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.

Habilitacijos procedūrai teikiamoje mokslo darbų apžvalgoje apibendrinama Vilniaus universiteto Širdies ir kraujagyslių ligų klinikos Širdies chirurgijos centro patirtis, pakartotinai operuojant ligonius po širdies vožtuvų protezavimo. Įvertintas mažai trombogeniškų protezų efektyvumas. Nustatyta, kad labai sunkių ligonių su infekuotais protezais mirštamumas nemažėja, nors pastaraisiais metais daugiau operuojame III funkcinės klasės ligonių ir jų operacijų rezultatai puikūs. Dėl pasiūlyto radikalesnio triburio vožtuvo nesandarumo gydymo pirminių operacijų metu, efektyviai mažėja pakartotinių šio vožtuvo operacijų. Įteisinta planinė seno rutulinio protezo pakeitimo operacija. Įdiegti nauji širdies pjūviai, įdiegtos krūtinės ląstos pjūvių atlikimo metodikos, farmakologiniai ir nefarmakologiniai perioperacinio kraujavimo stabdymo būdai efektyviai sumažina kraujavimo pavojų. Pasiūlytas originalus kairio skilvelio drenavimo būdas per atskira torakotominį pjūvį padeda sumažinti pooperacinį širdies nepakankamumą. Šiame darbe remiuosi kartu su bendradarbiais atliktų operacijų rezultatais. Šiuo metu kaip skyriaus, kuriame gydomi ligoniai su vožtuvų patologija, vadovas atlieku daugiau kaip pusę pakartotinių operacijų. Moksliniai pranešimai apie pakartotinių operacijų rezultatus buvo daryti Lietuvos, Pasaulio ir Europos kongresuose ir suvažiavimuose. / The review of scientific work presented for habilitation procedure summarizes the experience of redo operations of patients after replacement of heart valves accumulated at the Heart Surgery Centre of Vilnius University Clinic of Angiology and Cardiology. The efficacy of low thrombogenicity valve prostheses was evaluated. It was found out that the mortality rate of very severely ill patients with infected did not decrease; however the larger number of patients in functional class III were being operated during the period of recent years and the results of these operations were excellent. The rate of redo tricuspid valve operations had decreased effectively because of more radical surgery treatment of this valve during the primary operation. The operation of replacement of old ball prosthesis has been validated. The new incisions of the heart were introduced as well as new methods of performance of chest box incisions and pharmacologic and non-pharmacologic methods of perioperative hemostasis; the methods mentioned above effectively reduced the risk of bleeding. The original method of the left ventricle venting via separate thoracotomy incision enabled to reduce postoperative heart failure. This work is based on the results of operations performed in cooperation with co-workers. As a chief of the department where the patients with pathology of heart valves are treated, I am performing more than a half of redo operations. The scientific presentations concerning the results of... [to full text]

INTRODUÇÃO: A fibrilação atrial (FA) é a arritmia cardíaca mais comum e está associada a uma significativa morbidade e mortalidade. A sua prevalência aumenta marcadamente com a idade. A terapia com anticoagulantes orais tem sido a base de tratamento e prevenção de eventos tromboembólicos em pacientes com FA. Entretanto, a anticoagulação oral em idosos pode ser desafiadora devido à vários fatores, como alterações orgânicas funcionais, risco aumentado de sangramento e eventos isquêmicos, presença de comorbidades, polifarmácia e uma menor aderência ao tratamento. OBJETIVOS: Avaliar a frequência de tromboembolismo e complicações hemorrágicas em pacientes muito idosos (idade >= 85 anos) em uso de varfarina; avaliar tempo na faixa terapêutica (TTR), causas do INR fora da faixa, escores de CHADS2 e CHA2DS2 - VASc, comorbidades associadas e causas de mortalidade. METODOS: análise retrospectiva de pacientes que iniciaram o tratamento com varfarina com uma idade >= 85 anos, entre abril de 1999 e setembro de 2013, controlados em uma clínica de anticoagulação oral. RESULTADOS: foram incluídos 164 pacientes; 51% eram do sexo masculino e a idade média de início e fim do tratamento com varfarina foram de 86,8 e 89,7 anos, respectivamente. A indicação mais comum para o uso de ACo foi a fibrilação atrial (86%). O seguimento médio foi de 34,6 ± 23 meses. O CHADS2 e CHA2DS2 - VASc médio dos pacientes foi 2,78 e 4,7, respectivamente. O tempo na faixa terapêutica (TTR) foi de 58,6%. A polifarmácia esteve presente em 78% dos pacientes. De acordo com as estimativas de Kaplan-Meier, a probabilidade livre de TE e sangramento grave foi de 93,5% e 90,5% em três anos, respectivamente. Quando analisados esses dois desfechos combinados, a probabilidade livre de tromboembolismo e sangramento grave foi de 83,4% em três anos. CONCLUSÃO: nesse estudo, o uso de um antagonista da vitamina k (varfarina) em pacientes com idade >= 85 anos esteve associado a um baixo risco de tromboembolismo e sangramento grave durante o período de seguimento. / INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated to a significant morbidity and mortality. Its prevalence strongly increases with aging. Therapy with oral anticoagulants (OAC) has been the basis of treatment and prevention of thromboembolic events in patients with AF. However, oral anticoagulation in the elderly can be challenging due to various factors such as the alteration of organic functions, greater risk of bleeding and ischemic events, presence of comorbidity, polypharmacy and a lower adherence to treatment. OBJECTIVES: Evaluate the frequency of thromboembolism and hemorrhagic complications in very elderly patients (aged >= 85 years) in use of warfarin; evaluate time in therapeutic range (TTR), causes of INR outside the range, scores of CHADS2 and CHA2DS2 - VASc, associated comorbidities and cause of death. METHODS: Retrospective analysis of patients who initiated treatment with warfarin at aged >=85 years, between April of 1999 and September of 2013, controlled in an oral anticoagulation clinic. RESULTS: A total of 164 patients were included in the study; 51% were males and the mean ages at the start and end of the treatment with warfarin were of 86,8 and 89,7 years, respectively. The most common indication for the use of OAC was atrial fibrillation (86%). The mean follow-up was of 34,6 ± 23 months. The mean CHADS2 and CHA2DS2 - VASc of patients was 2,78 and 4,7, respectively. The time in therapeutic range (TTR) was of 58,6%. Polypharmacy was present in 78% of patients. According to the Kaplan-Meier estimates, the survival curve of TE and severe bleeding was of 93,5% and 90,5% in three years, respectively. When these two combined outcomes are analyzed, the survival curve of thromboembolism and severe bleeding was of 83,4% in three years. CONCLUSION: In this study, the use of one vitamin K antagonist (warfarin) in patients aged >= 85 years was associated to a low risk of thromboembolism and severe bleeding during the follow-up period.

Hypercoagulable states occur when the process of hemostasis is disturbed. It manifests as a deep vein thrombosis or a pulmonary embolism. It is also one of the most common cardiovascular diseases. There are two factors- genetic and acquired. Inherent factors involve coagulation inhibitor deficiency, prothrombin gene mutation and activated protein C resistance. Acquired factors include antiphospolipid syndrome, pregnancy, overweight etc. The analytic part of the thesis is focused on the effect of a low molecular weight heparin. It was shown in many theses that the LMWH could have a negative impact on a parturition complications or a week of parturition, a birth weight. The results of statistical analysis show that there is a coherence between the week of parturition and the type of parturition. What is more, the anticoagulation drug therapy shows a positive effect on the week of parturion. The data used in the thesis originate in laboratory information management system of Clinical Haematology ward in the hospital Nemocnice České Budějovice a.s.

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.

INTRODUÇÃO: A fibrilação atrial (FA) é a arritmia cardíaca mais comum e está associada a uma significativa morbidade e mortalidade. A sua prevalência aumenta marcadamente com a idade. A terapia com anticoagulantes orais tem sido a base de tratamento e prevenção de eventos tromboembólicos em pacientes com FA. Entretanto, a anticoagulação oral em idosos pode ser desafiadora devido à vários fatores, como alterações orgânicas funcionais, risco aumentado de sangramento e eventos isquêmicos, presença de comorbidades, polifarmácia e uma menor aderência ao tratamento. OBJETIVOS: Avaliar a frequência de tromboembolismo e complicações hemorrágicas em pacientes muito idosos (idade >= 85 anos) em uso de varfarina; avaliar tempo na faixa terapêutica (TTR), causas do INR fora da faixa, escores de CHADS2 e CHA2DS2 - VASc, comorbidades associadas e causas de mortalidade. METODOS: análise retrospectiva de pacientes que iniciaram o tratamento com varfarina com uma idade >= 85 anos, entre abril de 1999 e setembro de 2013, controlados em uma clínica de anticoagulação oral. RESULTADOS: foram incluídos 164 pacientes; 51% eram do sexo masculino e a idade média de início e fim do tratamento com varfarina foram de 86,8 e 89,7 anos, respectivamente. A indicação mais comum para o uso de ACo foi a fibrilação atrial (86%). O seguimento médio foi de 34,6 ± 23 meses. O CHADS2 e CHA2DS2 - VASc médio dos pacientes foi 2,78 e 4,7, respectivamente. O tempo na faixa terapêutica (TTR) foi de 58,6%. A polifarmácia esteve presente em 78% dos pacientes. De acordo com as estimativas de Kaplan-Meier, a probabilidade livre de TE e sangramento grave foi de 93,5% e 90,5% em três anos, respectivamente. Quando analisados esses dois desfechos combinados, a probabilidade livre de tromboembolismo e sangramento grave foi de 83,4% em três anos. CONCLUSÃO: nesse estudo, o uso de um antagonista da vitamina k (varfarina) em pacientes com idade >= 85 anos esteve associado a um baixo risco de tromboembolismo e sangramento grave durante o período de seguimento. / INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated to a significant morbidity and mortality. Its prevalence strongly increases with aging. Therapy with oral anticoagulants (OAC) has been the basis of treatment and prevention of thromboembolic events in patients with AF. However, oral anticoagulation in the elderly can be challenging due to various factors such as the alteration of organic functions, greater risk of bleeding and ischemic events, presence of comorbidity, polypharmacy and a lower adherence to treatment. OBJECTIVES: Evaluate the frequency of thromboembolism and hemorrhagic complications in very elderly patients (aged >= 85 years) in use of warfarin; evaluate time in therapeutic range (TTR), causes of INR outside the range, scores of CHADS2 and CHA2DS2 - VASc, associated comorbidities and cause of death. METHODS: Retrospective analysis of patients who initiated treatment with warfarin at aged >=85 years, between April of 1999 and September of 2013, controlled in an oral anticoagulation clinic. RESULTS: A total of 164 patients were included in the study; 51% were males and the mean ages at the start and end of the treatment with warfarin were of 86,8 and 89,7 years, respectively. The most common indication for the use of OAC was atrial fibrillation (86%). The mean follow-up was of 34,6 ± 23 months. The mean CHADS2 and CHA2DS2 - VASc of patients was 2,78 and 4,7, respectively. The time in therapeutic range (TTR) was of 58,6%. Polypharmacy was present in 78% of patients. According to the Kaplan-Meier estimates, the survival curve of TE and severe bleeding was of 93,5% and 90,5% in three years, respectively. When these two combined outcomes are analyzed, the survival curve of thromboembolism and severe bleeding was of 83,4% in three years. CONCLUSION: In this study, the use of one vitamin K antagonist (warfarin) in patients aged >= 85 years was associated to a low risk of thromboembolism and severe bleeding during the follow-up period.

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.

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.