Minor bleeding in patients with atrial fibrillation using a non-vitamin K antagonist oral anticoagulant

Aims: We sought to investigate the magnitude of minor bleeding and identify risk factors for minor bleeds during non-vitamin K antagonist oral anticoagulant (NOAC) therapy.Methods: This was an observational cohort study of patients with atrial fibrillation (AF) referred to a regional NOAC outpatient clinic between February 2013 and October 2017. The study population consisted of 875 consecutive patients with AF who visited the NOAC outpatient unit to initiate treatment with apixaban (N = 303), dabigatran (N = 267) or rivaroxaban (N = 305) for long-term ischemic stroke prophylaxis. Minor bleed was defined as every overt bleeding that does not fulfil the criteria of major or non-major clinically relevant bleeding according to the International Society on Thrombosis and Haemostasis.Results: Overall rate of minor bleeds was 19.2 per 100 patient years of follow up. Bleeding rates for apixaban, dabigatran and rivaroxaban were 26, 8.3 and 23 per 100 patient-years of follow-up. Next to the type of NOAC, the main risk indicators for minor bleedings during NOAC therapy were a HAS-BLED score of 3 or higher and novel anticoagulant use (no history of vitamin K antagonist use).Limitation: This was a retrospective observational study evaluating NOAC treatment in a non-randomized setting.Conclusion: Our data showed that minor bleeds are common in novel NOAC users, especially when using apixaban and rivaroxaban. In the latter two NOACs, hematoma (bruises) and nose bleeds were more frequently observed and accounted for the difference with dabigatran. Besides type of NOAC, a higher HAS-BLED score and novel anticoagulant drug use were associated with an increased risk of minor bleeding

An easy-to-use tool to flag patients at risk of poor INR control:A streak of subtherapeutic INRs

Introduction: Vitamin K antagonist therapy is safest and most effective with a high time within the therapeutic range (TTR). The TTR is difficult to calculate in the consultation room, therefore physicians need an easier-to-use tool to predict poor VKA control. We explored the prognostic value of subtherapeutic INRs on future TTR in two settings: (1) Clinical review setting, where a physician (bi) annually reviews a patient and uses the INRs since the last visit to predict the TTR up to the next visit; (2) Day-to-day INR management setting, where every new INR measurement prompts a new prediction over the next 90 days. Materials and methods: Retrospective cohort of 17,711 patients from a dedicated thrombosis service, using acenocoumarol (target range 2.0-3.0), with a "streak" defined as four consecutive INRs (1) Odds ratios of any streak in the last 180 days or 1 year on a TTR <45% over the same period in the future; (2) Odds ratio of a current streak on a TTR <45% over the next 90 days. Results and conclusions: Clinical review setting: The occurrence of any streak in the last 180 days or 1 year increased the odds of a TTR <45%: ORs 2.84 (95% CI 2.41-3.34) and 3.25 (95% CI 2.72-3.87), respectively. Day-to-day INR management setting: A current streak increases the odds of poor TTR over the next 90 days 3.58 (95% CI 2.64-4.87) fold. We conclude that a streak of four consecutive subtherapeutic INRs can aid physicians in flagging at-risk patients

Reasons for discontinuation of novel oral anticoagulant therapy in patients with atrial fibrillation

Aims: We sought to investigate the reasons for, and rates of, novel oral anticoagulant (DOAC) therapy discontinuation.Methods: This was an observational cohort study of patients with atrial fibrillation (AF) referred to a regional DOAC outpatient clinic between February 2013 and October 2017. The study population consisted of 875 consecutive patients with AF who visited the DOAC outpatient unit to initiate treatment with apixaban (N = 303), dabigatran (N = 267) or rivaroxaban (N = 305) for long-term ischemic stroke prophylaxis. All the patients came from the Leeuwarden Medical Center cardiology outpatient clinic, which offers a well structured and nurse-run DOAC unit in cooperation with the hospital's thrombosis service. This clinic operates according to the Dutch nationwide guidelines on integration of anticoagulation services.Results: Overall rate of discontinuation was 11.9 per 100 patient-years of follow-up. Discontinuation rates for apixaban, dabigatran and rivaroxaban were 8.1, 16.6 and 11.5 per 100 patient-years of follow-up.Apixaban had the lowest rate of discontinuation during the 36 month follow-up period. Dabigatran and rivaroxaban had high discontinuation rates during the 3-6 month period following DOAC therapy initiation. The main reasons for discontinuation of DOAC therapy were adverse side effects, patient-initiated discontinuation and any bleed.Limitation: This was a retrospective and non-randomized study, and our results should be interpreted in light of these observations.Conclusion: DOAC discontinuation rates varied significantly and appeared related to drug-specific side effects, patient-initiated discontinuation and bleeding. We observed longer-term administration of apixaban, suggesting that this drug is better tolerated than dabigatran or rivaroxaban

Patterns of transfusion burden in an unselected population of patients with myelodysplastic syndromes:A population-based study

BACKGROUND: Ineffective hematopoiesis in patients with myelodysplastic syndromes (MDS) often results in transfusion dependence. The burden of frequent transfusions in the real-world MDS population is largely unknown.STUDY DESIGN AND METHODS: An observational, retrospective, population-based study, using the HemoBase registry, was performed including all patients diagnosed with MDS between 2005 and 2017 in Friesland, a province in the Netherlands with approximately 650,000 inhabitants. Detailed clinical information was collected from the electronic health records. Transfusion burden was classified according to the International Working Group 2018 criteria: not transfusion dependent, low (LTB), or high transfusion burden (HTB). Univariate and multivariable regression analyses were performed.RESULTS: Of 292 patients, 136 (46.6%) had a HTB of ≥8 units/16 weeks and 17 (5.8%) had a LTB of 3-7 units/16 weeks. This was present in all types of MDS patients, but patients aged 75-84 years (odds ratio [OR] 4.02, 95% confidence interval [CI]: 1.84-8.82), high-risk MDS patients (OR 2.88, 95% CI: 1.08-7.68) and MDS-EB-2 patients (OR 7.07, 95% CI: 2.17-22.90) were particularly at risk for a HTB.DISCUSSION: This study provides a reliable estimate of the transfusion burden in real-world MDS patients, with almost half of the patients having a HTB. A HTB was observed in all MDS subtypes and both low- and high-risk MDS. Therefore, we conclude that the entire MDS population might benefit from novel agents that reduce the transfusion need and that might have beneficial effects on patient outcomes and healthcare utilization outcomes.</p

Is the time in therapeutic range on coumarins predicted by previous time in therapeutic range?

Background The benefit of vitamin K antagonists depends on the time within the therapeutic range (TTR). A patient's previous TTR could be a factor in the decision to change the anticoagulation regimen. However, the predictive value of a previous TTR for a future TTR is not well established, nor is it clear which TTR should prompt action. Objectives To investigate the predictive performance of a TTR and identify a threshold below which no recovery of TTR should be expected. Patients/Methods From 18 031 patients who used acenocoumarol in a first-line anticoagulation clinic, a TTR was calculated over multiple periods of 90, 180, and 365 days each. We assessed the correlation between baseline and later TTR and the separation between groups by quintile of baseline TTR. We describe the proportion of patients who obtain a TTR >= 70% conditional on baseline TTR. Results The correlation between baseline and later TTR was 0.25 (95% confidence interval [CI], 0.24-0.26), 0.27 (95% CI, 0.26-0.28) and 0.34 (95% CI, 0.32-0.35) for analyses over 90, 180, and 365 days. Corresponding c statistics for discrimination by baseline group were 0.60, 0.61, and 0.63. The probability to obtain a TTR >= 70% increased with baseline TTR: from 42% with a baseline TTR of 50%-65% when TTR was 100% (TTR calculated over 180 days). Conclusions We conclude that a current TTR hardly predicts a future TTR. Physicians and patients should deliberate together which probabilities to accept, take measures to improve TTR, and consider potential alternatives

Costs of minor bleeds in atrial fibrillation patients using a non-vitamin K antagonist oral anticoagulant

BACKGROUND: A very common side effect of non-vitamin K antagonist oral anticoagulant (NOAC) is (minor) bleeding. Data about impact and costs of minor bleeds in NOAC therapy is still limited or not present in current literature. In this patient orientated study, we aim to provide an estimate of the costs of minor bleeds in patients with atrial fibrillation (AF) treated with a NOAC. METHODS: A retrospective observational cohort study was conducted. Patients with AF and on NOAC therapy were included. Data was obtained by questionnaires and information from electronic patient records. Reference prices were used to calculate the costs per patient. Furthermore, cost of minor bleeds per patient is compared with literature-based costs of minor and major bleeding. RESULTS: 139 patients were included. A total of 94 minor bleed were reported by 71 patients. The sum of minor bleeding costs from societal perspective were €9,851.49, or on average €70,87 (95% CI €54,37 - €85,68) per patient with AF. The biggest cost drivers were rectal and vaginal bleeds, epistaxis was most commonly reported. CONCLUSION: Total costs of minor bleeds from a societal perspective, in AF patients using NOACs, are non trivial and exceed the costs presented in existing literature

Assessment methods in laparoscopic colorectal surgery:a systematic review of available instruments

Background: Laparoscopic surgery has become the golden standard for many procedures, requiring new skills and training methods. The aim of this review is to appraise literature on assessment methods for laparoscopic colorectal procedures and quantify these methods for implementation in surgical training. Materials and methods: PubMed, Embase and Cochrane Central Register of Controlled Trials databases were searched in October 2022 for studies reporting learning and assessment methods for laparoscopic colorectal surgery. Quality was scored using the Downs and Black checklist. Included articles were categorized in procedure-based assessment methods and non-procedure-based assessment methods. A second distinction was made between capability for formative and/or summative assessment. Results: In this systematic review, nineteen studies were included. These studies showed large heterogeneity despite categorization. Median quality score was 15 (range 0–26). Fourteen studies were categorized as procedure-based assessment methods (PBA), and five as non-procedure-based assessment methods. Three studies were applicable for summative assessment. Conclusions: The results show a considerable diversity in assessment methods with varying quality and suitability. To prevent a sprawl of assessment methods, we argue for selection and development of available high-quality assessment methods. A procedure-based structure combined with an objective assessment scale and possibility for summative assessment should be cornerstones.</p

Comorbidities and malignancies negatively affect survival in myelodysplastic syndromes:A population-based study

Population-based studies that contain detailed clinical data on patients with myelodysplastic syndrome (MDS) are scarce. This study focused on the real-world overall survival (OS) of MDS patients in association with comorbidities, specifically malignancies. An observational population-based study using the HemoBase registry was performed, including all patients with MDS diagnosed between 2005 and 2017 in Friesland, a Dutch province. Detailed information about diagnosis, patient characteristics, previous treatment of malignancies, and comorbidities according to the Charlson Comorbidity Index (CCI) was collected from electronic health records. Patients were followed up until June 2019. Kaplan-Meier plots and Cox regression analyses were used to study survival differences. In the 291 patients diagnosed with MDS, the median OS was 25.3 months (95% confidence interval [CI], 20.3-30.2). OS was significantly better for patients with CCI score <4, age <65 years, female sex, and low-risk MDS. Fifty-seven patients (20%) had encountered a prior malignancy (excluding nonmelanoma skin cancer), and a majority (38 patients; 67%) were therapy related. Both therapy-related and secondary MDSs were associated with worse OS (hazard ratio, 1.51; 95% CI, 1.02-2.23 and 1.58; 95% CI, 0.95-2.65, respectively), as compared with de novo MDS patients (P = .04). Patients in remission at time of MDS diagnosis had a similar median OS compared with patients with de novo MDS (25.5 vs 28.3 months). This population-based study involving all newly diagnosed MDS patients over a 13-year period in Friesland showed that multiple comorbidities, including previous malignancies, are associated with shorter OS. OS was not related to the use of radiotherapy or chemotherapy