How I use anticoagulation in atrial fibrillation

Steinberg, Benjamin A.

doi:10.1182/blood-2016-07-693614

Cited by 10 publications

(6 citation statements)

References 68 publications

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“…Instead, there was a notable tendency that patients of EG2b and EG3, the two groups with a high or very high fraction of short-lived patients, were more frequently classified to have FAB type M4 (acute myelomocytic leukemia) or M5 (acute monoblastic leukemia or acute monocytic leukemia) (Table 1 ). The FAB types M4 and M5 have previously been associated with a high mutational burden at diagnosis 36 . This was not confirmed for our cohort, where the median number of mutated genes for patients within EG2b and EG3 was significantly smaller than for patients within EG1 and EG2a (U-Test: P < 0.002; EG2b and EG3: 11; EG1 and EG2a: 17; Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Survival differences and associated molecular signatures of DNMT3A-mutant acute myeloid leukemia patients

Lauber

Correia

Trumpp

et al. 2020

Sci Rep

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Acute myeloid leukemia (AML) is a very heterogeneous and highly malignant blood cancer. Mutations of the DNA methyltransferase DNMT3A are among the most frequent recurrent genetic lesions in AML. The majority of DNMT3A-mutant AML patients shows fast relapse and poor survival, but also patients with long survival or long-term remission have been reported. Underlying molecular signatures and mechanisms that contribute to these survival differences are only poorly understood and have not been studied in detail so far. We applied hierarchical clustering to somatic gene mutation profiles of 51 DNMT3A-mutant patients from The Cancer Genome Atlas (TCGA) AML cohort revealing two robust patient subgroups with profound differences in survival. We further determined molecular signatures that distinguish both subgroups. Our results suggest that FLT3 and/or NPM1 mutations contribute to survival differences of DNMT3A-mutant patients. We observed an upregulation of genes of the p53, VEGF and DNA replication pathway and a downregulation of genes of the PI3K-Akt pathway in short-compared to long-lived patients. We identified that the majority of measured miRNAs was downregulated in the short-lived group and we found differentially expressed microRNAs between both subgroups that have not been reported for AML so far (miR-153-2, miR-3065, miR-95, miR-6718) suggesting that miRNAs could be important for prognosis. In addition, we learned gene regulatory networks to predict potential major regulators and found several genes and miRNAs with known roles in AML pathogenesis, but also interesting novel candidates involved in the regulation of hematopoiesis, cell cycle, cell differentiation, and immunity that may contribute to the observed survival differences of both subgroups and could therefore be important for prognosis. Moreover, the characteristic gene mutation and expression signatures that distinguished short-from long-lived patients were also predictive for independent DNMT3A-mutant AML patients from other cohorts and could also contribute to further improve the European LeukemiaNet (ELN) prognostic scoring system. Our study represents the first in-depth computational approach to identify molecular factors associated with survival differences of DNMT3A-mutant AML patients and could trigger additional studies to develop robust molecular markers for a better stratification of AML patients with DNMT3A mutations. Acute myeloid leukemia (AML) is a highly malignant cancer of myeloid blood cells affecting about one million people globally in 2015 1,2. It most frequently occurs in older adults and shows a relatively poor five-year survival rate of about 25%, which is worsening with increasing age of a patient at diagnosis 3. AML is characterized by a rapid growth of abnormal, immature myeloblasts that lost their ability to differentiate, which replace normal

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Section: Resultsmentioning

confidence: 99%

Survival differences and associated molecular signatures of DNMT3A-mutant acute myeloid leukemia patients

Lauber

Correia

Trumpp

et al. 2020

Sci Rep

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“…NVAF patients were willing to accept higher bleeding risks if a certain threshold in reduced stroke risk could be reached [7], [26]. Steinberg et al considered that involving the patient in the decision making when selecting a DOAC was vital for optimal management in NVAF [27]. Therefore this article encourages physicians to counsel patients about the risks and benefits of treatment and work out which is the best oral anticoagulant agent based on their characteristics (Table 3).…”

Section: Discussionmentioning

confidence: 99%

DOACs vs Vitamin K Antagonists: a Comparison of Phase III Clinical Trials and a Prescriber Support Tool

Pirlog¹,

Pirlog²,

Maghiar³

2019

Open Access Maced J Med Sci

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AIM: The purpose of this article was to systematically review the literature assessing the efficacy and safety of phase III clinical trials for each direct oral anticoagulant versus vitamin K antagonists and to design a ’’go-to’’ table for the prescriber. MATERIAL AND METHODS: A systematic review of specialist literature was conducted to identify RCTs which compared direct oral anticoagulants (DOACs) with standard warfarin treatment. Medline, Em-base, and the Cochrane databases were searched from January 2005- January 2019. The inclusion criteria were randomised controlled trials of oral anticoagulants in patients with non-valvular atrial fibrillation (NVAF). Four publications were phase III randomised control trials (RCTs) included in the final analysis. RESULTS: Regarding the primary outcome in RELY the results were 1.69% per 100-year patients (p/y) for Warfarin compared to 1.11% p/y dabigatran etexilate 150mg BD (twice daily). In ROCKET AF the rates of the primary outcome were 2.2% p/y for warfarin compared to 1.7% p/y for rivaroxaban 20 mg OD (once daily). In ARISTOTLE trial the rates of the primary outcome were 1.60% p/y for warfarin compared to 1.27% p/y for apixaban 5 mg BD. In ENGAGE AF TIMI, the rates of the primary outcome were 1.50% p/y for warfarin compared to 1.18% p/y for edoxaban 60mg BD. CONCLUSION: DOACs showed to be either noninferior or superior to warfarin with regards to the primary outcome with better safety patterns. Our ’’go-to’’ table provides a supportive tool for physicians in preventing medical errors when managing patients on oral anticoagulants.

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“…1 However, multiple challenges making it difficult to determine the optimal dose of warfarin including the long half-life of warfarin, numerous foods that interfere with the actions of warfarin, and drug interactions. 2 To ensure a suitable level of anticoagulation, prothrombin time (PT) standardized by the international normalized ratio (INR) should be monitored closely.…”

Section: Introductionmentioning

confidence: 99%

The Algorithm with Multiple Genotypes on Optimal Warfarin Doses in Korean Patients

Li¹,

Kim²,

Han³

et al. 2020

Clin Exp Thromb Hemost

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How I use anticoagulation in atrial fibrillation

Cited by 10 publications

References 68 publications

Survival differences and associated molecular signatures of DNMT3A-mutant acute myeloid leukemia patients

Survival differences and associated molecular signatures of DNMT3A-mutant acute myeloid leukemia patients

DOACs vs Vitamin K Antagonists: a Comparison of Phase III Clinical Trials and a Prescriber Support Tool

The Algorithm with Multiple Genotypes on Optimal Warfarin Doses in Korean Patients

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