Thèse d'exercice : Pharmacie : Université de Nantes : 2007. / Bibliogr.

Thèse d'exercice : Médecine. Médecine générale : Nantes : 2007. / Bibliogr.

The purpose of this study was to characterize the association between anti-prothrombin antibodies and the lupus anticoagulant (LA) in order to elucidate the antigenic site of the LA. Plasma from 8 patients with the LA had evidence of anti-prothrombin antibodies on prothrombin crossed immunoelectrophoresis as characterized by material moving slower in the first dimension of electrophoresis than normal prothrombin, i.e., a trailing shoulder. Four of 5 LA patients with a prolonged prothrombin time demonstrated the most pronounced evidence of anti-prothrombin antibodies. All patients were shown to have an essentially normal level of prothrombin antigen. Using an enzyme-linked immunosorbent assay (ELISA), six of 8 LA patients tested positive for anticardiolipin antibodies (aCL) of the IgG isotype while 7 of 8 LA patients tested positive for antiphosphatidylserine antibodies (aPS) of the IgG isotype.An anti-human Factor II (prothrombin) ELISA was developed to confirm the presence of anti-Factor II (aFII) activity in LA patients. Seven of 8 LA patients were positive for aFII activity. A strong parallel existed between the presence of aPS activity, anti-human Factor II activity, and the LA, i.e., 7 of 8 LA plasmas were aPS (+)/aFII (+). An antibovine Factor II ELISA was developed to determine if the aFII activity associated with LA patients is speciesspecific. Three of 5 LA patients positive for anti-human Factor II activity were also shown to be positive for antibovine Factor II activity. Antibodies with specificity for human prothrombin were purified from LA plasmas using a prothrombin affinity column. Three of 8 LA patient eluates were shown to be positive for aPS (IgG) while none were positive for aCL (IgG or IgM) or human aFII activity. Affinity-purified eluates were assayed for LA activity using the dilute Russell viper venom time (dRVVT). None of the LA patient eluates were shown to prolong the dRVVT when present with normal plasma in concentrations up to 100 micrograms/mL. / Department of Chemistry

Thesis (MAppSc (Medical Laboratory Science)) --University of South Australia, 1992

Thesis (Ph. D.)--Duke University, 2008.

Trombotic diseases are a global health problem of multifactorial and multigenic etiology. They are characterized by the acute formation of trombus in veins and arteries. The oral anticoagulants are applied in order to create a partial deficiency on the active form of vitamin K, a co-factor in the changing of the factors of vitamin K-dependents coagulation, so that the risk of an abnormal coagulation can be reduced. The anti-vitamin K drugs or oral anticoagulants avoid the carboxylation of the II, VII, IX and X coagulation factors leading to the synthesis of the inactive factors. Several substances can change the action of oral anticoagulants, decreasing their action and increasing the thrombotic risk or increasing their activity and enlarging the blooding risk. The laboratory control of the oral anticoagulation is accomplished through the Time of Protrombine (TP) and of the Partial Thromboplastin Time (TTP) which are responsible for the success and safety of this therapeutic procedure. The present work has analyzed the parameters regarding the laboratory accompaniment of patients in use of oral anticoagulants as well as their interference on the medicine effect aiming to reach a better security for this kind of treatment. We can notice that most of the patients have made use of a quite rich diet in vitamin K producing variations in the values of their Normalized International Reasons (INRs) and consequently a larger difficulty in finding the right dose of the medicine for each patient. It also may be concluded that the anticoagulants response is influenced by some factors and those ones must be considered as, for example, the use of other medicines which affects the release or the absorption of the drug, laboratory technical troubles and the individual variability of each patient in relation to the drug. / As doenças trombóticas constituem um problema de saúde mundial de etiologia multifatorial e multigênica. São caracterizadas por formação aguda de trombos em veias e artérias. Os anticoagulantes orais são usados para criar uma deficiência parcial da forma ativa da vitamina K, um cofator na modificação dos fatores da coagulação vitamina K-dependentes e, assim, reduzir o risco de uma coagulação anormal. Os fármacos antivitamina K ou anticoagulantes orais impedem a carboxilação dos fatores II, VII, IX e X da coagulação, levando à síntese de fatores inativos. Uma série de substâncias pode alterar a ação dos anticoagulantes orais, reduzindo sua ação e aumentando o risco trombótico ou aumentando sua atividade e elevando o risco de sangramento. O controle laboratorial da anticoagulação oral é feito através do Tempo de Protrombina (TP) e do Tempo de Tromboplastina Parcial (TTP), os quais são responsáveis pelo sucesso e segurança deste procedimento terapêutico. Neste trabalho, foram analisados os parâmetros relativos ao acompanhamento ambulatorial de pacientes em uso de anticoagulantes orais e a interferência destes na atividade do fármaco em questão, buscando, dessa forma, uma melhor segurança para este tipo de tratamento. Observo-se que grande parte dos pacientes fazia uso de uma dieta bastante rica em vitamina K, o que acarretava variações nos valores de suas Razões Normalizadas Internacionais (INRs) e, com isso, uma dificuldade maior em encontrar a dose adequada do medicamento para cada paciente. Também se pode concluir que a resposta dos anticoagulantes é influenciada por alguns fatores e estes devem ser considerados como, por exemplo, o uso de outros medicamentos que afetem a liberação ou absorção do fármaco, problemas técnicos de laboratório e a variabilidade individual de cada paciente frente ao medicamento.

Orientador: Marcos Augusto de Moraes Silva / Resumo: Estudo realizado, com base nos dados do ambulatório, para controle de anticoagulação nos pacientes portadores de próteses valvares cardíacas mecânicas do Serviço de Cirurgia Cardiovascular do Hospital das Clínicas da Faculdade de Medicina de Botucatu, no intervalo de dez anos, com os objetivos: avaliação da resposta à terapêutica profilática anticoagulante; quantificação das complicações tromboembólicas e hemorrágicas, com estratificação de sua gravidade; comparação entre tipos de anticoagulantes orais, doses e efeitos; influência da posição da prótese; presença de fibrilação atrial e tamanho do átrio esquerdo; e análise da estratégia de anticoagulação adotada. Foram incluídos, no estudo, 259 pacientes portadores de próteses mitrais (mitrais), aórticas (aórticos) e mitral e aórticas (mitro-aórticos). Foram analisadas 9714 consultas com valores do tempo de protrombina (em RNI) e dados dos registros hospitalares sobre complicações tromboembólicas e hemorrágicas com graus de gravidade. Os pacientes foram divididos em quatro grupos de acordo com o porcentual de consultas em que a RNI se encontrava dentro do intervalo desejado. Foram estudados dois anticoagulantes (Fenprocumona e Warfarina) e suas dosagens. Foi, também, avaliada a ocorrência de complicações tromboembólicas e hemorrágicas. Os resultados estão apresentados em: número de pacientes com complicações, estudo atuarial e freqüência linearizada de ocorrência de eventos. Os dados obtidos permitiram concluir que: a anticoagulação oral foi mais satisfatória nos aórticos do que nos mitrais e mitro-aórticos; os mitrais apresentaram ocorrência de eventos tromboembólicos semelhante a dos aórticos, porém com maior freqüência de hemorragias; os grupos que tiveram anticoagulação mais estável apresentaram menos complicações; poucas diferenças quanto à ocorrência de... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The study was held using outpatient data collected during 10 years for anticoagulation control of patients with mechanical prosthetic heart valves from the Cardiovascular Surgery Service at the Medical University Hospital in Botucatu city. The objectives were as follows: evaluation of prophylactic anticoagulation therapy, number of thromboembolic and hemorrhagic complications and their severity stratification, assessment of different oral anticoagulants, their effects and dosing, influence of prosthesis position, presence of atrial fibrillation and size of the left atrium, assessment of the anticoagulation strategy. Two hundred and fifty nine patients with mitral (M), aortic (A), mitral and aortic (M-A) prostheses were included in the study. Prothrombin time expressed in terms of international normalised ratio (INR) from 9714 consultations, medical data on thromboembolic and hemorrhagic complications as well as their severity were evaluated. Patients were allocated to four groups according to percentage of consultations which INR was within the target range. Two anticoagulants (Fenprocoumon and Warfarin), their dosing system, thromboembolic and hemorrhagic complications were also evaluated. Results were expressed as: number of patients with complications, actuarial study and linearized rate of events. Conclusions: oral anticoagulation was better in A than in M or M-A patients; M patients presented as many thromboembolic events as A patients although with higher hemorrhagic rate; groups presenting more steady anticoagulation showed fewer complications; there were few differences concerning complications among users of Fenprocoumon and Warfarin; most patients needed lower anticoagulant doses; patients with atrial fibrillation and/or enlarged left atrium presented as many thromboembolic complications as the other studied patients, although with higher... (Complete abstract click electronic access below) / Doutor

Class of 2016 Abstract / Objectives: To identify common and serious drug-drug interactions involving novel anticoagulant drugs in cancer patients. Subjects: 60 patients who were treated at the Banner University of Arizona Cancer Center between November 1, 2013 and April 1, 2015 with rivaroxaban, dabigatran, or apixaban. Methods: A retrospective chart review was performed for patients who received a NOAC (novel oral anticoagulant) to determine if a medication regimen contained a drug-drug interaction involving the NOAC. Results: When analyzing the DDIs involving rivaroxaban, dabigatran, and apixaban, Micromedex® detected a total of 123 interactions, compared to Lexicomp®, which detected 111 interactions. When using Lexicomp®, there were 59 (32%) instances of no detected interactions, 19 (10%) moderate interactions, 27 (15%) major interactions, and 65 (36%) contraindicated DDIs with rivaroxaban. When using Micromedex®, there were 47 (26%) instances where no interaction was detected, 4 (2%) moderate interactions, and 119 (65%) major interactions, and no interactions were classified as contraindicated with rivaroxaban. Lexicomp® detected 3 (50%) interactions as major, and found no DDIs in 3 (50%) instances for dabigatran, and detected 1 (7%) moderate, 2 (14%) major and 6 (43%) contraindicated interactions for apixaban. Micromedex® detected 3 (50%) interactions as major, and found no DDIs in 3 (50%) instances for dabigatran, and detected 12 (86%) of interactions as major and found no DDIs in 2 (14%) instances for apixaban. Conclusions: There was significant variation in DDI detection between current literature4,5 and the drug information databases, Lexicomp® and Micromedex®, however most interactions detected were major or contraindicated.

Class of 2011 Abstract / OBJECTIVES: To assess the outcomes of care for patients enrolled in a pharmacist-run anticoagulation clinic. METHODS: A retrospective chart review was conducted of patients who received warfarin anticoagulation therapy management at the pharmacist-managed clinic at a community health center. To be eligible for the study patients had to be between the ages of 18-80 and have at least 6 recorded INRs during the first 6 months of treatment in the clinic. The patient data were reviewed for a time period of 24 weeks from the initial visit. The primary dependent variable was whether or not a patient’s INR is within range. Secondary outcomes included frequency of adverse events (blood in urine or stool). A data extraction form was used to collect patient demographics and initial INR values from the patient charts. An odds ratio was used to compare the proportion of INRs in range upon entry into the clinic and after 6 months of care in the clinic. In addition, outcomes were evaluated for differences by gender and age. RESULTS: Sixty-six patients were included in the study; 50% (33) were men and the average age was 55.9 years old (SD = 12.9 years). At baseline, 24 patients had INRs within the therapeutic range. Patients were 5 times more likely to have INRs in range (N = 49; OR = 5.04; p < 0.001) after 6 months of treatment in the pharmacist-managed clinic than at baseline. About 59% of men and 54% of women had INRs in range during 6 months of therapy in the clinic (p=0.326). Patients under 55 were in range about 55% of the time over 6 months, while patients over 55 were in range about 59% of the time (p=0.366). CONCLUSION: Patients enrolled in the pharmacist-run anticoagulation clinic were more likely to have therapeutic INRs after 6 months of care in the clinic compared to baseline.

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