The relative risk of major gastrointestinal bleeding (GIB) among different direct oral anticoagulants (DOACs) is debatable. Randomized controlled trials (RCTs) comparing DOACs with each other are lacking. We performed network meta-analysis to assess whether the risk of major GIB differs based on type and dose of DOAC. Literature search of PubMed, EMBASE and Cochrane databases from inception to August 2019, limited to English publications, was conducted to identify RCTs comparing DOACs with warfarin or enoxaparin for any indication. Primary outcome of interest was major GIB risk. We used frequentist network meta-analysis through the random-effects model to compare DOACs with each other and DOACs by dose to isolate the impact on major GIB. Twenty-eight RCTs, including 139 587 patients receiving six anticoagulants, were selected. The risk of major GIB for DOACs was equal to warfarin. Comparison of DOACs with each other did not show risk differences. After accounting for dose, rivaroxaban 20 mg, dabigatran 300 mg and edoxaban 60 mg daily had 47, 40 and 22% higher rates of major GIB versus warfarin, respectively. Apixaban 5 mg twice daily had lower major GIB compared to dabigatran 300 mg (OR, 0.63; 95% CI, 0.44-0.88) and rivaroxaban 20 mg (OR, 0.60; 95% CI, 0.43-0.83) daily. Heterogeneity was low, and the model was consistent without publication bias (Egger's test: P = 0.079). All RCTs were high-quality with low risk of bias. DOACs at standard dose, except apixaban, had a higher risk of major GIB compared to warfarin. Apixaban had a lower rate of major GIB compared to dabigatran and rivaroxaban.

Background: Warfarin is an anticoagulant that is used for the prophylactic and therapeutic treatment for a wide range of thrombo-embolic disorders. The prescribing and monitoring of warfarin therapy is challenging due to the fact that warfarin exhibits numerous interactions with other drugs and a variety of factors that influence the dosing of warfarin. Objective: The general objective of this study was to investigate the prevalence of drugs prescribed with warfarin that may have a potential drug-drug interaction (DDI) with warfarin. Methods: This was a cross-sectional, observational or qualitative study that was conducted on medicine claims data of a pharmaceutical benefit management company for patients receiving warfarin therapy for a six year period, ranging from 1 January 2005 to 31 December 2010. Drug products that were co-prescribed with warfarin were also identified from the medicine claims database. The total number of prescriptions for all drug products during the study period were analysed and compared to the warfarin dataset. This was done by means of the SAS 9.1® computer package (SAS Institute, 2004). The total number of prescriptions and medicine items claimed from the database during the study period were respectively 49 523 818 and 118 305 941. Potential DDls between warfarin and coprescribed drugs were identified and classified according to a clinically significant rating. The clinically significance ratings of potential DDls are described in three degrees of severity, identified as major, moderate and minor (Tatro, 2011 :xiv). Results: The database consisted of 427 238 warfarin prescriptions and 427 744 warfarin medicine items, which represented 0.9% of the total number of prescriptions and 0.4% of total number of medicine items. The total number of patients who claimed warfarin prescriptions through the database represented 0.9% (n=68 575) of the total number of patients who claimed prescriptions in the total database (2005-2010). General practitioners prescribed the highest frequency of warfarin medicine items, representing 58.3% (n=249 202) of the total number prescribed. The age group that claimed the highest frequency of warfarin prescriptions (n=327 592, 76.6%) and the highest frequency of warfarin medicine items (n=327 984, 76.7%) was age group 4 (consisting of patients 59 years and older). The distribution between females and males regarding warfarin prescriptions claimed (n=205 999, 48.2%; n=221 117, 51.8%) and warfarin medicine items claimed (n=206 232, 48.2%; n=221 390, 51.8%) were almost equal. General practitioners prescribed the highest average PDD (7.01 mg ± 9.86 mg) of warfarin medicine items. Paediatric cardiologists prescribed the lowest average PDD (4.61 mg ± 1.29 mg) of warfarin medicine items. A d-value of 0.1 indicates that there is no practical difference of the average PDD between general practitioners and paediatric cardiologists. The average PDD of warfarin medicine items between females (6.60 mg ± 9.06 mg) and males (6.74 mg± 8.41 mg) was almost equal. The age group who was prescribed the highest average PDD was age group 2 (consisting of patients 20 years to 39 years old) (7.42 mg± 7.42 mg). Age group 4 (consisting of patients 59 years and older) (6.50 mg± 8.90 mg) was prescribed the lowest average PDD of warfarin medicine items. A d-value of 0.1 indicates that there is no practical difference of the average PDDs of warfarin medicine items between these two age groups. The results revealed that drugs with a significance rating (SR) of 1 (n=155 066, 43.3%), 2 (n=30128, 8.4%), 4 (n=137144, 38.3%), and 5 (n=36144, 10.1%) were co-prescribed with warfarin in the six year study period. The five drugs that was co-prescribed with warfarin most frequently was aspirin (n=48 903, 13.6%), thyroxine (n=33 954, 9.5%), amiodarone (n=25 056, 7.0%), simvastatin (n=19 070, 5.3%) and celecoxib (n=10 794, 3.0%). These five drugs have a SR of 1. Conclusions: This study showed that the top five drugs most frequently prescribed with warfarin are aspirin, thyroxine, amiodarone, simvastatin and celecoxib. These drugs can potentially interact with warfarin. The potential interactions of these drugs are rated with a significance rating of 1. This concludes that drugs that can potentially cause life threatening effects and permanent damage are commonly co-prescribed with warfarin. Clinical data concerning the INR or PT must be obtained in order to evaluate whether or not warfarin therapy is changed when a potentially interacting drug is co-prescribed. The age of the patients as well as the duration of warfarin treatment should also be obtained in order to assess whether warfarin treatment is changed with the progression of age. / MPharm (Pharmacy Practice), North-West University, Potchefstroom Campus, 2013

Background: Warfarin is an anticoagulant that is used for the prophylactic and therapeutic treatment for a wide range of thrombo-embolic disorders. The prescribing and monitoring of warfarin therapy is challenging due to the fact that warfarin exhibits numerous interactions with other drugs and a variety of factors that influence the dosing of warfarin. Objective: The general objective of this study was to investigate the prevalence of drugs prescribed with warfarin that may have a potential drug-drug interaction (DDI) with warfarin. Methods: This was a cross-sectional, observational or qualitative study that was conducted on medicine claims data of a pharmaceutical benefit management company for patients receiving warfarin therapy for a six year period, ranging from 1 January 2005 to 31 December 2010. Drug products that were co-prescribed with warfarin were also identified from the medicine claims database. The total number of prescriptions for all drug products during the study period were analysed and compared to the warfarin dataset. This was done by means of the SAS 9.1® computer package (SAS Institute, 2004). The total number of prescriptions and medicine items claimed from the database during the study period were respectively 49 523 818 and 118 305 941. Potential DDls between warfarin and coprescribed drugs were identified and classified according to a clinically significant rating. The clinically significance ratings of potential DDls are described in three degrees of severity, identified as major, moderate and minor (Tatro, 2011 :xiv). Results: The database consisted of 427 238 warfarin prescriptions and 427 744 warfarin medicine items, which represented 0.9% of the total number of prescriptions and 0.4% of total number of medicine items. The total number of patients who claimed warfarin prescriptions through the database represented 0.9% (n=68 575) of the total number of patients who claimed prescriptions in the total database (2005-2010). General practitioners prescribed the highest frequency of warfarin medicine items, representing 58.3% (n=249 202) of the total number prescribed. The age group that claimed the highest frequency of warfarin prescriptions (n=327 592, 76.6%) and the highest frequency of warfarin medicine items (n=327 984, 76.7%) was age group 4 (consisting of patients 59 years and older). The distribution between females and males regarding warfarin prescriptions claimed (n=205 999, 48.2%; n=221 117, 51.8%) and warfarin medicine items claimed (n=206 232, 48.2%; n=221 390, 51.8%) were almost equal. General practitioners prescribed the highest average PDD (7.01 mg ± 9.86 mg) of warfarin medicine items. Paediatric cardiologists prescribed the lowest average PDD (4.61 mg ± 1.29 mg) of warfarin medicine items. A d-value of 0.1 indicates that there is no practical difference of the average PDD between general practitioners and paediatric cardiologists. The average PDD of warfarin medicine items between females (6.60 mg ± 9.06 mg) and males (6.74 mg± 8.41 mg) was almost equal. The age group who was prescribed the highest average PDD was age group 2 (consisting of patients 20 years to 39 years old) (7.42 mg± 7.42 mg). Age group 4 (consisting of patients 59 years and older) (6.50 mg± 8.90 mg) was prescribed the lowest average PDD of warfarin medicine items. A d-value of 0.1 indicates that there is no practical difference of the average PDDs of warfarin medicine items between these two age groups. The results revealed that drugs with a significance rating (SR) of 1 (n=155 066, 43.3%), 2 (n=30128, 8.4%), 4 (n=137144, 38.3%), and 5 (n=36144, 10.1%) were co-prescribed with warfarin in the six year study period. The five drugs that was co-prescribed with warfarin most frequently was aspirin (n=48 903, 13.6%), thyroxine (n=33 954, 9.5%), amiodarone (n=25 056, 7.0%), simvastatin (n=19 070, 5.3%) and celecoxib (n=10 794, 3.0%). These five drugs have a SR of 1. Conclusions: This study showed that the top five drugs most frequently prescribed with warfarin are aspirin, thyroxine, amiodarone, simvastatin and celecoxib. These drugs can potentially interact with warfarin. The potential interactions of these drugs are rated with a significance rating of 1. This concludes that drugs that can potentially cause life threatening effects and permanent damage are commonly co-prescribed with warfarin. Clinical data concerning the INR or PT must be obtained in order to evaluate whether or not warfarin therapy is changed when a potentially interacting drug is co-prescribed. The age of the patients as well as the duration of warfarin treatment should also be obtained in order to assess whether warfarin treatment is changed with the progression of age. / MPharm (Pharmacy Practice), North-West University, Potchefstroom Campus, 2013

De plus en plus d’études montrent un lien entre la teneur en vitamine K (VK) dans l’organisme et la cognition. Certaines études effectuées in vitro on montré l’effet de la VK au niveau moléculaire, mais très peu in vivo. Une étude récente de Tamadon-Nejad a montré qu’un traitement de 14mg/kg/jr de warfarine, un antagoniste de la VK, administré simultanément à des injections sous-cutanées de 85mg/kg/jr de phylloquinone entrainait une diminution significative de la concentration de MK-4 du cerveau, résultant en une diminution significative du statut vitaminique K au cerveau, une altération de la cognition, du comportement exploratoire et de la locomotion [1]. Dans la présente étude, le traitement de Tamadon-Nejad a été modifié et les doses de phylloquinone ont été augmentées à 120mg/kg/jr (WVK) ce qui a maintenu une diminution significative de la concentration de la concentration de MK-4 dans le cerveau, mais a entrainé une surcompensation par la phylloquinone, résultant en une augmentation significative du statut vitaminique K au cerveau. Ce statut a été associé à une mémoire de reconnaissance intacte et corrélé à une amélioration de la mémoire spatiale des rats WVK. Le traitement a aussi été associé à une augmentation significative de l’anxiété et au rétablissement du comportement exploratoire et de la locomotion des rats WVK comparativement à l’étude de Tamadon-Nejad [1]. Dans l’hippocampe des rats WVK, l’amélioration de la cognition et le rehaussement du statut vitaminique K du cerveau n'ont pas induit de variation significative de l’activation des protéines dépendantes de la VK Gas6 et Protéine S, mais ont été associés à une augmentation significative de l’activation de la voie MAPK, à une inhibition de l’apoptose et à une présence accrue de la microglie. En somme, cette étude confirme le rôle modulateur de la VK dans le cerveau sur la cognition et la survie cellulaire. / There is growing evidence that vitamin K (VK) plays a role in cognition. Some in vitro studies have shown how VK affects different molecular pathways in brain cells, but few in vivo studies have been conducted. Recently, a study from Tamadon- Nejad showed that a treatment of 14mg/kg/d of warfarine, a VK antagonist, given simultaneously with subcutaneous injections of 85mg/kg/d lead to a significant decrease in MK-4 concentration in brain, resulting in a significant decrease of VK status in brain, and perturbation in cognition, exploratory behaviour and locomotion [1]. In the present study, we modified the treatment used in Tamadon-Nejad and increased the phylloquinone doses to 120mg/kg/d which maintained the significant decrease in MK-4 concentration in brain, but lead to an overcompensation of phylloquinone that resulted in an increase of VK status in brain. This status was associated with an intact recognition memory and correlated with an improvement in spatial memory of WVK rats. The treatment was also associated with a significant increase in anxiety and recovery of exploratory behavior and locomotion compared to rats in the Tamadon-Nejad study [1]. In WVK rat hippocampi, cognition improvement and increased VK status were not associated with significant variation in VK dependant proteins (VKDP) Gas6 and Protein S activation, but were associated with an increase in the MAPK activation pathway, an inhibition of apoptosis and, an increased presence of microglia. In summary, this study confirms the modulatory role of VK in brain in cognition and cell survival.

Estudo prospectivo e randomizado de 30 pacientes, submetidos a derivação cavopulmonar total com tubo extracardíaco. Os dados refletem o período de 2008 a 2011, com seguimento de dois anos, por meio de avaliação clínica, laboratorial, ecocardiográfica, angiotomográfica e cintilográfica. Neste estudo, procuramos comparar a eficácia do ácido acetil salicílico (AAS) e da Varfarina na profilaxia da trombose na população estudada. Para tanto, analisamos alterações nos fatores de coagulação (VII, VIII e Proteína C ); ou nos dados clínicos que predispusessem a ocorrência de trombo no pós-operatório. Além disso, no pós-operatório, após a randomização (15 pacientes randomizados para receber Varfarina, Grupo I, e 15 pacientes randomizados para receber AAS, Grupo II), estudamos a interferência da fenestração na ocorrência de trombo; alterações hemodinâmicas que pudessem contribuir com a ocorrência de trombo (fluxo lento pelo tubo extracardíaco), por meio de ecocardiograma transesofágico realizado com até 10 dias de pós operatório, 3, 6, 12 e 24 meses de pós operatório. A presença do fenômeno tromboembólico era pesquisada, além dos ecocardiogramas acima citados, por meio de consultas clínicas realizadas com a mesma periodicidade e que avaliavam, ainda, efeitos colaterais ou complicações no uso de cada uma das drogas. Avaliamos também a viabilidade e aderência ao uso de cada uma delas. O seguimento contou igualmente com a realização de angiotomografia aos 6, 12 e 24 meses de pós-operatório para avaliação de alterações na parede interna do tubo, bem como trombos e cintilografia pulmonar, ventilação-perfusão para avaliar possível tromboembolismo pulmonar. Durante o seguimento, ocorreram dois óbitos, ambos no grupo em uso de Varfarina. Ao todo, durante os dois anos de seguimento, 33,3% dos pacientes apresentaram fenômeno tromboembólico. Sendo que, entre os paciente em uso de AAS, 46,7% apresentaram tal complicação e 20% entre os pacientes em uso de Varfarina (p=0,121). Com relação a avaliação pré-operatória, a ocorrência prévia de trombo e baixos níveis de proteína C da coagulação foram os únicos fatores que influenciaram no tempo de sobrevida livre de trombo, com valores de p de 0,035 e 0,047 respectivamente. Ao final de dois anos de seguimento, na avaliação angiotomográfica, 35,7% dos pacientes em uso de AAS tinham material hiper-refringente depositado em tubo extracardíaco com espessura superior a 2mm ( p= 0,082). Já na avaliação por cintilografia de ventilação-perfusão, dois pacientes apresentaram sinais de tromboembolismo pulmonar, ambos em uso de AAS (p=0,483), e um deles com evolução desfavorável do circuito tipo Fontan. Com relação a segurança e aderência ao tratamento, cinco pacientes tiveram dificuldade de aderência (só viabilizada por tratar-se de protocolo de estudo), entre eles, quatro em uso de Varfarina e apresentando INR variando de 1 a 6,4. Para comprovação numérica, com força estatística dos dados encontrados, uma força tarefa deve ocorrer para que se consiga um grupo maior de pacientes incluídos neste estudo. No entanto, a diferença entre os dois grupos na evolução livre de trombo nos dois primeiros anos de pós-operatório não pode, e nem deve, ser ignorada / Prospective randomized trial of 30 patients who had undergone total cavopulmonary anastomosis via an extracardiac conduit. The data reflect the period between 2008 and 2011, with two-year follow-up, through clinical, laboratorial, echocardiographic, angiotomographic, and scintigraphic assessment. In this study, we aimed to compare the efficiency of ASA (Aspirin) and Warfarin in the preventive treatment of thrombosis in the tried population. For such, we\'ve analyzed changes in coagulation factors (VII, VIII and Protein C) or in the clinical data which would predispose the occurrence of postoperative thrombus. Moreover, during postoperative care, after randomization (15 patients randomly selected to be trated with Warfarin, referred to as Group I, and 15 patients randomly selected to be treated with ASA, referred to as Group II), we also studied the influence of fenestration in the occurrence of thrombus; hemodynamic variations which could contribute to the occurrence of thrombus (slow blood flow in the extracardiac conduit), with postoperative transesophageal echocardiogram being performed within 10 days, and thereafter 3, 6, 12 and 24 months. Besides the echocardiograms aforementioned, the presence of thromboembolic events was sought after by clinical appointments taking place with the same frequency, which evaluated, apart from thromboembolism, side effects or complications from the usage of each of the drugs. We\'ve also evaluated the compliance to and feasibility of each of them. Postoperative angiotomography was also performed during the follow-up, within 6, 12 and 24 months, for the evaluation of changes on the inside wall of the extracardiac conduit, as well as thrombi, and pulmonary ventilation/perfusion scintigraphy for assessment of pulmonary thromboembolism possibility. During the follow-up, two deaths were registered, both in the group being treated with Warfarin. Overall, in the two-year follow-up, 33,3% of the patients presented thromboembolic events. Among the group being treated with ASA, 46,7% presented such complication, whereas in the group being treated with Warfarin, 20% had the same complication (p=0,121). Regarding the preoperative evaluation, prior occurrence of thrombus and low levels of coagulation factor Protein C were the only variables which influenced living time without thrombus, with p-values of 0,035 and 0,047. At the end of the two-year follow-up, in the angiotomographic evaluation, 35,7% of patients treated with ASA presented material accumulation inside the extracardiac conduit, with over 2mm of thickness (p=0,082). As for the ventilation/perfusion scintigraphy, two patients presented traces of pulmonary thromboembolism, both treated with ASA (p=0,483), one of whom with unfavorable development of the Fontan circuit. Concerning safety and compliance to the treatment, five patients had difficulty to comply with the treatment (only viable for its trial nature), among those, four under treatment with Warfarin and presenting INR values ranging from 1 to 6,4. For quantitative verification, providing statistic value to the data, an effort must be made for a larger number of patients to be gathered and tried with this treatment. However, the difference in results concerning thrombus-free recovery between the two groups during the two years following surgery cannot, and must not, be ignored

Poison operations are a widely used technique for rodent control in the indigenous forests of New Zealand. This study examined the bait-take and rat monitoring data obtained for continuous poison operations at Boundary Stream Mainland Island (BSMI), Hawke’s Bay, between 1996 and 2007. Since the beginning of the Mainland Island project at BSMI in 1996, 800 ha of indigenous forest have been treated with an ‘Integrated Pest Management’ approach, in which rodents (primarily ship rats) have been targeted by consecutive ground poison operations. The aim of the intensive pest control was to allow the ecosystem to recover and provide a safe environment for threatened native bird species to recover or be re-introduced. Another important aim of this pest control is to provide experience and expert knowledge in management techniques especially applicable to the protection of indigenous habitat on the New Zealand mainland. This research study had two main aims: to identify spatial patterns of the rodent population at BSMI and to determine the efficacy of the different rodenticides applied for their control. The distribution of the rodent population was investigated by spatial analysis of bait-take across the reserve and through time. Visualisation of high and low bait-take areas revealed that there was a noticeable reinvasion from adjacent unmanaged native forests, but not markedly from exotic forest or pasture. Reinvasion from small and isolated adjacent forests ceased to be noticeable consistently after approximately four years of the poison operation, while a large scenic native reserve, as well as a narrow part of the treatment area surrounded by many native bush patches, were continuously affected by reinvasion through the entire project time. Bait-take was visibly higher after the bait had either been removed, or left in the field unserviced, over winter. No consistent areas of no bait-take were identified. Further statistical analysis of bait-take data revealed that bait-take was higher in bait stations within 150 m of the treatment edge than interior bait stations. Bait-take in broadleaf/tawa/podocarp forest was significantly higher than in kamahi/kanuka/rewarewa, beech and cloud-cap forest. The second aim of the study was to determine the efficacy of the various bait types with different active ingredients used during the operation. Rat monitoring data, namely rat tracking indices (RTI) obtained from tracking tunnels, were statistically modelled using Generalised Linear Models. Diphacinone cereal pellets (Pestoff® 50D, 0.05g/kg diphacinone) obtained the lowest RTI, followed by pindone cereal pellets (Pindone Pellets®, 0.5g/kg pindone), brodifacoum cereal pellets (Pestoff® 20p and Talon®, 0.02 g/kg brodifacoum), coumatetralyl paste (Racumin®, 0.375 g/kg) and diphacinone bait blocks (Ditrac®, 0.05 g/kg). Cereal pellet baits worked better than any other bait type used at this location. Season had no statistically significant effect on either RTI or bait-take estimates. The overall goal of the poison operation to decrease rat numbers, and to maintain low levels, has been met. However, the results of this study suggest that baiting needs to be done continuously and over the entire treatment area. Edge bait stations – particularly next to adjacent native forests – should be prioritised to target reinvading rodents. Poisons presented in cereal pellet baits should be preferred to other bait types. Both pindone and brodifacoum showed very good results, as well as diphacinone in cereal pellet baits.

This descriptive, correlational, cross-sectional study explored the relationships among the variables self-care action, self-care knowledge, and affiliated individuation and quality of life for persons on chronic warfarin therapy. This study also explored the moderating effects of self-care knowledge and affiliated individuation on quality of life. This research was guided by a theoretical framework based on modeling and role-modeling theory (Erickson, Tomlin, & Swain, 1983). The sample consisted of 83 adults between the ages of 30 to 91 years. The majority of participants were Caucasian, educated, retired and almost evenly distributed between male and female. Each subject completed the following instruments: the Oral Anticoagulation Knowledge (OAK) test, the Duke Anticoagulation Satisfaction Scale (DASS), the Basic Needs Satisfaction Inventory (BNSI), and the generic quality of life survey (SF36v2). Data was analyzed using correlation and hierarchical multiple regression analysis. Results indicated significant correlations among most of the study variables. Self-care action significantly explained variances in all but two quality of life variables. Self-care knowledge and affiliated individuation had statistically significant moderating effects on the DASS negative impact and hassles/burdens subscales. Self-care knowledge also demonstrated a significant moderating effect on the SF36v2 physical function subscale. These findings support the concepts proposed by the study's theoretical framework. This research serves as validation of Acton's (1997) study findings for the concept of affiliated individuation and its value as a self-care resource in a specific clinical population. / text

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

Einleitung: Wenn spontane Blutungsneigung zusammenkommt mit der Notwendigkeit einer gerinnungshemmenden Behandlung, so sind Blutungskomplikationen vorgezeichnet. Genau dies ist der Fall bei Patienten mit feuchter altersbedingter Makuladegeneration (AMD) und internistischen Erkrankungen wie Vorhofflimmern, Thrombosen, Embolien oder Herzklappenersatz. Im Verlauf der feuchten AMD treten typischerweise subretinale Blutungen an der Stelle des schärfsten Sehens auf. Ist die Gerinnung gehemmt, so kann sich diese spontane Makulablutung zur gefürchteten Komplikation einer subretinalen Massenblutung ausweiten, die zu einem riesigen Zentralskotom (Verlust der Sehfähigkeit im Zentrum des Gesichtsfelds) bis hin zur Erblindung führt. Mit zunehmendem Lebensalter steigt das Risiko dafür stark an, weil sowohl die AMD als auch die Indikationen für Antikoagulation mit dem Alter überproportional zunehmen. Diese Problematik wird bei der Indikationsstellung zur Antikoagulation offensichtlich zu wenig berücksichtigt. Denn in den vergangenen Jahren wurden vermehrt antikoagulierte Patienten mit massiven subretinalen Blutungen aus feuchter AMD in der Universitäts-Augenklinik Göttingen (UAKG) behandelt. Quantitative Daten zu Nutzen und Risiken der Antikoagulation aus internistischer Sicht sind ausreichend vorhanden. Quantitative Daten zur oben genannten AMD-Augenproblematik gibt es bisher nur sehr wenige.Ziel der Arbeit: Das Ziel dieser Arbeit ist es, die Risikolage zu untersuchen, um Daten für eine Nutzen-Risiko-Abwägung zwischen Überlebensvorteil durch Vitamin-K-Antagonisten und Steigerung des subretinalen Blutungsrisikos zur Verfügung zu stellen.Methode: Eine solche Untersuchung ist aus ethischen Gründen nicht als prospektive, kontrollierte Studie durchführbar. Daher wird retrospektiv auf Krankenblätter der UAKG aus der Zeit zwischen 01.01.2002 und 30.06.2008 zurückgegriffen. Die benötigten Daten wurden aus zwei Patientengruppen generiert: Das erste Kollektiv sind unselektierte, normale AMD-Fälle. Es handelt sich um 148 Augen von 110 Patienten, die aus den 1600 AMD-Datensätzen des Fotolabors ausgelost wurden. Alle Krankenblätter und Original-Fundusfotos wurden hinsichtlich Dauer der feuchten AMD, Blutung, Blutungsgröße und Medikamentenanamnese ausgewertet. Daraus lässt sich das inhärente Blutungsrisiko der feuchten AMD einschließlich dessen Schwere und zeitlichen Ablaufs ableiten. Weiter informiert dieses Kollektiv über die Häufigkeit von Antikoagulation bei AMD-Patienten. Das zweite Kollektiv sind Augen mit subretinaler AMD-Blutung. Diese wurden aus der Datenbank des Schwerpunktes Netzhaut-und Glaskörperchirurgie entnommen, welche alle dort behandelten Patienten ausführlich dokumentiert. Es handelte sich um 124 Augen mit subretinaler Blutung von 101 Patienten. Die zugehörigen Krankenakten wurden in derselben Weise ausgewertet. Diese Gruppe informiert über die Häufigkeit der Antikoagulation und die Blutungsschwere bei Blutungsaugen. Aus dem Verhältnis der Antikoagulationshäufigkeit bei AMD-Augen mit subretinaler Blutung zu der Antikoagulationshäufigkeit normaler AMD-Patienten folgt daraus die gesuchte Risiko-Erhöhung für Blutung unter Antikoagulation.Ergebnisse: 1. Das spontane Blutungsrisiko aus feuchter AMD liegt zwischen 16% und 25% für zwei Jahre und zwischen 25% und 64% für fünf Jahre. 2. Antikoagulation mit Vitamin-K-Antagonisten erhöht das Blutungsrisiko mindestens um das 2,3 bis 3,8 fache. 3. Die schwerste Komplikation der Blutung bei feuchter AMD, nämlich Durchbruch in den Glaskörperraum und vollständige Erblindung des Auges, tritt in 6% der spontanen AMD-Blutungen ein. Unter Vitamin-K-Antagonisten ist dies 3,5mal häufiger (21%). 4. Spontane AMD-Blutungen (ohne Gerinnungshemmung) haben einen mittleren Durchmesser von ca. 30°. Die dadurch verursachte Netzhautschädigung hat eine Ausdehnung von 27 Papillenflächen. Unter Vitamin-K-Antagonisten ist der Blutungsdurchmesser doppelt so groß, die zerstörte Netzhautfläche hat mit 109 Papillenflächen nahezu die vierfache Größe. 5. Thrombozytenaggregationshemmer führen ebenfalls zu einer Vergrößerung der subretinalen Blutung aus feuchter AMD. Die Effekte sind etwa halb so groß wie die unter Vitamin-K-Antagonisten.Diskussion: Nach diesen Ergebnissen stellt die feuchte AMD eine bisher zu gering beachtete Kontraindikation für den Einsatz von Vitamin-K-Antagonisten dar. Die Antikoagulation bei feuchter AMD erfordert eine gemeinsame Abwägung durch Internist, Augenarzt und Patient. Dabei können folgende Überlegungen als Richtschnur gelten: 1. Bei Erkrankungen mit hohem vitalen Risiko und nachgewiesenem großen Nutzen der Antikoagulation ist das höhere subretinale Blutungsrisiko der feuchten AMD ein sekundäres Argument und muss in Kauf genommen werden. Dazu gehören Lungenembolie, Vorhofflimmern mit hohem CHA2DS2VASc-Score, bzw. CHADS2-Score oder mechanischer Herzklappenersatz. 2. Bei Erkrankungen mit niedrigem vitalem Risiko und fraglichem Nutzen der Vitamin-K-Antagonisierung überwiegt das Erblindungsrisiko der AMD-Augen in der Risikoabwägung. Die Antikoagulation sollte unterbleiben. Dazu gehören Vorhofflimmern mit niedrigem CHA2DS2VASc-Score, bzw. CHADS2-Score sowie biologischer Klappenersatz. 3. Die Indikationen zwischen diesen Extremen bedürfen einer ausgiebigen Aufklärung und Entscheidungsfindung zusammen mit dem betroffenen Patienten.

Estudo prospectivo e randomizado de 30 pacientes, submetidos a derivação cavopulmonar total com tubo extracardíaco. Os dados refletem o período de 2008 a 2011, com seguimento de dois anos, por meio de avaliação clínica, laboratorial, ecocardiográfica, angiotomográfica e cintilográfica. Neste estudo, procuramos comparar a eficácia do ácido acetil salicílico (AAS) e da Varfarina na profilaxia da trombose na população estudada. Para tanto, analisamos alterações nos fatores de coagulação (VII, VIII e Proteína C ); ou nos dados clínicos que predispusessem a ocorrência de trombo no pós-operatório. Além disso, no pós-operatório, após a randomização (15 pacientes randomizados para receber Varfarina, Grupo I, e 15 pacientes randomizados para receber AAS, Grupo II), estudamos a interferência da fenestração na ocorrência de trombo; alterações hemodinâmicas que pudessem contribuir com a ocorrência de trombo (fluxo lento pelo tubo extracardíaco), por meio de ecocardiograma transesofágico realizado com até 10 dias de pós operatório, 3, 6, 12 e 24 meses de pós operatório. A presença do fenômeno tromboembólico era pesquisada, além dos ecocardiogramas acima citados, por meio de consultas clínicas realizadas com a mesma periodicidade e que avaliavam, ainda, efeitos colaterais ou complicações no uso de cada uma das drogas. Avaliamos também a viabilidade e aderência ao uso de cada uma delas. O seguimento contou igualmente com a realização de angiotomografia aos 6, 12 e 24 meses de pós-operatório para avaliação de alterações na parede interna do tubo, bem como trombos e cintilografia pulmonar, ventilação-perfusão para avaliar possível tromboembolismo pulmonar. Durante o seguimento, ocorreram dois óbitos, ambos no grupo em uso de Varfarina. Ao todo, durante os dois anos de seguimento, 33,3% dos pacientes apresentaram fenômeno tromboembólico. Sendo que, entre os paciente em uso de AAS, 46,7% apresentaram tal complicação e 20% entre os pacientes em uso de Varfarina (p=0,121). Com relação a avaliação pré-operatória, a ocorrência prévia de trombo e baixos níveis de proteína C da coagulação foram os únicos fatores que influenciaram no tempo de sobrevida livre de trombo, com valores de p de 0,035 e 0,047 respectivamente. Ao final de dois anos de seguimento, na avaliação angiotomográfica, 35,7% dos pacientes em uso de AAS tinham material hiper-refringente depositado em tubo extracardíaco com espessura superior a 2mm ( p= 0,082). Já na avaliação por cintilografia de ventilação-perfusão, dois pacientes apresentaram sinais de tromboembolismo pulmonar, ambos em uso de AAS (p=0,483), e um deles com evolução desfavorável do circuito tipo Fontan. Com relação a segurança e aderência ao tratamento, cinco pacientes tiveram dificuldade de aderência (só viabilizada por tratar-se de protocolo de estudo), entre eles, quatro em uso de Varfarina e apresentando INR variando de 1 a 6,4. Para comprovação numérica, com força estatística dos dados encontrados, uma força tarefa deve ocorrer para que se consiga um grupo maior de pacientes incluídos neste estudo. No entanto, a diferença entre os dois grupos na evolução livre de trombo nos dois primeiros anos de pós-operatório não pode, e nem deve, ser ignorada / Prospective randomized trial of 30 patients who had undergone total cavopulmonary anastomosis via an extracardiac conduit. The data reflect the period between 2008 and 2011, with two-year follow-up, through clinical, laboratorial, echocardiographic, angiotomographic, and scintigraphic assessment. In this study, we aimed to compare the efficiency of ASA (Aspirin) and Warfarin in the preventive treatment of thrombosis in the tried population. For such, we\'ve analyzed changes in coagulation factors (VII, VIII and Protein C) or in the clinical data which would predispose the occurrence of postoperative thrombus. Moreover, during postoperative care, after randomization (15 patients randomly selected to be trated with Warfarin, referred to as Group I, and 15 patients randomly selected to be treated with ASA, referred to as Group II), we also studied the influence of fenestration in the occurrence of thrombus; hemodynamic variations which could contribute to the occurrence of thrombus (slow blood flow in the extracardiac conduit), with postoperative transesophageal echocardiogram being performed within 10 days, and thereafter 3, 6, 12 and 24 months. Besides the echocardiograms aforementioned, the presence of thromboembolic events was sought after by clinical appointments taking place with the same frequency, which evaluated, apart from thromboembolism, side effects or complications from the usage of each of the drugs. We\'ve also evaluated the compliance to and feasibility of each of them. Postoperative angiotomography was also performed during the follow-up, within 6, 12 and 24 months, for the evaluation of changes on the inside wall of the extracardiac conduit, as well as thrombi, and pulmonary ventilation/perfusion scintigraphy for assessment of pulmonary thromboembolism possibility. During the follow-up, two deaths were registered, both in the group being treated with Warfarin. Overall, in the two-year follow-up, 33,3% of the patients presented thromboembolic events. Among the group being treated with ASA, 46,7% presented such complication, whereas in the group being treated with Warfarin, 20% had the same complication (p=0,121). Regarding the preoperative evaluation, prior occurrence of thrombus and low levels of coagulation factor Protein C were the only variables which influenced living time without thrombus, with p-values of 0,035 and 0,047. At the end of the two-year follow-up, in the angiotomographic evaluation, 35,7% of patients treated with ASA presented material accumulation inside the extracardiac conduit, with over 2mm of thickness (p=0,082). As for the ventilation/perfusion scintigraphy, two patients presented traces of pulmonary thromboembolism, both treated with ASA (p=0,483), one of whom with unfavorable development of the Fontan circuit. Concerning safety and compliance to the treatment, five patients had difficulty to comply with the treatment (only viable for its trial nature), among those, four under treatment with Warfarin and presenting INR values ranging from 1 to 6,4. For quantitative verification, providing statistic value to the data, an effort must be made for a larger number of patients to be gathered and tried with this treatment. However, the difference in results concerning thrombus-free recovery between the two groups during the two years following surgery cannot, and must not, be ignored