introns. One Mendelian mutation was detected in PROC and rare variants were found in F2 and FGG. The most common risk factor (F5 Leiden) was highly enriched with 25% in this study compared to 3% in a background population. / Venös tromboembolism (VTE) är en vanlig, ofta återkommande, kardiovaskulär sjukdom som associeras med åtskilliga dödsfall årligen. De ärftliga riskfaktorernas påverkan är inte fullständigt kartlagda ännu men tvillingH och familjestudier antyder att ärftligheten kan vara runt 50%. Ett flertal genetiska riskfaktorer har identifierats genom genome$wide association studies (GWAS) men de förklarar inte hela den saknade ärftlighetskomponenten för VTE. NästaHgenerationsHsekvensering (NGS) har revolutionerat den genetiska sjukdomsanalysen och har använts för att upptäcka de gener som ligger bakom tidigare olösta Mendelska sjukdomstillstånd. Man har även använt NGS för att identifiera rara alleler som kan hjälpa till att förklara de saknade ärftlighetskomponenterna för nedärvning av komplexa sjukdomar. Studiepopulationen I den här undersökningen utgjordes av 32 slumpmässigt utvalda VTEHpatienter från Malmö Thrombophilia Study (MATS). De sjutton gener som I tidigare studier har visat sig vara associerade med VTE undersöktes och de identifierade VTEHrelaterade mutationerna jämfördes med en normalpopulation. Resultaten visade att Ion TorrentHsekvensering ger bra täckningsgrad och läsdjup i alla de sekvenserade generna. Optimering av primerHpanelerna resulterade i en mer balanserad täckningsgrad och resultatkvaliteten i den här studien var på en generellt hög nivå. Totalt 215 varianter detekterades – 62 i exon, 8 i splice och 145 i introner. En Mendelsk mutation detekterades I PROC och rara varianter hittades i F2 och FGG. Den starkaste och vanligaste riskfaktorn (F5 Leiden) var högt anrikad i den här studien med 25% jämfört med 3% i en bakgrundspopulation.

Orientador: Joyce Maria Annichinno-Bizzacchi / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-08T02:29:39Z (GMT). No. of bitstreams: 1 Mello_TayanaBezerraTeixeira_D.pdf: 2343820 bytes, checksum: be3d8e4b057cd84ec6771c67b8b1407d (MD5) Previous issue date: 2006 / Resumo: Nos últimos anos tem sido demonstrada uma associação entre níveis elevados de certos fatores da coagulação e risco de tromboembolismo venoso (TEV). Entretanto, o número de estudos é pequeno e a maioria estão restritos a populações caucasóides. Neste estudo caso-controle emparelhado por idade, sexo e etnia investigamos os níveis plasmáticos do fibrinogênio, FVII, FVIII, FIX, FX, FXI, FvW e grupo sanguíneo (GS) ABO no risco trombótico. Foram analisados 175 pacientes com TEV (122 mulheres e 53 homens), com idade mediana de 36 anos (13-63), acompanhados no Ambulatório de Hemostasia da Unicamp no período de julho de 2002 a julho de 2005. Na análise univariada, níveis elevados de FVIII (OR: 5,3 IC95% 2,9-9,6), FvW (OR: 4,9 IC95% 2,7-8,9), FIX (OR: 2,4 IC95% 1,3-4,4), FXI (OR: 2,1 IC95% 1,1-4,0) e GS não O (OR: 3,0 IC95% 1,9-4,6) foram fatores de risco para TEV. O FVIII, FvW e GS não O foram associados ao risco tanto em membro inferior como em sítio incomum da doença. A análise de todas estas variáveis, segundo critério de seleção ¿stepwise¿, mostrou o FVIII (OR: 3,1 IC95% 1,6-6,0), FvW (OR:2,8 IC95% 1,4-5,4) e o GS não-O (OR:2,2 IC95% 1,3-3,5) como fatores de risco independentes para TEV e que o FIX e FXI agiram sinergicamente a estas variáveis no acréscimo do risco trombótico. Risco de recorrência foi conferido por elevações do FIX (OR: 4,7 IC95% 1,8-11,9) e FXI (OR: 3,4 IC95% 1,8-8,7). Os determinantes dos níveis plasmáticos do FVIII não estão totalmente esclarecidos. Como a LRP (Low density lipoprotein receptor related protein) tem um papel no catabolismo do FVIII, foram pesquisados os polimorfimos C200T, o A775P e o D2080N no gene codificador dessa proteína, como fator de risco para TEV e a influência dos mesmos sobre os níveis do FVIII e FvW. Não houve diferença nas prevalências destes polimorfismos entre pacientes e controles. No entanto, no grupo-controle, o genótipo DN, do polimorfismo D2080N, foi associado a menores concentrações do FVIII (77,4 UI/dl) e FvW (70,2 UI/dl), quando comparado ao genótipo DD (127 UI/dl e 108,4 UI/dl, respectivamente p<0,05). Em conclusão, nesta população brasileira miscigenada, o FVIII, FvW , FIX, FXI e GS não O foram associados ao risco de TEV e o polimorfismo D2080N, no gene da LRP, interferiu com os níveis plasmáticos de FVIII e FvW / Abstract: During the last years an association between high levels of certain coagulation factors and the risk for venous thromboembolism (VTE) has been demonstrated. The number of studies, however, is small, and most of them are restricted to Caucasian populations. In this case control study, matched for age, sex and ethnicity, we investigated the plasma levels of fibrinogen, FVII, FVIII, FIX, FX, FXI, vWF and the ABO blood group (BG) in the thrombotic risk. It was analyzed 175 patients with VTE (122 women and 53 men), median age 36 years (13-63), followed at the hemostasis outpatient clinic at the State University of Campinas ¿ UNICAMP, between July 2002 and July 2005. In univariate analysis, elevated levels of FVIII (OR: 5.3 95%CI 2.9-9.6), FvW (OR: 4.9 95%CI 2.7-8.9), FIX (OR: 2.4 95%CI 1.3-4.4), FXI (OR: 2.1 95%CI 1.1-4.0) and non O BG (OR: 3.0 95%CI 1.9-4.6) were risk factors for VTE. FVIII, FvW and non O BG were associated with the risk both in lower limbs and unusual sites of disease. Analysis of all these variables by stepwise selection criteria showed FVIII (OR:3.1 95%CI 1.6-6.0), FvW (OR:2.8 95%CI 1.4-5.4) and non O BG (OR:2.2 95%CI 1.3-3.5) as independent risk factors for VTE, and FIX and FXI increased synergistically the risk of thrombosis of these variables. Risk of recurrence was conferred by FIX (OR:4.7 IC95% 1.8-11.9) and FXI (OR:3.4 IC95% 1.8-8.7). The FVIII plasma levels determinants are not well established. Since LRP (Low density lipoprotein receptor related protein) has a role in the catabolism of FVIII, we evaluated the C200T, A775P and, D2080N polymorphisms in the gene coding of this protein, as risk factor for VTE and their influence upon the levels of FVIII and vWF. There was no difference regarding the prevalence of these polymorphisms between patients and controls. However, in the control group, the DN genotype, of the D2080N polymorphism, was associated with lower concentrations of FVIII (77.4 UI/dl) and vWF (70.2 UI/dl), when compared to DD genotype (127 UI/dl e 108.4 UI/dl, respectively p<0.05). In conclusion, in these Brazilian miscigenous population, increased levels of FVIII, FvW, FIX, FXI and non O BG were associated with VTE risk and the D2080N polymorphism, in the LRP gene, influenced plasma levels of FVIII and vWF / Doutorado / Biologia Estrutural, Celular, Molecular e do Desenvolvimento / Doutor em Fisiopatologia Medica

Orientador: Carmen Maria Casquel Monti Juliani / Resumo: Objetivos: caracterizar o risco de tromboembolismo venoso e o uso de profilaxia em pacientes clínicos e cirúrgicos, avaliando a conformidade ou não-conformidade da prescrição de profilaxia medicamentosa e desvelar a percepção dos enfermeiros frente ao uso do protocolo de profilaxia de tromboembolismo venoso. Métodos: Estudo descritivo, com abordagem multimétodos ou método misto, utilizando técnicas quantitativas (estudo transversal) e qualitativas (fenomenologia), com a finalidade de realizar a interação entre os métodos, fornecendo melhores possibilidades analíticas. Resultados: A taxa global de profilaxia de tromboembolismo venoso foi 70% e os pacientes clínicos apresentaram maior conformidade de prescrição de profilaxia em relação ao protocolo e a quantidade de fatores de risco/pacientes foi maior em pacientes clínicos em relação aos cirúrgicos. Os enfermeiros costumam preencher o protocolo no momento da admissão do paciente e, quando não conseguem, informam a necessidade durante passagem do plantão. Há um consenso entre os enfermeiros que médicos fixos nos setores prescrevem mais adequadamente a medicação profilática em relação aos rotativos. Conclusão: Para que todos os usuários se beneficiem da profilaxia, é necessária educação permanente/continuada associada a estratégias para envolvimento da equipe multiprofissional, além de divulgação maciça do protocolo de profilaxia de tromboembolismo venoso, a fim de diminuir as lacunas do conhecimento e instrumentalizar as equipe... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Objectives: To characterize the risk of venous thromboembolism and the use of prophylaxis in clinical and surgical patients, to evaluate a measure or non-compliance of prescribing medication prophylaxis and to develop nurses' perceptions regarding the use of venous prophylaxis protocol. Methods: Descriptive study with a multimedia approach or method, using quantitative (cross-sectional) and qualitative (phenomenology) techniques, using an interaction between methods, providing better analytical alternatives. Results: An overall rate of venous thromboembolism prophylaxis was 70% and clinical patients with a higher prevalence of prophylaxis prescription compared to the protocol and a number of risk factors / patients were the highest in clinical patients compared to physicians. Nurses usually complete the protocol at the time of patient admission and, when unable to do so, provide the necessary information during the passage of planting. There is a consensus among nurses that doctors fix in the prescribed sectors more that use prophylactic medication in relation to rotary ones. Conclusion: For all users who benefit from prophylaxis, it is mandatory / continued associated with multiprofessional team participation strategies, in addition to the massive dissemination of venous thromboembolism prophylaxis protocol, an end of loss as knowledge gaps and to instrumentalize as teams with the specific practice in using. / Doutor

La contraception hormonale combinée (CHC) est la contraception la plus utilisée en France. La maladie veineuse thromboembolique (MVTE), constitue le principal effet délétère de ces CHC. Des recommandations de bonnes pratiques sont publiées pour guider les prescripteurs. La meilleure compréhension des modifications biologiques associées aux différents types de CHC, les caractéristiques cliniques des femmes ayant eu une MVTE, la place de la recherche d’antécédents familiaux de MVTE (AFVTE) et d’une thrombophilie biologique avant la prescription d’une CHC constituent des pistes de recherche qui permettrait potentiellement d’optimiser la balance bénéfice-risque des CHC. Enfin l’impact de l’utilisation d’une contraception hormonale après un 1er épisode de MVTE reste peu évalué. Ce travail de thèse a été réalisé à la fois à l’aide de données biologiques d’utilisatrices de contraceptions hormonales (Etude EDGAR) et aussi à partir des données de l’étude de cohorte française COREVE (COntraception and REcurrent Venous Event). Cette étude a inclus 3121 femmes de moins de 45 ans au moment de leur 1er épisode de MVTE. Nous nous sommes particulièrement intéressés à l’analyse des caractéristiques de ces femmes en fonction du type de contraception utilisée, à la prévalence des facteurs de risque vasculaires et notamment les AFVTE. La fréquence d’épisode de MVTE associé à une prescription inadaptée de CHC, variait ainsi de 8.8 à 25.9 %. Par ailleurs, à l’aide d’une méthodologie de type cas versus cas, l’interaction entre l’utilisation d’une CHC et la présence d’une mutation du facteur V Leiden sur le risque de MVTE diffère significativement en fonction du progestatif combiné des CHC. / Combined hormonal contraception (CHC) is the most widely used contraception in France in which venous thrombosis embolism (VTE) is the main deleterious effect. Best practice recommendations are published in order to guide prescribers.The better understanding of the biological changes associated with different types of CHC, the clinical characteristics of women with VTE, the place of family history of VTE (FHVTE) and for biological thrombophilia before prescribing a CHC constitute research paths that could potentially optimize the risk-benefit balance of CHCs. Finally, the impact of hormonal contraception use after a first episode of VTE remains rarely evaluated.This work was carried out both using biological data from hormonal contraception users (EDGAR study) and also using data from the French cohort study COREVE (COntraception and REcurrent Venous Event).This study included 3121 women under 45 at the time of their 1st episode of VTE. We were particularly interested in analyzing the characteristics of these women according to the type of contraception used, the prevalence of vascular risk factors and especially the FHVTE.The frequency of VTE episode associated with an inadequate CHC prescription varied from 8.8 to 25.9%. Moreover, using a case-only methodology, the interaction between the use of CHC and the presence of a mutation of the factor V Leiden on the risk of VTE differs significantly depending on the progestin combined of the CHCs.

In Introduction, the author of this dissertation deals with postoperative venous thromboembolism (VTE), hereditary and acquired risk factors, prophylaxis regimens and recent recommendation of VTE prevention in surgery. In Practical part of this work the author assesses the risk of VTE in surgical patients according to risk assessment model. Genetic testing is carried out in all patients to determine the incidence of hereditary thrombophilia and coagulation markers are measured in 28-days postoperative period. Prevalence of VTE in 1-year postoperative period is observed. The results are analysed in group of patients with benign disease (hernia and gallstone disease) and group of patients with malignancy (colorectal cancer and pancreatic cancer) separately. The objective of this work is to determine the incidence of the most frequent thrombophilic mutations (factor V Leiden mutation and protrombin G20210A mutation) and assess the impact of hereditary thrombophilia on incidence of postoperative venous thromboembolism in general surgery. Validation of venous thrombosis risk assessment model recommended by Czech Society for Thrombosis and Hemostasis is further objective.