Thesis (M.S.)--Florida State University, 2004. / Advisor: Dr. Jeanne Flannery, Florida State University, School of Nursing. Title and description from dissertation home page (viewed Sept. 28, 2004). Includes bibliographical references.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfilment of the requirements for the degree of Master of Pharmacy Johannesburg 2001. i / The use of a low molecular weight heparin, enoxaparin was evaluated in the prevention and treatment of deep vein thrombosis. Patterns of use were analysed and measured against pre-determined criteria with a view to promoting optimal use and identifying those factors, which may contribute to safer use of the drug. / IT2018

5 ABSTRACT Background: Thromboembolic disease is one of the most common causes of pregnant women morbidity and mortality. The pregnancy period is often the first time, when the apparent congenital or acquired thrombophilia is identi- fied. Patients with thrombophilia have an increased risk of pregnancy compli- cations. The optimal anticoagulant prophylaxis helps to prevent these compli- cations. Methods: The presented work is focused on monitoring of coagulation param- eters, blood counts and acute phase proteins in pregnant women (N = 68) with thrombophilia treated with enoxaparin during pregnancy and it is also con- cerned with evaluation of effectiveness of anticoagulant therapy during preg- nancy using anti FXa activity determination based on inhibition of FXa weight, coagulation parameters and acute phase proteins. In the first and the second part of the study, there is no control group of pregnant patients with severe thrombophilia, but no anticoagulation - this is justified by ethical rea- sons. In the third part, we examined by questionnaire our patients for enoxap- arin adverse reactions at the injection site. Finally, the last part is focused on evaluation of enoxaparin effects on bone remodelling markers, compared with a group of pregnant women without anticoagulation. Results: During the...

Orientador: Joyce Maria Anicchino-Bizzacchi / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-22T13:12:37Z (GMT). No. of bitstreams: 1 Huber_StephanyCares_M.pdf: 5877456 bytes, checksum: 79a59ae5e01aa03f9d5a57ca56e58df7 (MD5) Previous issue date: 2013 / Resumo poderá ser visualizado no texto completo da tese digital / Abstract is available with the full electronic document / Mestrado / Clinica Medica / Mestra em Clínica Médica

Orientador: Joyce Maria Annichino-Bizzacchi / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-23T22:14:32Z (GMT). No. of bitstreams: 1 Prado_LucasBessa_M.pdf: 3008068 bytes, checksum: 3758f8a952dfe1f77c113246b8e2a0bd (MD5) Previous issue date: 2013 / Resumo: A Trombose Venosa Profunda (TVP) é definida como uma oclusão parcial ou total da circulação venosa profunda. A heparina é um fármaco com ação anticoagulante e antitrombótica utilizado desde 1930. O custo, a via de administração (endovenosa ou subcutânea) e as doses repetidas são algumas das limitações do seu uso. Assim, o desenvolvimento de um produto que possa ser administrado por via subcutânea ou oral em um menor número de aplicações, torna-se um importante desafio e de grande aplicabilidade clínica. Sistemas de liberação sustentada permitem que o fármaco seja encapsulado e liberado gradativamente. Este estudo constituiu na preparação, caracterização e avaliação in vivo de nanopartículas de poli (?-caprolactona) (PCL) e quitosana como carreadores de heparina de baixo peso molecular (enoxaparina). As nanopartículas foram preparadas pelo método de dupla emulsão água/óleo/água e evaporação do solvente. A caracterização das nanopartículas foi realizada por microscopia eletrônica de varredura (MEV), onde foram observadas partículas esféricas e homogêneas. O diâmetro médio das nanopartículas foi de 512,8 ± 13,8 nm e o potencial zeta foi de +30,9 ± 1,3 mV. A eficiência de encapsulamento, analisada pelo método Azure II foi de 99,04 ± 0,001 %. A atividade anticoagulante in vivo da enoxaparina encapsulada foi avaliada pela atividade anti-Xa plasmática, através de método colorimétrico. Quando a enoxaparina livre foi administrada por via subcutânea observou-se um pico de atividade (0,5 UI/mL) em 1 hora, com um decréscimo gradual até 6 horas. A atividade anticoagulante da enoxaparina encapsulada em nanopartículas manteve-se por até 14 horas, quando foi administrada por via subcutânea, sugerindo que as nanopartículas podem permitir que a enoxaparina seja liberada de forma gradual, podendo ser uma vantagem na prática clínica. Após a administração das nanopartículas por via oral não se observou nenhuma atividade em até 14 horas, sugerindo que as nanopartículas não tenham sido absorvidas ou a enoxaparina tenha sido degradada no trato gastrointestinal. Para avaliação do efeito antitrombótico foi padronizado o modelo de TVP por estase e hipercoagulabilidade em ratos. Após administração subcutânea, houve uma significativa diminuição do tamanho do trombo formado tanto com o emprego de enoxaparina livre (p= 0,002) como após encapsulamento em nanopartículas (p= 0,0411) em comparação ao grupo controle. Quando foram administradas nanopartículas por via oral, os resultados mostraram que não houve diferença estatística em comparação ao grupo controle (p= 0,9476) e a um grupo de nanopartículas vazias (p= 0,9372). Em resumo, o método de dupla emulsão a/o/a mostrou-se eficiente para o encapsulamento de enoxaparina, proporcionando a obtenção de nanopartículas esféricas e com alta eficiência de encapsulamento. Pelos estudos in vivo, a enoxaparina encapsulada mostrou uma atividade anticoagulante com liberação sustentada, por um período superior ao obtido com a enoxaparina livre, com excelente efeito antitrombótico quando administrada por via subcutânea. Contudo, não se observou nenhum efeito anticoagulante ou antitrombótico quando as nanopartículas foram administradas por via oral. Novos experimentos com quitosanas de diferentes massas molares serão necessários na tentativa de possibilitar a absorção oral dessas nanopartículas / Abstract: Deep vein thrombosis (DVT) is defined as partial or total occlusion of the deep venous circulation. Heparin is a drug with anticoagulant and antithrombotic action used since 1930. The costs, administration vias (intravenous or subcutaneous) and the repeated doses are some limitations of its use. Thus, the development of a product that could be administered subcutaneous or orally in a smaller number of applications becomes a major challenge with huge clinical applicability. Sustained release systems allow the medication to be gradually encapsulated and released. This study was based on the preparation, characterization and in vivo evaluation of nanoparticles of poly (?-caprolactone) (PCL) and chitosan as carriers of low molecular weight heparin (enoxaparin). The nanoparticles were prepared by the double emulsion water/oil/water method and solvent evaporation. The nanoparticles characterization was performed by scanning electron microscopy (SEM), in which were observed spherical and homogeneous particles. The average diameter of the nanoparticles was 512.8 ± 13.8 nm and the zeta potential was +30.9 ± 1.3 mV. The encapsulation efficiency, analyzed by Azure II method, was 99.04 ± 0.001%. The in vivo anticoagulant activity of the encapsulated enoxaparin was evaluated by plasmatic anti-Xa activity performed by colorimetric method. When the free enoxaparin was subcutaneously administered a peak of activity was observed (0.5 IU/mL) in 1 hour with a gradual decrease until 6 hours. The anticoagulant activity of the nanoparticles encapsulated enoxaparin was kept until 14 hours when it was administered subcutaneously, suggesting that nanoparticles may allow the enoxaparin release by a gradual way, what could be an advantage on clinical practice. After the oral administration of the nanoparticles, any activity could be observed in until 14 hours, suggesting that or the nanoparticles might be not absorbed or the enoxaparin might be degraded on the gastrointestinal tract. In order to evaluate its antithrombotic effect, it was standardized a model of DVT by stasis and hypercoagulability in rats. After subcutaneous administration, there was a significative reduction on the thrombus size both with free enoxaparin (p= 0.002) and after encapsulation (p= 0.0411) in comparison with control group. When nanoparticles were administered orally, the results showed no statistical difference compared to the control group (p = 0.9476) and to a group of empty nanoparticles (p = 0.9372). In summary, the double emulsion method w/o/w was efficient for the enoxaparin encapsulation, providing the obtainment of spherical nanoparticles with high encapsulation efficiency. For in vivo studies, the encapsulated enoxaparin showed a sustained release anticoagulant activity for a higher period than that obtained with free enoxaparin, with an excellent antithrombotic effect when administered subcutaneously. However, there was no anticoagulant or antithrombotic effect when the nanoparticles were administered orally. Further experiments with chitosans of different molecular weights will be needed on the attempt to allow the oral absorption of these nanoparticles / Mestrado / Medicina Experimental / Mestre em Fisiopatologia Médica

5 ABSTRACT Background: Thromboembolic disease is one of the most common causes of pregnant women morbidity and mortality. The pregnancy period is often the first time, when the apparent congenital or acquired thrombophilia is identi- fied. Patients with thrombophilia have an increased risk of pregnancy compli- cations. The optimal anticoagulant prophylaxis helps to prevent these compli- cations. Methods: The presented work is focused on monitoring of coagulation param- eters, blood counts and acute phase proteins in pregnant women (N = 68) with thrombophilia treated with enoxaparin during pregnancy and it is also con- cerned with evaluation of effectiveness of anticoagulant therapy during preg- nancy using anti FXa activity determination based on inhibition of FXa weight, coagulation parameters and acute phase proteins. In the first and the second part of the study, there is no control group of pregnant patients with severe thrombophilia, but no anticoagulation - this is justified by ethical rea- sons. In the third part, we examined by questionnaire our patients for enoxap- arin adverse reactions at the injection site. Finally, the last part is focused on evaluation of enoxaparin effects on bone remodelling markers, compared with a group of pregnant women without anticoagulation. Results: During the...

Parenteral anticoagulants are vital in the prevention of thrombus formation and thus, are commonly used in a hospital setting. A thrombus can restrict blood flow where formed such is the case with deep vein thrombosis (DVT). They may also become dislodged forming an emboli, which may travel and become lodged in the lungs, causing a pulmonary emboli, or other vessels including those going to the brain, causing a stroke. While anticoagulants are many times necessary, when given subcutaneously, they have been associated with pain, purpura, melena, hematuria, osteoporosis, thrombocytopenia, and hematoma formation. While hematoma formation has not proven to be life threatening, it does lead to increased patient discomfort, distorted body image, and may lead to surgery. Different methods of preventing hematoma formation have been studied with regards to anticoagulant injection technique though no method has been consistently substantiated by the research or adopted by nursing texts.

Enoxaparin, a low-molecular-weight heparin, is commonly used as an anticoagulant in dogs, and is currently dosed at 0.8mg/kg every 6 hours. With an increase in individual enoxaparin doses, less frequent dosing may be possible, thereby reducing owner inconvenience and expense. The three phases of this study investigated the appropriate dose (Phase one- 0.8mg/kg, SQ once; Phase two- 2mg/kg, SQ once; Phase three- 1.3 mg/kg, SQ q8h for 7 total doses) and dosing interval needed for maximum effectiveness of enoxaparin. A Sonoclot® analyzer and factor Xa activity were used to assess level of anticoagulation in six healthy dogs. Anticoagulation was inconsistent at the 0.8mg/kg dose, while the 2mg/kg dose showed a high level of anticoagulation, and the 1.3mg/kg dose provided more reliable anticoagulation than the other dosages and dosing intervals. Small sample size and the use of same-breed healthy dogs potentially affected the strength of the results.

Class of 2017 Abstract / Objectives: The first aim is to assess efficacy of aspirin versus enoxaparin in preventing a venous thromboembolism (VTE) after a total knee arthroplasty (TKA) or total hip arthroplasty (THA) within 30 days after discharge. The second aim is to assess the safety of aspirin versus enoxaparin in preventing major bleeding events after a TKA or THA within 30 days after discharge. Methods: This study was a retrospective cohort study with data obtained from an online Veterans Affairs (VA) hospital database. For analysis, the primary outcome was assessed with a Chi-Square test, and the secondary outcome was reported with descriptive statistics.Results: Results: Demographics for 374 patients (TKA, n = 275; THA, n = 99): 90% male, average age of 65, average body mass index (BMI) of 32, 26% smokers, 72% had a history of hypertension, and 60% had a history of dyslipidemia. VTE events 30 days post-operatively: enoxaparin (n = 2), enoxaparin/aspirin (n = 1), and aspirin (n = 2) (P-value = 0.78). Safety events (major bleeding events): enoxaparin (n = 42), enoxaparin/aspirin (n = 7), and aspirin (n = 4). Conclusions: There was no significant difference between the treatment groups for VTE rate 30 days post- operation. The enoxaparin treatment group had the greatest number of safety events compared to the other groups.

Introdução: A interação entre os anticoagulantes e a agregabilidade plaquetária é complexa. Dados laboratoriais prévios mostraram que a dabigatrana aumenta a excreção urinária de metabólito do tromboxano, indicando efeito de ativação de plaquetas. Posteriormente, dados do estudo RELY sugeriram que a dabigatrana 150mg poderia aumentar o risco de infarto do miocárdio em pacientes com fibrilação atrial. Objetivos: Comparar a influência da Dabigatrana e Enoxaparina na agregabilidade plaquetária. Métodos: Estudo prospectivo, intervencionista, realizado em pacientes com doença arterial coronariana (DAC) crônica em uso de aspirina em baixas doses. Os indivíduos foram inicialmente designados para dabigatrana 150mg, 2x/dia, por 5 dias, seguido por um período de washout de 30 dias e depois para exoxaparina 1mg/kg, 2x/dia, por um período adicional de 5 dias. Os testes de função plaquetária foram realizados no início e após cada fase de intervenção, usando agregometria de sangue total p (MEA) (objetivo primário), ELISA para determinação quantitativa de tromboxano B2 (TXB2), Verify Now Aspirin e testes de coagulação (objetivos secundários). Resultados: Em comparação com os valores basais, a dabigatrana aumentou a agregabilidade plaquetária avaliada pelo teste MEA-ASPI (+5U ± 24,1), enquanto a enoxaparina diminuiu a agregabilidade plaquetária (-6U ± 22,2), p=0,012 para a comparação entre os grupos ). O mesmo padrão foi observado usando o ensaio TXB2 (+2pg/mL para dabigatrana, -13pg/mL para enoxaparina, p = 0,011). Não houve diferenças significativas entre os dois grupos em relação aos demais testes. Individualmente, a enoxaparina diminuiu significativamente a agregabilidade plaquetária por TXB2 [33 (16,5 - 95)pg/mL vs. 20 (10-52) pg/mL, respectivamente, p = 0,026), mas não foram observadas diferenças significativas individuais com a dabigatrana em relação aos valores basais. Conclusões: Em relação à agregabilidade plaquetária, há um efeito oposto significativo da dabigatrana (aumento) em comparação com a enoxaparina (diminuição). Individualmente, foi observada uma diminuição significativa na agregabilidade plaquetária apenas com a enoxaparina, quando comparada com valores basais / Background: The interaction between anticoagulants and platelet aggregation is complex. Previous laboratory data have shown that dabigatran increases urinary thromboxane metabolite excretion, indicating platelet-activating effect. Thereafter, data from RELY trial suggested that dabigatran 150mg could enhance the risk of myocardial infarction in atrial fibrillation patients. Objectives: To compare the influence of Dabigatran and Enoxaparin on platelet aggregation. Methods: Prospective, interventional study conducted in chronic coronary artery disease (CAD) patients taking low-dose aspirin. Subjects were assigned initially to dabigatran 150mg bid for 5 days followed by a washout period of 30 days and then to exoxaparin 1mg/kg bid for an additional 5 days period. Platelet function tests were performed at baseline and after each intervention phase using multiple electrode aggregometry (MEA) (primary endpoint), ELISA for plasma quantitative determination of thromboxane B2, Verify Now Aspirin and coagulation tests as secondary endpoints. Results: In comparison with the baseline values, dabigatran increased platelet aggregation evaluated by MEAASPI test (+5U ± 24.1), whereas enoxaparin decreased platelet aggregation (- 6U± 22.2), p=0.012 for the comparison between the groups). The same pattern was observed using theTxB2 assay (+2pg/mL for dabigatran, -13pg/mL for enoxaparin, p=0.011). There were no significant differences between both groups regarding the VerifyNow Aspirin or the other platelet function and coagulation tests utilized. Individually, enoxaparin significantly decreased platelet aggregation by TXB2 [33 (16,5 - 95) pg/mL vs. 20 (10-52) pg/mL, respectivamente, p = 0.026) but no significant differences were observed with dabigatran when individually compared to baseline. Conclusions: Regarding platelet aggregation, there is a significant opposite effect of dabigatran (increase) in comparison with enoxaparin (decrease). Individually, a significant decrease in platelet aggrebability was observed with enoxaparin, but no significant differences were observed with dabigatran