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Journal of Clinical and Experimental... Apr 2014Adequate hemostasis is crucial for the success of invasive dental treatment, since bleeding problems can give rise to complications associated with important... (Review)
Review
INTRODUCTION
Adequate hemostasis is crucial for the success of invasive dental treatment, since bleeding problems can give rise to complications associated with important morbidity-mortality. The dental treatment of patients who tend to an increased risk of bleeding due to the use of anticoagulant and/or antiplatelet drugs raises a challenge in the daily practice of dental professionals. Adequate knowledge of the mechanisms underlying hemostasis, and the optimized management of such patients, are therefore very important issues.
OBJECTIVES
A study is made of the anticoagulant / antiplatelet drugs currently available on the market, with evaluation of the risks and benefits of suspending such drugs prior to invasive dental treatment. In addition, a review is made of the current management protocols used in these patients.
MATERIAL AND METHODS
A literature search was made in the PubMed, Cochrane Library and Scopus databases, covering all studies published in the last 5 years in English and Spanish. Studies conducted in humans and with scientific evidence levels 1 and 2 (metaanalyses, systematic reviews, randomized phase 1 and 2 trials, cohort studies and case-control studies) were considered. The keywords used for the search were: tooth extraction, oral surgery, hemostasis, platelet aggregation inhibitors, antiplatelet drugs, anticoagulants, warfarin, acenocoumarol.
RESULTS AND CONCLUSIONS
Many management protocols have been developed, though in all cases a full clinical history is required, together with complementary hemostatic tests to minimize any risks derived from dental treatment. Many authors consider that patient medication indicated for the treatment of background disease should not be altered or suspended unless so indicated by the prescribing physician. Local hemostatic measures have been shown to suffice for controlling possible bleeding problems resulting from dental treatment. Key words:Tooth extraction, oral surgery, hemostasis, platelet aggregation inhibitors, antiplatelet drugs, anticoagulants, warfarin, acenocoumarol.
PubMed: 24790716
DOI: 10.4317/jced.51215 -
Biomedicine & Pharmacotherapy =... Sep 2023Rivaroxaban is a direct inhibitor of factor Xa, a member of direct oral anticoagulant group of drugs (DOACs). Despite being a widely extended alternative to vitamin K...
Rivaroxaban is a direct inhibitor of factor Xa, a member of direct oral anticoagulant group of drugs (DOACs). Despite being a widely extended alternative to vitamin K antagonists (i.e., acenocoumarol, warfarin) the interindividual variability of DOACs is significant, and may be related to adverse drug reaction occurrence or drug inefficacy, namely hemorrhagic or thromboembolic events. Since there is not a consistent analytic practice to monitor the anticoagulant activity of DOACs, previously reported polymorphisms in genes coding for proteins responsible for the activation, transport, or metabolism of DOACs were studied. The study population comprised 60 healthy volunteers, who completed two randomized, crossover bioequivalence clinical trials between two different rivaroxaban formulations. The effect of food, sex, biogeographical origin and 55 variants (8 phenotypes and 47 single nucleotide polymorphisms) in drug metabolizing enzyme genes (such as CYP2D6, CYP2C9, NAT2) and transporters (namely, ABCB1, ABCG2) on rivaroxaban pharmacokinetics was tested. Individuals dosed under fasting conditions presented lower t (2.21 h vs 2.88 h, β = 1.19, R =0.342, p = 0.012) compared to fed volunteers. NAT2 slow acetylators presented higher AUC corrected by dose/weight (AUC/DW; 8243.90 vs 7698.20 and 7161.25 h*ng*mg /ml*kg, β = 0.154, R =0.250, p = 0.044), higher C/DW (1070.99 vs 834.81 and 803.36 ng*mg /ml*kg, β = 0.245, R =0.320, p = 0.002), and lower t (2.63 vs 3.19 and 4.15 h, β = -0.346, R =0.282, p = 0.047) than NAT2 rapid and intermediate acetylators. No other association was statistically significant. Thus, slow NAT2 appear to have altered rivaroxaban pharmacokinetics, increasing AUC and C. Nonetheless, further research should be conducted to verify NAT2 involvement on rivaroxaban pharmacokinetics and to determine its clinical significance.
Topics: Humans; Rivaroxaban; Healthy Volunteers; Anticoagulants; Polymorphism, Single Nucleotide; Phenotype; Arylamine N-Acetyltransferase
PubMed: 37385211
DOI: 10.1016/j.biopha.2023.115058 -
Hellenic Journal of Cardiology : HJC =... 2021To estimate the incidence of hemorrhagic events in patients with atrial fibrillation (AF) treated with acenocoumarol, and the management cost of those requiring...
BACKGROUND
To estimate the incidence of hemorrhagic events in patients with atrial fibrillation (AF) treated with acenocoumarol, and the management cost of those requiring hospitalization in Greece.
METHODS
A nationwide telephone survey was conducted between December 2017 and January 2018, to identify cardiologists who treat AF patients with acenocoumarol. A total of 300 cardiologists were selected and reported the number of AF acenocoumarol-treated patients during the past 12 months and the number of those who experienced a hemorrhagic event. The hospital charges to sickness fund and the cost of resource utilization of AF patients hospitalized between January 2013 and June 2017 at a tertiary hospital in Athens due to acenocoumarol-related bleedings were retrieved.
RESULTS
Out of 48,255 AF patients, 12,633 (26.2%) were treated with acenocoumarol. In all, 5.1% of patients experienced a hemorrhagic event with the incidence of bleeding requiring hospitalization being 1.7%. The most common bleeding site was the gastrointestinal system (51.5%). The mean (95% CI) management cost per bleeding event requiring hospitalization was €1,202 (€1,058-€1,420). The higher cost was that of intracranial bleeding €3,887 (€2,700-€5,046). The expected annual economic burden for the management of bleedings related to acenocoumarol and requiring hospitalization was estimated at €1,463,955.
CONCLUSIONS
The incidence of bleeding events in AF acenocoumarol-treated patients in Greece as well as the estimated annual economic burden for the management of bleeding events requiring hospitalization, emphasize the need to comply with the current guidelines and to optimize therapeutic strategies for the management of AF side effects with oral anticoagulants, particularly in patients with high bleeding risk.
Topics: Acenocoumarol; Anticoagulants; Atrial Fibrillation; Greece; Hospitalization; Humans; Incidence; Retrospective Studies; Stroke
PubMed: 32683128
DOI: 10.1016/j.hjc.2020.06.013 -
Cureus Mar 2023Coronavirus disease 2019 (COVID-19) causes endothelial damage, blood stasis, and an overall state of hypercoagulability. This makes COVID a huge risk factor for venous... (Review)
Review
Coronavirus disease 2019 (COVID-19) causes endothelial damage, blood stasis, and an overall state of hypercoagulability. This makes COVID a huge risk factor for venous thromboembolism (VTE) and arterial thromboembolism (ATE). Twenty percent of COVID-19 patients suffer from coagulation abnormalities like pulmonary embolism, myocardial infarction, stroke, deep vein thrombosis, etc. Ovarian vein thrombosis (OVT) has been previously linked to post-partum period, pregnancy, hypercoagulable state, or malignancy. We analyzed PubMed and Google Scholar databases for research and publications regarding OVT in patients with COVID-19. The search yielded nine case reports. These case reports were found to implicate COVID-associated coagulopathy (CAC) as an additional risk factor for ovarian vein thrombosis (OVT). OVT most commonly presents with abdominal pain and fever, making it difficult to diagnose, owing to the similarity in presentation with multiple other pathologies. OVT can be diagnosed radiologically with ultrasound, magnetic resonance imaging (MRI) scan, or CT scan with IV contrast. CT has been used as the modality of choice for diagnosing OVT. Although rare, OVT can cause life-endangering complications by extension of thrombus into systemic veins or pulmonary artery embolization. Therefore, early diagnosis and treatment are vital. There is no official guideline for the treatment of OVT post-COVID. However, the literature supports the use of apixaban or enoxaparin/acenocoumarol.
PubMed: 37090373
DOI: 10.7759/cureus.36437 -
Journal of Comparative Effectiveness... Aug 2023Healthcare resources usage and costs associated to nonvalvular atrial fibrillation (NVAF) were analyzed in Spain. This is an observational and retrospective study on... (Observational Study)
Observational Study
Healthcare resources usage and costs associated to nonvalvular atrial fibrillation (NVAF) were analyzed in Spain. This is an observational and retrospective study on patients with NVAF who started their treatment with apixaban or acenocoumarol between 1 January 2015 and 31 December 2017. 2160 patients treated with apixaban were paired (1:1) with patients treated with acenocoumarol (propensity score matching). Apixaban reduced the incidence of strokes and systemic embolisms, minor and major bleedings and deaths, versus acenocoumarol. Apixaban led to reductions of 80, 55 and 43% in costs related to nursing visits, hospitalizations, and emergency visits, respectively, leading to annual cost savings of €274/patient, from the perspective of society. Our results suggested that apixaban is a cost-effective alternative for patients with NVAF.
Topics: Humans; Acenocoumarol; Atrial Fibrillation; Anticoagulants; Spain; Retrospective Studies; Pyridones; Stroke; Delivery of Health Care; Rivaroxaban
PubMed: 37489950
DOI: 10.57264/cer-2023-0007 -
Digestive and Liver Disease : Official... Aug 2015Acute gastrointestinal bleeding represents the most common adverse event associated with the use of oral anticoagulant therapy. Due to increasing prescription of... (Review)
Review
Acute gastrointestinal bleeding represents the most common adverse event associated with the use of oral anticoagulant therapy. Due to increasing prescription of anticoagulants worldwide, gastroenterologists are more and more called to deal with bleeding patients taking these medications. Their management is challenging because several issues have to be taken into account, such as the severity of bleeding, the intensity of anticoagulation, the patient's thrombotic risk and endoscopy findings. The recent introduction into the marketplace of new direct oral anticoagulants, for whom specific reversal agents are still lacking, further contributes to make the decision-making process even more demanding. Available evidence on this topic is limited and practice guidelines by gastroenterology societies only marginally address key issues for clinicians, including when and how to reverse coagulopathy, the optimal timing of endoscopy and when and how to resume anticoagulation thereafter. The present paper reviews the evidence in the literature and provides practical algorithms to support clinicians in the management of patients on anticoagulants who present with acute gastrointestinal bleeding.
Topics: Acenocoumarol; Acute Disease; Algorithms; Anticoagulants; Coagulants; Dabigatran; Endoscopy, Gastrointestinal; Gastrointestinal Hemorrhage; Humans; Rivaroxaban; Vitamin K; Warfarin
PubMed: 25935464
DOI: 10.1016/j.dld.2015.03.029 -
British Journal of Clinical Pharmacology Feb 2021Acenocoumarol is a vitamin-K antagonist (VKA) primarily used in certain countries (e.g. India, Netherlands, Spain). The half-life of acenocoumarol is similar to that of...
Clinical outcomes of nonvitamin K oral anticoagulants and acenocoumarol for stroke prevention in contemporary practice: A population-based propensity-weighted cohort study.
AIMS
Acenocoumarol is a vitamin-K antagonist (VKA) primarily used in certain countries (e.g. India, Netherlands, Spain). The half-life of acenocoumarol is similar to that of non-VKA oral anticoagulants (NOAC), unlike warfarin, and this could affect comparative effectiveness and safety (CES). However, data on CES for NOAC come almost exclusively from studies using warfarin as the comparator. We aimed to assess outcomes of NOAC and acenocoumarol in people with non-valvular atrial fibrillation (NVAF) in real-world clinical practice.
METHODS
This is a population-based retrospective cohort study. All new users of oral anticoagulants from November 2011 to December 2015 with NVAF were included (n = 41,560). Data were obtained by linking several health electronic records of the Valencia region, Spain. Incidence rates were estimated. We used the inverse probability of treatment weighted Cox analysis to control for indication bias when assessing the risk of effectiveness and safety outcomes for each NOAC compared with acenocoumarol. Several sensitivity analyses were performed.
RESULTS
We did not find differences in the risk of mortality, ischaemic stroke or any gastrointestinal bleeding. However, we did find a decreased risk of intracranial haemorrhage for dabigatran (HR: 0.34, 95% CI 0.20-0.56) and rivaroxaban (HR: 0.55, 95% CI 0.35-0.85) as compared to acenocoumarol. In subanalyses, apixaban showed a higher risk of ischaemic stroke in high-risk persons (≥75 years and CHA2DS2-VASC score ≥ 2).
CONCLUSIONS
No differences in clinical outcomes were found between NOAC and acenocoumarol overall, although dabigatran and rivaroxaban showed a lower risk of intracranial haemorrhage. Findings on the potential inferiority of specific NOAC in high-risk subgroups should be studied further.
Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cohort Studies; Dabigatran; Humans; India; Netherlands; Retrospective Studies; Rivaroxaban; Spain; Stroke
PubMed: 32530052
DOI: 10.1111/bcp.14430 -
Drug Discoveries & Therapeutics 2018We investigated the impact of non-genetics factors, and single nucleotide polymorphisms (SNPs) in VKORC1, CYP2C9, CYP4F2, and GGCX on acenocoumarol dosage in Moroccan...
Effect of CYP2C9, VKORC1, CYP4F2, and GGCX gene variants and patient characteristics on acenocoumarol maintenance dose: Proposal for a dosing algorithm for Moroccan patients.
We investigated the impact of non-genetics factors, and single nucleotide polymorphisms (SNPs) in VKORC1, CYP2C9, CYP4F2, and GGCX on acenocoumarol dosage in Moroccan adult's patients, in order to develop an algorithm to predict acenocoumarol dose for Moroccan patients. Our study consisted of 217 Moroccan patients taking a maintenance dose of acenocoumarol for various indications. The patients were genotyped for VKORC1 -1639 G>A, VKORC1 1173 C>T, CYP2C9*2, CYP2C9*3, CYP4F2 1347 G>A and GGCX 12970 C>G SNPs. The statistical analysis was performed using the SPSS software. The age and SNPs in VKORC1 and CYP2C9 were significantly associated with the weekly acenocoumarol dose requirement (p = 0.023, p = 0.0001 and p = 0.001 respectively). There was no association found between the weekly acenocoumarol dose and the CYP4F2 or GGCX variants (p-value > 0.05). Non-parametric analysis confirmed the accumulate effect of variant alleles at VKORC1 -1639 G>A, VKORC1 1173 C>T and CYP2C9 SNPs on the acenocoumarol dose requirement. With 90.24% less dose required for one patient carrying homozygote variant at VKORC1 -1173 (TT) and CYP2C9 *x/*x haplotype. The multiple linear regression analysis showed that mutation in VKORC1 -1639, VKORC1 1173 SNPs, or in CYP2C9 haplotype reduces the mean acenocoumarol weekly dose to 25.4%, 23.4% and 6.2%, respectively. The R2 for multiple regression analysis final model was found to be 35.9%. In this work we were able to establish the factors influencing interindividual sensitivity to the anticoagulant therapy that can help physicians to predict optimal dose requirement for long term therapy.
Topics: Acenocoumarol; Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Carbon-Carbon Ligases; Cytochrome P-450 CYP2C9; Cytochrome P450 Family 4; Drug Dosage Calculations; Female; Humans; Linear Models; Maintenance Chemotherapy; Male; Middle Aged; Morocco; Pharmacogenomic Variants; Polymorphism, Single Nucleotide; Vitamin K Epoxide Reductases; Young Adult
PubMed: 29760340
DOI: 10.5582/ddt.2017.01063 -
The New England Journal of Medicine Nov 1992In most countries, heparin is used in the initial treatment of patients with deep-vein thrombosis. Well-designed studies establishing the efficacy of heparin therapy are... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
In most countries, heparin is used in the initial treatment of patients with deep-vein thrombosis. Well-designed studies establishing the efficacy of heparin therapy are lacking, however. Treatment with acenocoumarol alone, according to the hypothesis that high dosages of oral anticoagulants obviate the need for heparin, is considered an effective alternative in some countries.
METHODS
In a randomized, double-blind study we compared the efficacy and safety of continuous intravenous heparin plus acenocoumarol with the efficacy and safety of acenocoumarol alone in the initial treatment of outpatients with proximal-vein thrombosis. The principal study end point was a confirmed symptomatic extension or recurrence of venous thromboembolism during six months of follow-up. In addition, we assessed asymptomatic extension or pulmonary embolism by repeating venography and lung scanning after the first week of treatment. The incidence of major bleeding was determined during three months of follow-up.
RESULTS
The study was terminated early by the Data Safety and Monitoring Committee because of an excess of symptomatic events in the group that received acenocoumarol alone (in 12 of 60 patients [20 percent], as compared with 4 of 60 patients [6.7 percent] in the combined-therapy group by intention-to-treat analysis; P = 0.058). Asymptomatic extension of venous thrombosis was observed in 39.6 percent of the patients in the acenocoumarol group and in 8.2 percent of patients treated with heparin plus acenocoumarol (P < 0.001). Major bleeding complications were infrequent and comparable in the two groups.
CONCLUSIONS
Patients with proximal-vein thrombosis require initial treatment with full-dose heparin, which can safely be combined with acenocoumarol therapy.
Topics: Acenocoumarol; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Hemorrhage; Heparin; Humans; Male; Middle Aged; Pulmonary Embolism; Recurrence; Thrombophlebitis
PubMed: 1406880
DOI: 10.1056/NEJM199211193272103 -
Clinical Cardiology Oct 2017Thromboembolic complications can be life-threatening during atrial fibrillation (AF) catheter ablation. The aim of our study was to evaluate the safety and efficacy of... (Comparative Study)
Comparative Study
BACKGROUND
Thromboembolic complications can be life-threatening during atrial fibrillation (AF) catheter ablation. The aim of our study was to evaluate the safety and efficacy of continuous treatment using direct oral anticoagulants (DOACs) as an alternative to uninterrupted acenocoumarol for periprocedural anticoagulation.
HYPOTHESIS
Continuous treatment with DOACs has similar safety and efficacy compared to acenocoumarol.
METHODS
We enrolled 474 patients (mean age, 58 years; 68.4% male) undergoing AF catheter ablation between June 2013 and December 2016. All patients were equally assigned to take acenocoumarol (group 1, 136 patients) or DOACs (group 2, 338 patients) for ≥2 months before the procedure. We compared thromboembolic and bleeding complications between the 2 groups.
RESULTS
Our analysis showed no significant difference in major and minor complications between the 2 patient groups. Specifically, 3 of 136 patients (2.2%) using uninterrupted acenocoumarol had a major complication (1 patient [0.7%] had transient ischemic attack resolved 8 hours later, 1 [0.7%] had pericardial tamponade, and 1 [0.7%] had a subcapsular renal hematoma) and 2 patients (1.4%) had minor complications (1 [0.7%] pseudoaneurysm and 1 [0.7%] groin hematoma). In group 2, 1 of 338 patients (0.3%) had a major complication (transient ischemic attack). In the same group, 7 patients (2.1%) had a minor complication (1 patient [0.3%] presented with pseudoaneurysm, 4 [1.2%] with pericardial effusion <1 cm, 1 [0.3%] femoral arteriovenous fistula between the femoral artery and femoral vein, and 1 [0.7%] groin hematoma).
CONCLUSIONS
DOACs and acenocoumarol have similar safety and effectiveness regarding thromboembolic complications prevention without increasing bleeding complications.
Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Catheter Ablation; Dabigatran; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Prospective Studies; Pyrazoles; Pyridones; Registries; Risk Factors; Rivaroxaban; Thromboembolism; Time Factors; Treatment Outcome
PubMed: 28561951
DOI: 10.1002/clc.22734