Made available in DSpace on 2014-06-11T19:31:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2002Bitstream added on 2014-06-13T21:02:14Z : No. of bitstreams: 1 padovan_lem_dr_araca_prot.pdf: 3510431 bytes, checksum: bd99311cc553fdbabfb1f0575b0b70ce (MD5) / Este estudo avaluoi-se o proceso de reparo de feridas de extração dental após irrigação com solução a 5% de ácido epsilon-amino-capróico (EACA) e implante de adesivo fibrínico (Tissucol). Foram utilizados 60 ratos (Wistar), machos, com peso entre 250 gramas e 300 gramas e divididos em 03 grupos com 20 animais cada, onde foram realizados os seguintes procedimentos: No grupo 1 foi administrado 0,1 ml/100mg de peso corporal de solução salina a 0,9%, iniciando-se 06 dias antes da exodontia, administração diária de 0,03ml de varfarina sódica sendo mantida durante todo o experimento. Após a exodontia do incisivo superior direito, seus alvêolos foram preenchido com adesivo fibrinico, No grupo III, os animais desse grupo receberam os mesmos procedimentos dos animais do grupo IIe, após a exodontia, tiveram seus alvêolos irrigados com 5ml de solução a 5% de ácido epsilon-amino-capróico e também preenchidos com adesivos fibrinico (Tissucol)...

Introdução: A varfarina é um dos anticoagulantes orais (ACO) mais utilizados na atenção primária a saúde. Com janela terapêutica estreita, exibe grande variabilidade de resposta farmacológica, e maior suscetibilidade de eventos adversos, como sangramentos e tromboembolismo venoso. Entre os fatores que influenciam na variabilidade de dose destaca-se as interações tanto com medicamentos, como com a dieta e o polimorfismo genético. Objetivos: Estimar a incidência de eventos adversos relacionados ao uso de varfarina e descrever o itinerário do usuário pelo sistema público de saúde para resolução dos problemas. Métodos: trata-se de uma coorte prospectiva realizada por um período de 18 meses com usuários do serviço público de saúde, em uso de varfarina, do município de Ijuí/RS. Os dados foram coletados por entrevistas mensais nas residências e complementados com informações médicas obtidas na atenção primária e terciária. As interações medicamentosas foram checadas em bases de dados e os hábitos alimentares conforme metodologia validada. A estatística utilizada para associar sangramento e Time in Therapeutic Range (TTR) e os fatores de risco foi teste de Poison. O projeto foi aprovado no Comitê de Ética em Pesquisa da UFRGS, com parecer número 336.259/2013. Resultados: Foram entrevistados e acompanhados 69 pacientes, sendo que 64 concluíram o acompanhamento e 5 faleceram durante o estudo, 55,1% eram do sexo feminino, com idade média de 64,3 ±13,7 anos. O tempo médio de uso de varfarina foi de 5,5 anos, a dose média semanal foi de 30,69±15,19mg e o principal motivo para uso de varfarina foi prótese valvular (39,7%). A média de medicamentos utilizados por usuário foi de 9,6±4,5. Quanto aos eventos, os sangramentos tiveram incidência de 37,7/100 pacientes/ano, o tromboembolismo de 4,8/100 pacientes/ano e de óbitos de 4,8/100 pacientes/ano. Os sangramentos apresentaram associação com possuir mais que três interações medicamentosas com a varfarina (p=0,048) e com uso de medicamentos por automedicação (p=0,030). Já para o TTR houve associação com a idade inferior a 65 anos (p=0,032). E 67 usuários estavam suscetíveis a interações medicamentosasas com varfarina, com predomínio das moderadas, sendo a média de interações com este medicamento de 2,91±1,52. A maioria das interações agiam sobre o efeito anticoagulante da varfarina, aumentando a probabilidade de sangramento. Entre as interações que os usuários apresentavam, no momento do sangramento, as mais frequentes foram com: omeprazol, sinvastatina e paracetamol. A maioria dos entrevistados apresentou consumo baixo de vitamina K. Verificou-se que sangramentos e tromboembolismos venosos foram mais frequentes nos pacientes em início de tratamento. E todos os pacientes que foram a óbito durante o acompanhamento (5) eram pacientes com mais de um ano de uso de varfarina. Para a resolução de eventos adversos na maioria dos casos o paciente realizou cuidado domiciliar (53,4%), seguido por busca pela Unidades Básicas de Saúde, 7 pacientes buscaram o serviço de emergência e 5 realizaram internação hospitalar. Observou-se que aproximadamente metade dos pacientes não mostrou seus exames de INR (Razão Normalizada Internacional) ao médico. E na falta de varfarina na rede pública de saúde do município, que ocorreu entre os meses 13 e 16, entre 24,9 a 43,5%, deixaram de usar o medicamento. Os resultados do polimorfismo demonstram que 47 (71,2%) não apresentam polimorfismo ao genótipo CYP2C9, e 24 (36,4%) ao genótipo VKORC1. Avaliando os dois genótipos associados, verifica-se que 17 (25,8%) não apresentam polimorfismo a nenhum destes. Não foi observada associação estatística do polimorfismo com sexo e raça. Observou-se diferença significativa entre a dose utilizada para os diferentes polimorfismos (p=0,013). Da mesma forma, para o VKORC1, houve diferença significativa entre a dose e o genótipo (p=0,018). Conclusão: Estes resultados demonstram a necessidade de uma maior assistência a estes pacientes, buscando melhores resultados clínicos, com menos eventos adversos. / Introduction: Warfarin is an oral anticoagulant (OAC) most used in primary health care. With narrow therapeutic window, shows great variability in drug response, and greater susceptibility to adverse events such as bleeding and venous thromboembolism. Among the factors that influence the amount of variability highlights the interactions with both drugs, as with diet and genetic polymorphism. Objectives: To estimate the incidence of adverse events related to warfarin use and describe the user journey through the public health system to the problems. Methods: This is a prospective cohort study conducted over a period of 18 months with users of the public health service in the use of warfarin, the city of Ijuí/RS. The data were collected monthly interviews in homes and complemented with medical information obtained in primary and tertiary care. Drug interactions were checked in databases and eating habits as validated methodology. The statistics used to associate bleeding and Time in Therapeutic Range (TTR) and the risk factors was Poison test. The project was approved by the Research Ethics Committee of UFRGS, with opinion number 336259/2013. Results: We interviewed and followed 69 patients, 64 completed the follow-up and 5 died during the study, 55.1% were female, mean age 64.3 ± 13.7 years. The mean duration of warfarin use was 5.5 years, the average weekly dose was 30.69 ± 15,19mg and the main reason for warfarin use was valvular prosthesis (39.7%). The average per user used medications was 9.6 ± 4.5. As for events, the bleeding had incidence of 37.7 / 100 patients / year, thromboembolism of 4.8 / 100 patients / year and deaths of 4.8 / 100 patients / year. Bleeds were associated with having more than three drug interactions with warfarin (p = 0.048) and use of self-medication by drugs (p = 0.030). As for the TTR was no association with age less than 65 years (p = 0.032). And 67 users were susceptible to medicamentosasas interactions with warfarin, with a predominance of moderate, with an average of interactions with this drug of 2.91 ± 1.52. Most interactions acting on the anticoagulant effect of warfarin, increasing the probability of bleeding. Among the interactions that users had, at the time of bleeding, the most common were with: omeprazole, simvastatin and acetaminophen. Most respondents showed low consumption of vitamin K. It was found that bleeding and venous thromboembolism were more frequent in patients starting treatment. And all patients who died during follow-up (5) were patients with more than one year of warfarin use. For adverse event resolution in most cases the patient underwent home care (53.4%), followed by search for the Basic Health Units, 7 patients sought emergency services and 5 held hospitalization. It was observed that approximately half of the patients showed their INR test (International Normalized Ratio) to the doctor. And in the absence of warfarin in public municipal health, which occurred between the months 13:16, from 24.9 to 43.5% stopped using the drug. The polymorphism results demonstrate that 47 (71.2%) did not have the polymorphism CYP2C9 genotype, and 24 (36.4%) the VKORC1 genotype. Evaluating the two genotypes associated, it is found that 17 (25.8%) did not show any polymorphism thereof. There was no statistical association of the polymorphism with gender and race. A significant difference between the dose for different polymorphisms (p = 0.013). Likewise, for the VKORC1, a significant difference between the dose and genotype (p = 0.018). Conclusion: These results demonstrate the need for further assistance to these patients, looking for better clinical outcomes, with fewer adverse events.

No description available.

Please read the abstract in the section 00front of this document / Dissertation (MSc (Chemical Pathology))--University of Pretoria, 2005. / Chemical Pathology / unrestricted

Vitamin K Antagonists [VKA] are the most frequently used oral anticoagulants in clinical practice; however, many patients fail to achieve adequate anticoagulation control. We conducted a randomized, placebo controlled, double blind study of Vitamin K1 (200mcg per day, Swanson Vitamins) in a population with predominantly venous thromboembolism aimed at evaluating its effectiveness in improving anticoagulation control in unstable patients. This study also aimed to evaluate the impact that clinical variables, patient anticoagulation knowledge, and genetic polymorphisms in genes known to impact warfarin and Vitamin K metabolism [VKORC1, CYP4F2, CYP2C9] had on anticoagulation control and intervention effectiveness. A total of N=54 patients were enrolled in the study over 15 months [January 2009 to June 2010]. Change score analysis and multivariate linear regression modelling of anticoagulation control measures were performed. No statistically significant reduction was observed in the Vitamin K1 arm for percent time in therapeutic range; however, reduction was observed in standard deviation of INRs [Change Score Vitamin K = -0.259, p=0.0261; Regression Model 95% C.I Beta Vitamin K = 0.38 to -0.08] during the intervention period. Adjusting for treatment group allocation, independent predictors of increased INR standard deviation included: >5 alcoholic drinks per week [95% C.I Beta = 0.04 to 0.41], self-reported dosing errors [95% C.I Beta = 0.13 to 0.47], and missed INR appointments [95% C.I Beta = 0.002 to 0.05]

Statement of the problem: The risk-benefit profile of warfarin anticoagulation in hemodialysis (HD) patients differs compared to the non-HD population. Computerized decision support systems (CDSS) to assist with anticoagulation management are safe and effective in the non-HD population but had not previously been studied in HD outpatients. Methods of investigation: A before – after study compared anticoagulation control during pre-existing, nephrologist-led anticoagulation management to that following implementation of a pharmacist-led, CDSS-assisted strategy, in HD patients on warfarin at The Ottawa Hospital. Results: Forty-two patients were included. Following implementation of the CDSS-assisted strategy, median time-in-range increased by 3.7% (IQR, -9.5% - 20.6%; p = 0.247). Median frequency of INR tests per day decreased: -0.040 (IQR, -0.074 to –0.0008; P = 0.0001). Adverse events were similar. Conclusion: A CDSS-assisted strategy for anticoagulation management in HD patients is effective, safe and may lead to cost savings related to less frequent INR testing.

Calciphylaxis is a late complication of end-stage renal disease (ESRD) affecting ~1–4% patients on hemodialysis, with a mortality rate of >50%. Cutaneous manifestations include necrotic, non-healing ulcers most commonly in the lower extremities. Visceral organ vasculopathy often occurs as well. Warfarin is a possible risk factor due to its effect on the inhibition of Matrix GLa protein. Under the influence of hyperphosphatemia, vascular smooth muscle cells can undergo ectopic calcification in absence of the MGLa protein. The issue of anticoagulation in dialysis patients has therefore been debated, as Warfarin may potentially induce vasculopathy and increase risk of bleeding, such as hemorrhagic strokes and GI bleeds. A 64-year-old male with ESRD, non-compliant with dialysis, presented with lower extremity pain. Patient was noted to have large, malodorous, bilateral lower extremity ulcers with necrosis and eschars. Punch biopsy of the ulcers demonstrated acute inflammation with calcium deposits and thrombi within the blood vessels, suggestive of Calciphylaxis. Patient was started on Sodium Thiosulfate and Sevelamer for hyperphosphatemia. Atrial fibrillation was incidentally found on EKG, and due to high risk of stroke based on the CHA2DS-VASc score, patient was started on Heparin and bridged to Warfarin on discharge. Patient was readmitted 3 months later to the ICU with septic shock. Lower extremity ulcers appeared to be healing, but he reported several episodes of hematochezia (INR=2.0, hemoglobin=5.2). Warfarin was therefore held and patient was transfused. EGD showed no evidence of upper GI bleed, however patient refused colonoscopy. Patients on dialysis are at increased risk of bleeding due to defective primary hemostasis. The most serious source of bleeding is gastrointestinal, which accounts for 3–7% of all deaths in the dialysis population. Current guidelines for management of atrial fibrillation by the American Heart Association recommend warfarin for oral anticoagulation in patients with ESRD who have a CHA2DS2-VASc score of 2 or greater to prevent thromboembolic events. Our patient with ESRD and Calciphylaxis presented with new-onset atrial fibrillation and therefore started on Warfarin due to high CHA2DS2-VASc score. However patient developed a GI bleed with worsening anemia requiring transfusion, prompting discontinuation of Warfarin. It is therefore questionable whether the risk-benefit assessment based on CHA2DS2-VASc is appropriate for dialysis patients. Unfortunately, all the data available on the subject of Warfarin in ESRD patients are observational without any randomized-clinical trials. Therefore no objective criteria exist to modify the anticoagulation guidelines in dialysis patients.

Objective: To document maternal and foetal morbidity and mortality in anticoagulated, pregnant patients with mechanical heart valves until 42 days postpartum. Methods: In a tertiary single-centre, prospective cohort, 178 consecutive patients at the cardiac-obstetric clinic were screened for warfarin use between 1 July 2010 and 31 December 2015. Of 33 pregnancies identified, 29 were included. Patients received intravenous unfractionated heparin from six to 12 weeks’ gestation and peripartum, and warfarin from 12 to 36 weeks. Maternal outcomes including death, major haemorrhage and thrombosis, and foetal outcomes were documented. Results: There were two maternal deaths, five returns to theatre post-delivery, eight patients transfused, six major haemorrhages, one case of infective endocarditis and three ischaemic strokes. Ten pregnancies had poor foetal outcomes (six miscarriages, three terminations, one early neonatal death). Twenty patients required more than 30 days’ hospitalisation, and 15 required three or more admissions. HIV positivity was associated with surgical delivery (p = 0.0017). Conclusions: Complication rates were high despite centralized care.

No description available.

Warfarin är ett läkemedel som används för att förhindra att högriskpatienter såsom de med förmaksflimmer får tromboembolism. Denna verkan uppnås genom att hämma de K-vitaminberoende faktorerna VII, X och protrombin och på så sätt minska blodets förmåga att koagulera. Att hitta rätt dosering av läkemedlet för warfarinbehandlade patienter har visat sig vara svårt eftersom det kräver regelbunden provtagning och påverkas av mat- och levnadsvanor. Det vanligaste sättet att mäta protrombinkomplexhalten är med venös plasma men det är även möjligt att använda sig av kapillär plasma. Helblod kan användas för mekaniska metoder som inte använder sig av optisk detektion. Fördelen är att helblod inte kräver centrifugering. Studiens syfte var att undersöka om det fanns en signifikant skillnad (p≤0,05) mellan helblod och plasma som används i den nuvarande metoden för kapillära prover och om det finns en skillnad i stabiliteten av dessa prov. Dubbla prover togs från 30 warfarinbehandlade patienter och 5 icke warfarinbehandlade individer. Ett av proven centrifugerades och analyserades på plasma, det andra analyserades på helblod. Resultaten visade att det fanns en signifikant skillnad (p≤0,05) mellan metoderna. Bland-Altman diagrammet visade att 95 % av helblodsproverna inte var högre än 0,25 INR och lägre än 0,14 INR. Detta har en låg klinisk inverkan. 4 Proverna förvarades i rumstemperatur i upp till 24 timmar och analyserades sedan om. Ingen förändring över 10 % kunde observeras i hållbarheten. Studien visade att trots att det finns en signifikant skillnad är det möjligt att ersätta den nuvarande metoden med plasma och använda helblod istället. / Warfarin is a drug used to prevent high-risk patients such as those with atrial fibrillation from thromboembolisms. This effect is achieved by suppressing vitamin-K dependent factors VII, X and prothrombin and therefore decreasing the bloods ability to clot. Finding the right dosage of the drug for warfarin treated patients has proven difficult, as it demands regular blood draws to monitor their prothrombin complex level, which is affected by dietary and living habits. The most common way to measure prothrombin complex levels is by using venous plasma but it is also possible to use capillary plasma. Whole blood can be used for mechanical methods, which don’t use optical detection. The benefit is that whole blood doesn’t require centrifugation. The aim of this study was to investigate if there was a significant difference (p≤0,05) between using whole blood and plasma which is the existing method for capillary sample and also if there is any differences between the stability of these samples. Double samples from 30 warfarin treated patients and 5 non-treated persons were taken. One of the samples were centrifuged and analyzed on plasma and the other analyzed on whole blood. The results showed that there was a significant difference (p≤0,05) between the methods. Bland-Altman plot comparison showed that 95 % of the whole blood samples would not be higher than 0,25 INR and lower than 0,14 INR. This has low clinical impact. The samples were stored at room temperature for up to 24 hours and reanalyzed. No changes over 10 % in INR values were observed. This study showed that even though there is a significant difference, it is possible to replace the existing method which using plasma with the whole blood instead.