Academic literature on the topic 'Anticoagulation monitoring'

La problématique de cette thèse est la caractérisation des complications liées à l’hémostase chez le patient assisté par ECMO-VA périphérique afin d’en améliorer la prévention et de rationaliser les approches antithrombotiques en usage. Dans une première étude, nous avons décrit qualitativement et quantitativement la composition des thrombi formés sur les circuits d’ECMO-VA. Nous avons observé que ces thrombi sont majoritairement composés de VWF, de fibrine et dans une moindre proportion de plaquettes et d’érythrocytes. Notre approche quantitative a également permis de mettre en évidence la présence de NETs en l’absence de toute pathologie septique active, confirmant la possibilité d’une NETose aseptique sous ECMO-VA. Par une analyse en cluster hiérarchique, nous avons identifié 2 types de thrombi pouvant relever chacun d’un mécanisme de formation différent. Dans cette étude, la localisation des thrombi sur le circuit d’ECMO-VA n’impactait pas leurs compositions, ce qui souligne l’hétérogénéité des thrombi formés sous ECMO-VA et la multiplicité des mécanismes à l’origine de la thrombinoformation dans ce contexte. Dans un second travail, nous avons comparé la performance des revêtements de surfaces des circuits d’ECMO-VA à réduire la thrombinoforation et ses conséquences cliniques. Deux des revêtements les plus utilisés en routine étaient comparés : celle à base de phosphorylcholine et à base d’héparine. Nous avons observé un taux de complications thrombotiques plus conséquent dans le groupe phosphorylcholine sans surrisque hémorragique ou de mortalité dans les deux groupes. Par ailleurs, comparativement aux thrombi issus des jonctions de circuits traités par revêtement de phosphorylcholine, ceux provenant de circuits traités par polysaccharide-albumine étaient plus pauvres en VWF. Notre travail suggère que l’intensité de l’anticoagulation devrait être modulée en fonction du type de revêtement de surface du circuit d’ECMO. Notre troisième étude avait pour but d’identifier les saignements les plus graves justifiants d’une prise en charge clinique agressive et d’un investissement plus conséquent en recherche. À cette fin, nous avons comparé l’association entre 3 classifications de saignement avec la mortalité à 28 jours. La définition ELSO déjà en usage et les classes de la classification BARC ≥ type 2 étaient associées à la mortalité et retenues donc comme définitions de l’hémorragie majeure. Les facteurs biologiques prédictifs de l’hémorragie grave d’après la définition de l’ELSO étaient la baisse du fibrinogène, du compte plaquettaire et de l’hémoglobine à la canulation. L’indice de masse corporelle et l’étiologie postcardiotomie étaient également prédictifs de la survenue de cette complication. Dans un travail additionnel portant sur la thématique de la thèse, nous avons étudié deux des tests les plus utilisés pour la surveillance de l’héparinothérapie systémique sous ECMO, le TCA et l’activité Anti-Xa afin d’identifier le plus pertinent. Pour ce faire, dans un premier objectif nous avons étudié la relation entre ces deux tests puis avons analysé dans un second objectif l’impact de facteurs biologiques d’influences sur cette relation. Ensuite, nous avons déterminé leurs associations avec les complications thrombotiques et hémorragiques. Bien qu’étant linéairement associé, le taux de discordance entre leurs mesures était de 39 % pour une fenêtre référence d’Anti-Xa de 0,3 — 0,7 UI/mL. Ni le TCA et ni l’Anti-Xa n’étaient associées aux complications thrombotiques ou hémorragiques [...]<br>The purpose of this dissertation is to characterize hemostasis-related complications in patients supported by peripheral VA-ECMO to improve their prevention and to optimize the antithrombotic therapeutic approaches in use. In a first study, we qualitatively and quantitatively described the composition of thrombi collected from the VA-ECMO circuits. We observed that these thrombi are mainly made of VWF, fibrin and in a lesser proportion of platelets and RBCs. Our quantitative approach also allowed us to demonstrate the presence of NETs while there was no active septic, confirming the possibility of aseptic NETosis under VA-ECMO. By hierarchical cluster analysis, we identified 2 types of thrombi, each of which may be related to a different mechanism of formation. In this study, the location of thrombi on the VA-ECMO circuit did not impact their compositions, highlighting the heterogeneity of thrombi formed within VA-ECMO and the multifactorial mechanisms that support thrombosis in this setting. In a second study, we compared the performance of surface coatings on VA-ECMO circuits to reduce thrombinoformation and its clinical consequences. Two of the most used coatings in daily practice were compared: the phosphorylcholin-based coating and the polysaccharide-albumin-based coating. We observed a higher rate of thrombotic complications in the phosphorylcholin group without any excess bleeding events or mortality in either group. In addition, compared with thrombi from phosphorylcholin-coated circuit junctions, those from polysaccharide-albumin-coated circuits were poorer in VWF. Our work suggests that the level of anticoagulation should be modulated according to the type of coating of the ECMO circuit.The aim of our third study was to identify the most relevant bleeding events that may guide clinical decision-making for more aggressive clinical management and a greater investment in research. To this end, we compared the association between 3 bleeding classifications with 28-day mortality. The ELSO definition already in use and the BARC classification classes ≥ type 2 were associated with 28-day mortality and thus retained as definitions of major bleeding. Laboratory parameters that are predictors major bleeding according to the ELSO definition were decreased fibrinogen, platelet count, and hemoglobin at cannulations. Body mass index and postcardiotomy etiology were also predictive of ELSO major bleeding. In an additional work related to the topic of the thesis, we studied two of the most used laboratory tests for the monitoring of systemic heparin during VA-ECMO, the APTT and the Anti-Xa activity, to identify the most relevant. First, we studied the relationship between these two tests and then analyzed in a second objective the impact of biological influencing factors on this relationship. Next, we determined their associations with thrombotic and hemorrhagic complications. Although linearly associated, the rate of discordance between their measurements was 39 % for an Anti-Xa reference range of 0.3 - 0.7 IU/mL. Neither APTT nor Anti-Xa was associated with thrombotic or bleeding complications. Taken together, our results highlight the heterogeneity of thrombi from peripheral VA-ECMO, the involvement of numerous causal factors that underline thrombotic and hemorrhagic complications, both not predictable by routine tests. Finally, our work underscored the need for new approaches in thrombotic or hemorrhagic complications management with targets set at an individual level considering both patient and ECMO circuit characteristics

Warfarin has been the mainstay of preventing and treating thromboembolism for over 50 years and is currently taken by over 200,000 Australians. Optimal management of warfarin relies on regular monitoring of the International Normalised Ratio (INR), appropriate dose adjustment, effective communication and comprehensive patient education. Therapy may be managed by a range of healthcare providers in a variety of settings, and by patients themselves, although management in Australia has tended to focus on traditional office and pathology based models. Internationally, however, alternative models of care are playing an increasingly significant role with positive results and pharmacists have been shown to be effective in improving the quality use of warfarin through a variety of these service delivery models. The main objective of this thesis was to examine the effect of using pharmacist delivered models of care on warfarin management within Australia through a number of complementary projects. Guidelines recommend aiming for a target INR control of upwards of 70% time in range. Internationally, community-based studies consistently demonstrate suboptimal levels of INR control, although little data is available on the level of control achieved through usual models of care in Australia. A retrospective cross sectional study of INR results from 442 Australian veterans was undertaken to determine the INR control of a usual care population. The mean time in INR range was 61.8% in this population. This suggests a potential role for strategies aiming to improve INR control among Australian patients in line with best practice guidelines. Review of the literature suggested pharmacists could play a role in improving warfarin management through optimising the delivery of education, improving access to INR testing and facilitating patient self-monitoring. A series of sub-projects were designed to develop and pilot tools to support pharmacists in addressing these strategies. A website was designed to provide patients and health professionals with educational resources regarding anticoagulation. The site aimed to be a comprehensive and reliable online resource and was promoted directly to pharmacists. It received high levels of utilisation, with almost 250,000 views in 12 months, and positive feedback from health professionals and patients, and proved to be an important educational resource that was an easy and accessible tool for pharmacists to use to complement face to face counselling services and further improve patients’ knowledge about warfarin therapy. Tools and resources were developed to improve access to INR testing by facilitating the introduction of anticoagulation services, including pharmacist-delivered INR clinics, in Australia. A pilot was conducted in three rural community pharmacies, with a subsequent project involving 36 pharmacies. While the resources received positive feedback from participating pharmacists, the rate of successful service implementation was low. Despite the perceived benefits to the communities, the current model of healthcare remuneration in Australia impacted on the long term financial viability of such services. Development, implementation and evaluation of a pharmacy-centred pathway to enable patient self-monitoring (PSM) was also undertaken. Forty-eight patients successfully underwent training and participated in PSM for a median of 16.9 months. INR control data during PSM was compared to that from the six months prior to entering the study for 46 of the 48 patients. There was a significant improvement in INR control, with the mean time in range increasing from 64.0% to 72.9% (p<0.05). Clinical data analysis was complemented by a qualitative exploration of 38 patients’ experiences of self-monitoring and the impact of PSM on various aspects of their lives. It was found that patients discussed PSM positively, describing it passionately and as something of value, which reduced their anxiety and freed them to carry on with their lives. The results of these projects suggest that expansion of the professional services offered by pharmacists has the potential to improve the control of warfarin therapy in Australia. Changes in remuneration for healthcare services are likely to increase the viability of pharmacist-delivered INR services and the uptake of PSM. Despite the arrival of newer oral anticoagulant agents, the use of warfarin is likely to continue for many years. Optimising warfarin management is arguably the safest and most clinically and cost-effective option for preventing and treating thromboembolism at this point in time. Pharmacists can play an important role in improving warfarin management by embracing opportunities to deliver professional services aimed at optimising outcomes for Australians taking warfarin.

Dissertação de Mestrado em Farmacologia Aplicada apresentada à Faculdade de Farmácia<br>Racional: Os anticoagulantes orais são habitualmente utilizados na prática clinica para o tratamento e prevenção de doenças cardiovasculares, acidentes cerebrovasculares e tromboembolismo venoso. Para além dos antagonistas da vitamina K, surgiram recentemente outros anticoagulantes orais com um mecanismo de ação mais específico e aparentemente com menos limitações. Os novos anticoagulantes dispensam a monitorização analítica de rotina, mas não dispensam o acompanhamento do doente por um profissional de saúde, com o objetivo de aumentar a eficácia e segurança e maximizar a adesão á terapêutica. O farmacêutico, pelos seus conhecimentos no âmbito da farmacologia e pelo sucesso de programas de acompanhamento farmacoterapêutico, desenvolvidos em outras áreas como por exemplo a hipertensão e a diabetes, está bem posicionado para uma intervenção na gestão e acompanhamento do doente anticoagulado.Objetivo: Este trabalho pretende dar um contributo na área em 3 vertentes:1. Fazer uma revisão dos modelos existentes em outros países de acompanhamento farmacoterapêutico de doentes medicados com anticoagulantes orais.2. Criar em Portugal um método para implementar a consulta farmacêutica de acompanhamento do doente sob anticoagulação oral.3. Identificar necessidades de formação que conferem competências ao farmacêutico para fazer o acompanhamento do doente anticoagulado.Métodos: • Pesquisa na Pubmed, e em outras fontes consideradas relevantes para o tema, com o objetivo de ver o que existe publicado na área.• Os parâmetros relevantes para uma correta utilização dos anticoagulantes e acompanhamento farmacoterapêutico destes doentes são definidos com base na informação encontrada e nas características de cada fármaco.• Criação de estrutura de programa de formação para farmacêuticos.Resultados: Foi feita uma revisão dos modelos de acompanhamento de doentes anticoagulados existentes em outros países quer para os fármacos antivitamínicos K quer para os anticoagulantes orais não antagonistas da vitamina K. Foram consultadas as principais Guidelines na área e as recomendações das sociedades científicas envolvidas na utilização de anticoagulantes orais. Verificou-se que existem registos de sucesso de programas de monitorização da anticoagulação com impacto na melhoria da correta utilização dos antagonistas da vitamina K. Estes programas de acompanhamento começam a incluir os novos anticoagulantes nos seus protocolos.Com base na informação encontrada, foi criado um modelo de acompanhamento destes doentes pelo farmacêutico, com o objetivo de melhorar a eficácia e a segurança na utilização destes fármacos. Em função dos conhecimentos requeridos ao farmacêutico para que possa de forma cabal desenvolver esta atividade, é proposta uma formação estruturada na área da anticoagulação que lhe permitirá o desenvolvimento destas competências.Conclusão: Este trabalho permitiu criar um modelo de consulta farmacêutica para acompanhamento de doentes anticoagulados, para futura validação na realidade portuguesa. Espera-se assim que este modelo contribua para a melhoria do controlo dos doentes anticoagulados em Portugal, em âmbito de consulta farmacêutica.<br>Rationale: Oral anticoagulants are commonly used in clinical practice for the treatment and prevention of cardiovascular diseases, strokes and venous thromboembolisms. In addition to vitamin K antagonists, other oral anticoagulants have recently appeared with a more specific mechanism of action and with less apparent limitations. New anticoagulants do not require routine analytical monitoring, but do require patient follow-up by a health care professional to increase efficacy and safety and maximize adherence to therapy. The pharmacist, due to his/her expertise in pharmacology and to the success of pharmacotherapeutic monitoring programs developed in other areas such as hypertension and diabetes, is well suited for an intervention in the management and follow-up of the anticoagulated patient.Objective:This paper intends to make a contribution in the area in three aspects:1. Review existing models in other countries of pharmacotherapeutic follow-up of patients receiving oral anticoagulants.2. Create in Portugal a method to implement the pharmaceutical consultation to follow the patient under oral anticoagulation.3. Identify training needs that grant the pharmacist the necessary skills to follow the anticoagulated patient.Methods: • Research in Pubmed, and other sources considered relevant to the main topic, with the purpose of analyzing what had been published in the area. • The relevant parameters for the correct use of anticoagulants and pharmacotherapeutic follow-up of these patients were defined based on the information found and on the characteristics of each drug.• Creation of a training program structure for pharmacists. Results: A review of the anticoagulated patient follow-up models available in other countries for both anti-vitamin K drugs and non-vitamin K antagonist oral anticoagulants was undertaken. The main guidelines in the area and the recommendations of the scientific societies involved in the use of oral anticoagulants have been consulted. There have been reports of successful anticoagulation monitoring programs with impact on improving the correct use of vitamin K antagonists. These follow-up programs begin to include the new anticoagulants in their protocols.Based on the information found, a model of follow-up of these patients by the pharmacist was created with the aim of improving the efficacy and safety in the use of these drugs.Finally, based on the knowledge required of the pharmacist so that he/she can fully exert this activity, a structured training in the area of anticoagulation is proposed, which will allow him to develop these competences.Conclusion: This work allowed the creation of a pharmaceutical consultation model for the monitoring of anticoagulated patients, for future validation in the Portuguese reality.It is thus expected that this model contributes to the improvement of the control of anticoagulated patients in Portugal, in the scope of pharmaceutical consultation.