A anticoagulação inadequada pode ocasionar eventos tromboembólicos e hemorrágicos, representando um desafio para a medicina. A varfarina, anticoagulante oral de amplo uso, está associada a reações adversas graves, frequentes nos pacientes em tratamento com múltiplos fármacos. Objetivo: Este estudo pretende avaliar as potenciais interações medicamentosas com a varfarina, descrever e quantificar as intervenções farmacêuticas para minimizá-las, verificar o grau de aceitação da equipe médica em relação às intervenções e a repercussão no resultado do RNI. Método: Estudo de coorte, realizado entre os meses de agosto de 2009 a janeiro de 2010, envolvendo pacientes internados que iniciaram o tratamento com varfarina em duas unidades de clínica médica em um hospital universitário localizado no sul do Brasil. As potenciais interações medicamentosas com a varfarina (graves e moderadas) foram identificadas no sistema Drug-Reax, Micromedex Healthcare. Outras informações foram obtidas diretamente no prontuário. As intervenções com a equipe médica ocorreram por meio de registro em prontuário ou por informação verbal. O valor do RNI (Relação Normatizada Internacional) foi constantemente monitorado e serviu como medida do resultado da intervenção. Resultados: Foram acompanhados 202 pacientes. O total de medicamentos prescritos foi de 2071, com média de 10 (DP=3,6) por paciente. Todos pacientes apresentaram pelo menos uma interação medicamentosa potencial grave ou moderada com a varfarina, sendo a média de 3,6 (DP=1,6) por paciente. Pacientes com mais de 4 interações medicamentosas potenciais apresentaram maior risco para eventos hemorrágicos (RNI > 5 - RR = 2,57; IC95% 1,37–4,80). Foram identificadas 737 potenciais interações; 675 (91,5%) com possibilidade de potencializar o efeito anticoagulante e 29 (3,9%) de reduzir este efeito. Os medicamentos mais envolvidos em interações de potencialização foram enoxaparina (32,2%), sinvastatina (27,6%), omeprazol (22,5%) e tramadol (21,5%). Das intervenções realizadas com a equipe médica, 116 (57,4%) se deram através de registros em prontuário e 86 (42,6%) de forma verbal. Para 32 pacientes (15,8%) as intervenções não foram aceitas e estes apresentaram maior risco (RR = 2,17; IC95% 1,10 –4,27) para exame alterado (RNI > 5). Análise multivariada mostrou que idade, tempo de internação, apresentar 4 ou mais interações potenciais graves ou moderadas e não aceitar a intervenção farmacêutica contribuem significativamente para o paciente apresentar resultado de RNI > 5, o que implica em risco para eventos hemorrágicos. Conclusão: Interações medicamentosas graves e moderadas envolvendo a varfarina são muito comuns nos pacientes internados e estão associadas à maior risco do paciente apresentar RNI fora da faixa terapêutica desejada. A participação do farmacêutico no manejo das interações através de informações e orientações aos prescritores mostrou ter boa aceitação em nosso meio e parece contribuir para a segurança do paciente. / Introduction: Inadequate anticoagulation may cause bleeding and thromboembolic events, representing a challenge for medicine. Warfarin, an oral anticoagulant in wide use, has severe adverse reactions, common in patients taking multiple drugs. Objectives: This study aims to evaluate potential drug interactions with warfarin; to describe and quantify pharmaceutical interventions in order to minimize them; to assess the degree of acceptability by the medical team in relation to interventions as well as the impact on the outcome of the INR. Method: A Cohort study, done between August 2009 and January 2010 involving hospitalized patients who started warfarin therapy in two internal medicine units in a university hospital located in southern Brazil. Potential pDDIs with warfarin with warfarin (major and moderate) were identified in the online system Drug-Reax, Micromedex Healthcare. Additional information was obtained directly from medical records. Interventions with medical team were through medical record notes or verbal information. The value of the INR (international normalized ratio) was continuously monitored and served as a measure of the outcome of the intervention. Results: Two hundred and two inpatients were followed. The total number of prescribed drugs was 2071, with mean of 10 (SD = 3.6) per patient. All inpatients had at least one potential moderate or severe pDDIs with warfarin, the mean was 3.6 (SD = 1.6) per patient. Patients with more than four potential drug interactions showed a higher risk for hemorrhagic problems (INR> 5 - RR = 3.00, 95% CI 1.59-5.70). For 737 pDDIs identified, 675 (91.5%) may result in increased anticoagulation activity and 29 (3.9%) may reduce this effect. The drugs most commonly involved in these pDDIs were enoxaparin (32.2%), simvastatin (27.6%), omeprazole (22.5%) and tramadol (21.5%). The medical team’s intervention were 116 (57.4%) through medical records and 86 (42.6%) were orally. For 32 patients (15.8%), interventions were not accepted and they had higher risk (RR = 2.17; 95% CI 1.10 – 4.27) for amended exam (INR > 5). Multivariate analysis showed that age, length of hospital stay, having four or more major or moderate potential interactions and unwillingness to accept pharmaceutical intervention contribute significantly to the patient current values of INR> 5, which implies a risk of bleeding. Conclusion: Major and moderate drug interactions involving warfarin are very common in hospitalized patients and are associated with patient’s high risk of having an INR outside the target range. The collaboration of pharmacists in the management of interactions with information and guidance to physicians showed a good acceptance and seems to contribute to patient safety.

Submitted by Biblioteca da Faculdade de Farmácia (bff@ndc.uff.br) on 2017-03-20T17:23:26Z No. of bitstreams: 1 Souza, Allan Carneiro de [Dissertação, 2015].pdf: 2987434 bytes, checksum: cd3bb476893926a0cd7cc71a5e7e25e7 (MD5) / Made available in DSpace on 2017-03-20T17:23:26Z (GMT). No. of bitstreams: 1 Souza, Allan Carneiro de [Dissertação, 2015].pdf: 2987434 bytes, checksum: cd3bb476893926a0cd7cc71a5e7e25e7 (MD5) / O uso seguro de medicamentos faz parte do Programa Nacional de Segurança do Paciente. A moderna assistência farmacêutica no ambiente hospitalar lidera os processos de farmacovigilância e de boas práticas, particularmente em relação aos medicamentos de alto risco. A varfarina é um medicamento de baixo custo utilizado na prevenção de eventos tromboembólicos, porém apresenta baixo índice terapêutico podendo ocasionar sérias complicações hemorrágicas, inclusive acarretar hospitalização, portanto um exemplo de medicamento de alto risco. É importante se conhecer a efetividade da vitamina K como rastreador de EA (eventos adversos) causados por varfarina para entendermos a magnitude deste problema no ambiente dos pacientes atendidos pelo SUS. O objetivo deste estudo foi comparar a utilidade do uso da vitamina K como rastreador de eventos adversos hemorrágicos (EAH) em dois centros hospitalares (Hospital Geral x Hospital Especializado em Cardiologia) que atendem pacientes do SUS. O estudo foi realizado em dois centros: um hospital público de referência em cardiologia localizado na cidade do Rio de Janeiro (Hospital E) e um hospital público geral e de emergência do município de Macaé (Hospital G). O método dos rastreadores ou trigger tools foi aplicado para análise retrospectiva da utilização da vitamina K (fitomenadiona) como rastreador de eventos adversos hemorrágicos causados por varfarina. As principais variáveis determinadas no estudo foram: rendimento da vitamina K em detectar eventos, classificação dos eventos adversos a medicamentos (EAM) quanto à causalidade através do algoritmo de Naranjo e quanto ao grau de dano. Outros indicadores calculados foram taxa de eventos adversos como causa de admissão hospitalar e tempo médio para análise dos prontuários que foi determinado apenas no Hospital G. O uso da vitamina K foi avaliado em 46 prontuários no Hospital E e 54 prontuários no Hospital G. No Hospital G dois pacientes sofreram sangramentos pelo uso de varfarina, resultando assim em um rendimento de 3,7% (2/54) na capacidade da vitamina K em detectar eventos adversos hemorrágicos, bem inferior ao rendimento deste rastreador encontrado no Hospital E que foi de 30,4% (14/46). Na análise da causalidade dos danos hemorrágicos, todos os eventos adversos, identificados em ambos os hospitais foram classificados como prováveis após a aplicação do algoritmo de Naranjo. Grande parte dos EA identificados nos dois centros foram classificados como H, onde houve necessidade de medidas de suporte à vida como infusão de plasma e ou hemácias. No Hospital E a idade média dos pacientes que sofreram EA hemorrágicos foi 57,4 anos (dp=15,2). Em relação ao estudo realizado no Hospital G, os dois pacientes que apresentaram EAH tinham idade superior a 70 anos. No Hospital E, em 50% (7/14) dos pacientes, a hemorragia foi a causa da internação. Enquanto no Hospital G os dois pacientes que sofreram EAH por varfarina foram internados devido a ocorrência do sangramento. No estudo realizado no Hospital E treze pacientes que sofreram EAH tinham RNI ≥ 6. O odds ratio (od) de EAH com RNI ≥ 6 foi de 24,9. No estudo do Hospital G não foi possível calcular o odds ratio, pois raramente havia registro dos valores de RNI. Conclusão. No Hospital G o uso da vitamina K como rastreador esteve pouco associado a eventos adversos hemorrágicos por varfarina. Enquanto no hospital cardiológico foi observada elevada associação / The safe use of medicaments is part of the Brazilian Patient Safety Programme. Modern pharmaceutical care in the hospital domain is the chief item in the processes of pharmacovigilance and good practices, particularly as regards high-risk medications. Warfarin is a low-cost medication used in the prevention of thromboembolic events, but has a low therapeutic index, and may cause severe haemorrhagic complications, including the need for hospitalisation, being therefore a high-risk medication. Knowing how effective vitamin K, as a trigger of haemorrhage Adverse Events (AEs) caused by warfarin, is important to understand the magnitude of the problem in the realm of the patients of the SUS (Brazilian Health System). The objective of this study was to compare the usefulness of the use of Vitamin K as a trigger of adverse haemorrhage events in two hospital centres (General Hospital vs a Cardiology Specialist Hospital) that care for SUS patients. The study was undertaken in two centres: a public Cardiology reference hospital in the city of Rio de Janeiro (Hospital E) and a public general and emergency hospital in the city of Macaé (Hospital G). The trigger tools method was applied in a retrospective analysis of the use of Vitamin K (phytomenadione) as a trigger of adverse haemorrhage events caused by warfarin. The main variables established in the study were: performance of the Vitamin K in detecting events (EAH), classification of the adverse drug events (ADEs) as regards the causality via the Naranjo algorithm, and as regards the damage level. Other pointers calculated were the rate of adverse events as cause for hospital admittance and mean time for the analysis of the medical records, done only at Hospital G. The use of Vitamin K was assessed in 46 medical records in Hospital E and in 54 medical records in Hospital G. The latter had two patients who underwent bleeding through the use of warfarin, thus yielding a 3.7% (2/54) performance rate for Vitamin K in detecting adverse haemorrhage events, well below the efficiency for this trigger as found in Hospital E, at 30.4% (14/46). In the analysis of causality of the haemorrhagic data, all the adverse events identified in both hospitals were rated as probable after the application of the Naranjo algorithm. A major part of the AEs identified in the two centres was rated as H, where there was a need to deploy life support measures, such as plasma and/or red blood cell infusions. The average age, in Hospital E, of the patients that had adverse haemorrhage events was 57.4 years (dp=15.2). The study done in Hospital G had two patients aged over 70 who experienced SHE. At Hospital E, 50% (7/14) of the patients had an haemorrhage as the cause for hospital admission. In Hospital G the two patients who experienced a coumarin-related episode were admitted due to bleeding after the use of warfarin. In the study done at Hospital E thirteen patients who went through haemorrhage AEs had a RNI ≥ 6. The odds ratio for bleeding with a RNI ≥ 6 was of 24.9. On the other hand, in the study done at Hospital G it was not possible to calculate the odd ratio as there rarely was a record for the values of the RNI. The use of Vitamin K, as a trigger, at the General Hospital was little associated to adverse haemorrhage events due to warfarin. A substantial association was observed, however, at the Cardiology Hospital

The anti-coagulant warfarin is consumed by around 200 000 people in Sweden every year. There are many dose affecting factors, and if the dose is wrong the consequences can be severe. Hence patients are required to regularly have their coagulation ability tested so that the dosage can be adjusted if needed. In this study the dosage regulation processes of warfarin in Swedish home care are examined through a case study, where-after an information infrastructure design is created that could support the identified needs. The proposed design is formed through combining three separate IT-capabilities: a general purpose health care platform, a warfarin specialist software and a medication reminder application. The design was guided by the application of the information infrastructure design rules with the aim of uncovering problems and possibilities associated with this design approach. By applying the information infrastructure design rules a technical architecture could successfully be created. Additionally, information exchange specifications and important decision making points could be identified or solved successfully. However the design rules were found to assume an unlikely level of openness and to lack a focus on organizational and legal factors which make them difficult to apply in practice.

Class of 2015 Abstract / Objectives: To determine if using three-factor prothrombin complex concentrate (PCC) immediately prior to heart transplantation reduces blood product transfusions in patients bridged to heart transplantation by mechanical circulatory support (MCS) devices who are treated with warfarin. Methods: This study retrospectively reviewed patients that either received PCC or received usual care (i.e. fresh frozen plasma – FFP) prior to heart transplantation. Outcomes that were evaluated included packed red blood cell (RBC), FFP, platelet and cryoprecipitate transfusions intra and five days post-operatively, Cell Saver autologous blood volume administered intra-operatively, chest tube output for the five days post-operatively, and thromboembolic events post-operatively. Results: There were 24 patients included in the study, 12 from each group. The PCC group showed significantly less intra-operative RBC transfusion (2.60 ± 1.49 units vs. 5.09 ± 2.42 units, p=0.018), Cell Saver autologous blood usage (2.60 ± 1.49 units vs. 4.02 ± 1.55 units, p=0.032), and FFP transfusion (2.14 ± 2.30 units vs. 10.94 ± 5.96 units, p=0.0005) than the usual care group. There was no difference in amount of vitamin K given, change in INR, platelets administered, cryoprecipitate administered, chest tube output, or thromboembolic events between the groups. The average dose of PCC was 31 units/kg IV; repeat doses were given to 2 patients. Conclusions: We propose that the use of PCC prior to heart transplant surgery for patients on MCS devices anticoagulated with warfarin may result in the reduction for the need of RBC’s, autologous blood use and FFP during surgery.

Patients with inflammatory bowel disease (IBD) are known to have an increased propensity for thromboembolic events. Like any patient with a high risk of event recurrence, most of these patients can be managed successfully with long-term warfarin therapy. We present the case of a 66-year-old woman with Crohn's disease who, despite careful attention to the management of her international normalized ratio, developed a new deep vein thrombosis and required inferior vena cava filter placement in addition to ongoing warfarin therapy to prevent recurrent pulmonary emboli. This report serves as a reminder to physicians to have a low threshold for diagnosing thromboembolic events in patients with IBD, even if they are presumed to be adequately anticoagulated. Known and theoretical contributing factors to this increased clotting tendency are also reviewed.

Anticoagulation risks in older adult, long-term care patients are known to be high, especially in those with frequent transitions between care environments. Introduction of collaborative practice agreements (CPA) in specific settings is encouraged in the United States and has provided an additional option for the care of medically challenging patients. The aim of this study was to investigate the time in therapeutic range (TTR) in a Medicare Part A sponsored long-term care environment managed by pharmacists through a collaborative practice agreement in South-Central Appalachia. A retrospective review of all warfarin patient admissions from a large long-term care pharmacy’s anticoagulant clinic was conducted for residents over an 18-month period. For all patients (n = 104), the overall TTR was 46.7% (INR 43% in range). Average management duration was 19.5 days per patient. Further studies are required to optimize CPA and transition strategies for complex, advanced age warfarin patients.

People at risk for blood clots are often treated with anticoagulants, warfarin is such an anticoagulant. The dose's effect is measured by comparing the time for blood to clot to a control time called an INR value. Previous anticoagulant studies have addressed agreement between fingerstick (POC) devices and the standard laboratory, however these studies rely on mathematical formulas as criteria for clinical evaluations, i.e. clinical evaluation vs. precision and bias. Fourteen such criteria were found in the literature. There exists little consistency among these criteria for assessing clinical agreement, furthermore whether these methods of assessing agreement are reasonable estimates of clinical decision-making is unknown and has yet to be validated. One previous study compared actual clinical agreement by having two physicians indicate a dosing decision based on patient history and INR values. This analysis attempts to justify previously used mathematical criteria for clinical agreement. Generalized additive models with smoothing spline estimates were calculated for each of the 14 criteria and compared to the smoothing spline estimate for the method using actual physician decisions (considered the "gold standard"). The area between the criteria method spline and the gold standard method spline served as the comparison, using bootstrapping for statistical inference. Although some of the criteria methods performed better than others, none of them matched the gold standard. This stresses the need for clinical assessment of devices.

<p><strong>BACKGROUND</strong></p> <p>Amiodarone is believed to inhibit the hepatic metabolism of warfarin, potentiating its hypoprothrombinemic effect and increasing the risk of hemorrhage. The consequences of this drug interaction on important clinical outcomes are unknown.</p> <p><strong>METHODOLOGY</strong></p> <p>Using linked health administrative databases, we conducted a population-based retrospective cohort study among Ontario residents aged 66 years or older who had been treated with warfarin therapy for at least 6 months. Within this group, we identified subjects who initiated amiodarone while on warfarin. Each of these subjects was matched to a subject not treated with amiodarone on age, sex, year of cohort entry, and a high dimensional propensity score. The primary outcome was a hospitalization due to a hemorrhagic event within 30 days of follow-up. In a secondary analysis, we examined in-hospital mortality following hospitalization for major hemorrhage.</p> <p><strong>RESULTS</strong></p> <p>We identified 60,497 eligible patients between July 1, 1994 and March 31, 2009. Of these, 11,665 (19.3%) received a new prescription for amiodarone while receiving ongoing warfarin therapy and 7,124 (61.1%) of these were matched to a subject who was not exposed to amiodarone while receiving warfarin therapy. The median age at cohort entry of the matched cohort was 76 years, 51.6% in the cohort were male, 14.5% lived in a rural location, 2.8% had a bleed in the past year, and 21.6% had a diagnosis of congestive heart failure in the past year. Fifty-six amiodarone recipients experienced a hemorrhagic event (0.8%) as compared to 23 individuals (0.3%) in the non-exposed group at 30 day follow-up (adjusted hazard ratio (HR) = 2.45; 95% CI, 1.49 to 4.02). Seven patients in the amiodarone group died after hospitalization for a hemorrhage versus four in the non-exposed group (adjusted HR = 1.74; 95% CI, 0.25 to 12.24).</p> <p><strong>CONCLUSION</strong></p> <p>Initiation of amiodarone in patients on chronic warfarin therapy was associated with a two-fold increase in the risk of hospitalization due to a hemorrhagic event. Physicians should closely monitor the response to warfarin following initiation of amiodarone.</p> / Master of Science (MSc)

Yes / Introduction: Oral anticoagulant therapy choices for patients with atrial fibrillation (AF) expanded in the last decade with the introduction of direct oral anticoagulants (DOAC). However, the implementation of DOACs was slow and varied across different health economies in England. There is limited evidence on the patient role in the uptake of new medicines, including DOACs, apart from considering their demographic and clinical characteristics. Hence, this study aimed to address the gap by exploring the view of patients with AF on factors affecting DOAC use. Methods: A qualitative study using semi-structured interviews was conducted in three health economies in the North of England. Adult patients (>18 years) diagnosed with non-valvular AF, prescribed an oral anticoagulant (vitamin K antagonist or DOAC), and able to give written consent were recruited. Data were collected between August 2018 and April 2019. Audio recorded interviews were transcribed verbatim and analyzed using the framework method. Results: Four themes with eleven subthemes discussed identified factors affecting the use of DOACs. They were linked to limited healthcare financial and workforce resources, patient involvement in decision-making, patient knowledge about DOACs, safety concerns about oral anticoagulants, and oral anticoagulant therapy impact on patients' daily lives. Lack of a) opportunities to voice patient preferences and b) information on available therapy options resulted in some patients experiencing difficulties with the prescribed therapy. This was reported to cause negative impact on their daily lives, adherence, and overall satisfaction with the therapy. Conclusion: Greater patient involvement in decision-making could prevent and resolve difficulties encountered by some patients and potentially improve outcomes plus increase the uptake of DOACs. / Pharmacy Research UK (PRUK-2018-GA-1-KM) and Leeds Teaching Hospitals NHS Trust

Yes / Direct oral anticoagulants (DOACs) uptake for stroke prevention in atrial fibrillation has been slow.[1] This study aimed to profile the prescribing of DOACs over three years to identify factors associated with DOAC prescribing in a Clinical Commissioning Group (CCG) without restrictions to DOACs use. The objectives were to identify: - Characteristics of patients prescribed oral anticoagulant (OAC) in a sample of general practices; - Who initiated the prescribing of OAC; - Recorded reasons for prescribing a DOAC rather than warfarin;