Relation of psychological distress to the INR in Patients with venous thromboembolism with and without oral anticoagulant therapy

Psychological distress might affect the international normalized ratio (INR), but effects might vary depending on oral anticoagulant (OAC) therapy.

TRial of an Educational intervention on patients' knowledge of Atrial fibrillation and anticoagulant therapy, INR control, and outcome of Treatment with warfarin (TREAT)

Background Atrial fibrillation (AF) patients with a high risk of stroke are recommended anticoagulation with warfarin. However, the benefit of warfarin is dependent upon time spent within the target therapeutic range (TTR) of their international normalised ratio (INR) (2.0 to 3.0). AF patients possess limited knowledge of their disease and warfarin treatment and this can impact on INR control. Education can improve patients' understanding of warfarin therapy and factors which affect INR control. Methods/Design Randomised controlled trial of an intensive educational intervention will consist of group sessions (between 2-8 patients) containing standardised information about the risks and benefits associated with OAC therapy, lifestyle interactions and the importance of monitoring and control of their International Normalised Ratio (INR). Information will be presented within an 'expert-patient' focussed DVD, revised educational booklet and patient worksheets. 200 warfarin-naïve patients who are eligible for warfarin will be randomised to either the intervention or usual care groups. All patients must have ECG-documented AF and be eligible for warfarin (according to the NICE AF guidelines). Exclusion criteria include: aged < 18 years old, contraindication(s) to warfarin, history of warfarin USE, valvular heart disease, cognitive impairment, are unable to speak/read English and disease likely to cause death within 12 months. Primary endpoint is time spent in TTR. Secondary endpoints include measures of quality of life (AF-QoL-18), anxiety and depression (HADS), knowledge of AF and anticoagulation, beliefs about medication (BMQ) and illness representations (IPQ-R). Clinical outcomes, including bleeding, stroke and interruption to anticoagulation will be recorded. All outcome measures will be assessed at baseline and 1, 2, 6 and 12 months post-intervention. Discussion More data is needed on the clinical benefit of educational intervention with AF patients receiving warfarin. Trial registration ISRCTN93952605

Educational and behavioural interventions for anticoagulant therapy in patients with atrial fibrillation

Background Current guidelines recommend oral anticoagulation therapy for patients with atrial fibrillation who are at moderate-to-high risk of stroke, however anticoagulation control (time in therapeutic range (TTR)) is dependent on many factors. Educational and behavioural interventions may impact on patients’ ability to maintain their International Normalised Ratio (INR) control. Objectives To evaluate the effects on TTR of educational and behavioural interventions for oral anticoagulation therapy (OAT) in patients with atrial fibrillation (AF). Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) in The Cochrane Library (2012, Issue 7 of 12), MEDLINE Ovid (1950 to week 4 July 2012), EMBASE Classic + EMBASE Ovid (1947 to Week 31 2012), PsycINFO Ovid (1806 to 2012 week 5 July) on 8 August 2012 and CINAHL Plus with Full Text EBSCO (to August 2012) on 9 August 2012. We applied no language restrictions. Selection criteria The primary outcome analysed was TTR. Secondary outcomes included decision conflict (patient's uncertainty in making health-related decisions), percentage of INRs in the therapeutic range, major bleeding, stroke and thromboembolic events, patient knowledge, patient satisfaction, quality of life (QoL), and anxiety. Data collection and analysis The two review authors independently extracted data. Where insufficient data were present to conduct a meta-analysis, effect sizes and confidence intervals (CIs) of the included studies were reported. Data were pooled for two outcomes, TTR and decision conflict. Main results Eight trials with a total of 1215 AF patients (number of AF participants included in the individual trials ranging from 14 to 434) were included within the review. Studies included education, decision aids, and self-monitoring plus education. For the primary outcome of TTR, data for the AF participants in two self-monitoring plus education trials were pooled and did not favour self-monitoring plus education or usual care in improving TTR, with a mean difference of 6.31 (95% CI -5.63 to 18.25). For the secondary outcome of decision conflict, data from two decision aid trials favoured usual care over the decision aid in terms of reducing decision conflict, with a mean difference of -0.1 (95% CI -0.2 to -0.02). Authors' conclusions This review demonstrated that there is insufficient evidence to draw definitive conclusions regarding the impact of educational or behavioural interventions on TTR in AF patients receiving OAT. Thus, more trials are needed to examine the impact of interventions on anticoagulation control in AF patients and the mechanisms by which they are successful. It is also important to explore the psychological implications for patients suffering from this long-term chronic condition.

Patients’ and health professionals’ views and experiences of atrial fibrillation and oral-anticoagulant therapy:a qualitative meta-synthesis

Objective - Atrial fibrillation (AF) patients are prescribed oral-anticoagulant (OAC) therapy, often warfarin, to reduce stroke risk. We explored existing qualitative evidence about patients’ and health professionals’ experiences of OAC therapy. Methods - Systematic searches of eight bibliographic databases were conducted. Quality was appraised using the Critical Appraisal Skills Programme tool and data from ten studies were synthesised qualitatively. Results - Four third-order constructs, emerged from the final step in the analysis process: (1) diagnosing AF and the communication of information, (2) deciding on OAC therapy, (3) challenges revolving around patient issues, and (4) healthcare challenges. Synthesis uncovered perspectives that could not be achieved through individual studies. Conclusion - Physicians’ and patients’ experiences present a dichotomy of opinion on decision-making, which requires further exploration and changes in practice. Outcomes of workload pressure on both health professionals and patients should be investigated. The need for on-going support and education to patients and physicians is critical to achieve best practice and treatment adherence. Practice implications - Such research could encourage health professionals to understand and attend better to the needs and concerns of the patient. Additionally these findings can be used to inform researchers and healthcare providers in developing educational interventions with both patients and health professionals.

Educational and behavioural interventions for anticoagulant therapy in patients with atrial fibrillation

background Current guidelines recommend oral anticoagulation therapy for patients with atrial fibrillation who are at moderate-to-high risk of stroke, however anticoagulation control (time in therapeutic range (TTR)) is dependent on many factors. Educational and behavioural interventions may impact on patients’ ability to maintain their International Normalised Ratio (INR) control. Objectives To evaluate the effects on TTR of educational and behavioural interventions for oral anticoagulation therapy (OAT) in patients with atrial fibrillation (AF). Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) in The Cochrane Library (2012, Issue 7 of 12), MEDLINE Ovid (1950 to week 4 July 2012), EMBASE Classic + EMBASE Ovid (1947 to Week 31 2012), PsycINFO Ovid (1806 to 2012 week 5 July) on 8 August 2012 and CINAHL Plus with Full Text EBSCO (to August 2012) on 9 August 2012. We applied no language restrictions. Selection criteria The primary outcome analysed was TTR. Secondary outcomes included decision conflict (patient's uncertainty in making health-related decisions), percentage of INRs in the therapeutic range, major bleeding, stroke and thromboembolic events, patient knowledge, patient satisfaction, quality of life (QoL), and anxiety. Data collection and analysis The two review authors independently extracted data. Where insufficient data were present to conduct a meta-analysis, effect sizes and confidence intervals (CIs) of the included studies were reported. Data were pooled for two outcomes, TTR and decision conflict. Main results Eight trials with a total of 1215 AF patients (number of AF participants included in the individual trials ranging from 14 to 434) were included within the review. Studies included education, decision aids, and self-monitoring plus education. For the primary outcome of TTR, data for the AF participants in two self-monitoring plus education trials were pooled and did not favour self-monitoring plus education or usual care in improving TTR, with a mean difference of 6.31 (95% CI -5.63 to 18.25). For the secondary outcome of decision conflict, data from two decision aid trials favoured usual care over the decision aid in terms of reducing decision conflict, with a mean difference of -0.1 (95% CI -0.2 to -0.02). Authors' conclusions This review demonstrated that there is insufficient evidence to draw definitive conclusions regarding the impact of educational or behavioural interventions on TTR in AF patients receiving OAT. Thus, more trials are needed to examine the impact of interventions on anticoagulation control in AF patients and the mechanisms by which they are successful. It is also important to explore the psychological implications for patients suffering from this long-term chronic condition.

Empowerment through education : enhancing quality of life of clients on anticoagulant therapy

This particular study was a sub-study of an on-going investigation by Porter and Kazcaraba (1994) at the Veterans Administration Medical Center in Miami. While the Porter and Kazcaraba study utilizes multiple measures to determine the impact of nurse patient collaborative care on quality of life of cardiovascular patients receiving anticoagulant therapy, this study sought to find whether health education could empower similar clients to improve their quality of life. A health education program based on Freire's belief that shared collective knowledge empowers individuals to improve their lives and their community and Porter's nurse patient collaborative care model was used. Findings on a sample of thirty-eight subjects revealed strong correlations between self-esteem and life satisfaction as well as a trend towards increased power post-treatment. No group comparisons were made at posttest because the sample size was too small for meaningful statistical analysis.

Scores to predict major bleeding risk during oral anticoagulation therapy: a prospective validation study.

BACKGROUND: Clinical scores may help physicians to better assess the individual risk/benefit of oral anticoagulant therapy. We aimed to externally validate and compare the prognostic performance of 7 clinical prediction scores for major bleeding events during oral anticoagulation therapy. METHODS: We followed 515 adult patients taking oral anticoagulants to measure the first major bleeding event over a 12-month follow-up period. The performance of each score to predict the risk of major bleeding and the physician's subjective assessment of bleeding risk were compared with the C statistic. RESULTS: The cumulative incidence of a first major bleeding event during follow-up was 6.8% (35/515). According to the 7 scoring systems, the proportions of major bleeding ranged from 3.0% to 5.7% for low-risk, 6.7% to 9.9% for intermediate-risk, and 7.4% to 15.4% for high-risk patients. The overall predictive accuracy of the scores was poor, with the C statistic ranging from 0.54 to 0.61 and not significantly different from each other (P=.84). Only the Anticoagulation and Risk Factors in Atrial Fibrillation score performed slightly better than would be expected by chance (C statistic, 0.61; 95% confidence interval, 0.52-0.70). The performance of the scores was not statistically better than physicians' subjective risk assessments (C statistic, 0.55; P=.94). CONCLUSION: The performance of 7 clinical scoring systems in predicting major bleeding events in patients receiving oral anticoagulation therapy was poor and not better than physicians' subjective assessments.

Scores to predict major bleeding risk during oral anticoagulation therapy: a prospective validation study

Clinical scores may help physicians to better assess the individual risk/benefit of oral anticoagulant therapy. We aimed to externally validate and compare the prognostic performance of 7 clinical prediction scores for major bleeding events during oral anticoagulation therapy.

Advancing age and bleeding risk are the strongest barriers to anticoagulant prescription in atrial fibrillation

In clinical practice many patients with atrial fibrillation (AF) at high thromboembolic risk fail to receive adequate oral anticoagulation (OAC) [1]. The complex management of anticoagulant therapy [frequent international normalised ratio (INR) monitoring because of narrow therapeutic window, interaction with food and alcohol, concomitant medications and comorbities], the overestimation of bleeding risk and the underestimation of stroke risk, may partially explain physicians' reluctance to prescribe anticoagulation. In the current issue of Age and Ageing, Pugh and Mead [2] report a systematic review on physicians' attitudes concerning anticoagulant treatment among AF patients. Through surveys (questionnaire, clinical vignette and interview) on hypothetical case scenarios, they have identified the barriers to effective anticoagulant prescription, as follows: increasing age, bleeding risk or previous bleeding, fall risk, co-morbidities (e.g. chronic alcoholism or cognitive impairment) and lack of compliance. In particular, advanced age has been reported as the most striking reason for with-holding anticoagulation, while risk of falls and previous bleeding are also disproportionate barriers to warfarin prescription.

Variability in the international normalised ratio (INR) in patients with antiphospholipid syndrome and positive lupus anticoagulant: should the INR targets be higher?

El síndrome antifosfolípido es un desorden autoinmune caracterizado por hipercoagulabilidad que requiere terapia anticoagulante como pilar fundamental, siendo la warfarina el tratamiento de elección en los casos que requieren manejo por largos periodos. Sin embargo, los pacientes con anticoagulante lúpico positivo representan un reto porque tienen mayor riesgo de presentar eventos trombóticos, sumado a que el seguimiento con el International Normalized Ratio (INR) no es confiable, ya que estos anticuerpos generan interferencia con las pruebas de laboratorio basadas en fosfolípidos, como es el caso del tiempo de protrombina (PT) con INR basal prolongado, incluso antes del inicio de la terapia anticoagulante. Por tal razón, se ilustra el caso de una paciente con síndrome antifosfolípido primario y anticoagulante lúpico positivo quien ha presentado múltiples episodios trombóticos, a pesar de recibir terapia anticoagulante. Además se hace una revisión de la literatura disponible y se postulan nuevas metas de INR en estos pacientes diferentes de las que se plantean actualmente.

Relação da doença periodontal com a anticoagulação oral e os benefícios do tratamento periodontal em pacientes anticoagulados

Anticoagulantes orais são amplamente indicados para prevenção de eventos tromboembólicos. No entanto, nem sempre os pacientes atingem a faixa terapêutica recomendada. Os objetivos desse estudo foram avaliar a associação entre periodontite e níveis de anticoagulação (fase 1) e o efeito do tratamento periodontal nos níveis de anticoagulação (fase 2) em pacientes que faziam uso do anticoagulante oral varfarina. O exame clínico incluiu índice CPO-D, índice de placa, sangramento à sondagem, profundidade de bolsa e nível de inserção clínica. Coeficiente normalizado internacional (INR), níveis de albumina, proteína C-reativa (PCR) e fibrinogênio foram avaliados no dia zero e até 180 dias após tratamento periodontal. Na fase 1 do estudo foram examinados 62 pacientes (42 mulheres e 20 homens, com idade média de 50,8 9,2 anos). Observamos uma correlação negativa entre extensão e severidade da doença periodontal e índice de placa com valores de INR. Não houve associação entre diagnóstico periodontal e níveis de anticoagulação. Dentre os pacientes fora do alvo terapêutico, 87% apresentavam diagnóstico de periodontite, enquanto no grupo na faixa terapêutica apenas 56%. Participaram da fase 2 do estudo 26 pacientes com periodontite severa (15 mulheres e 11 homens, com idade média de 51,3 9,2 anos). O tratamento periodontal resultou em melhora significativa de todos os parâmetros periodontais e dos níveis de anticoagulação 30, 60 90 e 180 dias após conclusão da terapia periodontal. Não houve alteração significativa na dose semanal da varfarina. Foi observada redução significativa entre níveis séricos de albumina dos dia 90 e 180 após a terapia periodontal, quando comparado aos valores do dia 0 (p < 0,05). De acordo com o alvo terapêutico estabelecido, observamos que no dia 0 doze pacientes (46,15%) estavam fora dessa faixa. Esse percentual foi reduzido significativamente após tratamento periodontal, sendo 26,1% e 29,2% nos dias 60 e 90, respectivamente. Embora tenha ocorrido melhora nos níveis de anticoagulação, não houve alteração significativa nos níveis de PCR e fibrinogênio. Sendo assim, pacientes com periodontite severa podem apresentar dificuldade para atingir a faixa terapêutica e o tratamento periodontal pode resultar em benefícios na busca da anticoagulação plena. Novos estudos são necessários para avaliar se formas menos severas de doença periodontal também podem interferir com a varfarina.

Cirurgia oral em hipocoagulados

Monografia apresentada à Universidade Fernando Pessoa para obtenção do grau de Licenciado em Medicina Dentária

A Quantitative and Mechanistic Assessment of Activated Thrombin-Activatable Fibrinolysis Inhibitor and its Role in Pathological Bleeding and Thrombosis

The coagulation and fibrinolytic systems are linked by the thrombin-thrombomodulin complex which regulates each system through activation of protein C and TAFI, respectively. We have used novel assays and techniques to study the enzymology and biochemistry of TAFI and TAFIa, to measure TAFI activation in hemophilia A and protein C deficiency and to determine if enhancing TAFI activation can improve hemostasis in hemophilic plasma and whole blood. We show that TAFIa not TAFI attenuates fibrinolysis in vitro and this is supported by a relatively high catalytic efficiency (16.41μM-1s-1) of plasminogen binding site removal from fibrin degradation products (FDPs) by TAFIa. Since the catalytic efficiency of TAFIa in removing these sites is ~60-fold higher than that for inflammatory mediators such as bradykinin it is likely that FDPs are a physiological substrate of TAFIa. The high catalytic efficiency is primarily a result of a low Km which can be explained by a novel mechanism where TAFIa forms a binary complex with plasminogen and is recruited to the surface of FDPs. The low Km also suggests that TAFIa would effectively cleave lysines from FDPs during the early stages of fibrinolysis (i.e. at low concentrations of FDPs). Since individuals with hemophilia suffer from premature fibrinolysis as a result of insufficient TAFI activation we quantified TAFI activation in whole blood from hemophilic subjects. Both the rate of activation and the area under the TAFI activation time course (termed TAFIa potential) was determined to be reduced in hemophilia A and the TAFIa potential was significantly and inversely correlated with the clinical bleeding iii phenotype. Using a novel therapeutic strategy, we used soluble thrombomodulin to increase TAFI activation which improved the clot lysis time in factor VIII deficient human plasma and hemophilic dog plasma as well as hemophilic dog blood. Finally, we briefly show in a biochemical case study that TAFI activation is enhanced in protein C deficiency and when afflicted individuals are placed on Warfarin anticoagulant therapy, TAFI activation is reduced. Since TAFIa stabilizes blood clots, this suggests that reducing TAFI activation or inhibiting TAFIa may help restore blood flow in vessels with pathological thrombosis.