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1.
J Physiol Pharmacol ; 74(4)2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37865961

RESUMO

Acute pancreatitis (AP) is the most common gastrointestinal disease leading to hospitalizations and unexpected deaths. The development of AP leads to damage of the pancreatic microcirculation with a cascade of subsequent events resulting, among others, in coagulopathy. Previous research showed that anticoagulants can be important therapeutic agents. Heparin and acenocoumarol can alleviate the course of AP, as well as accelerate healing and post-inflammatory regeneration of the pancreas. The aim of this study was to determine whether warfarin, a drug with more stable effects than acenocoumarol, affects the healing and regeneration of the pancreas in the cerulein-induced AP. AP was evoked in Wistar male rats by intraperitoneal administration of cerulein. The first dose of warfarin (45, 90 or 180 µg/kg) was administered 24 hours after the first dose of cerulein and the doses of warfarin were repeated once a day in subsequent 10 days. The severity of AP was assessed immediately after the last dose of cerulein, as well as at days 1, 2, 3, 5, and 10 after AP induction. Treatment with warfarin dose-dependently increased international normalized ratio (INR) and attenuated the severity of pancreatitis in histological examination and accelerated pancreatic recovery. These effects were accompanied with a faster reduction in the AP-evoked increase in serum activity of amylase and lipase, the serum concentration of pro-inflammatory interleukin-1ß, and the plasma level of D-Dimer. In addition, treatment with warfarin decreased pancreatic weight (an index of pancreatic edema) and improved pancreatic blood flow in rats with AP. The therapeutic effect was particularly pronounced after the administration of warfarin at a dose of 90 µg/kg. We conclude that treatment with warfarin accelerated regeneration of the pancreas and recovery in the course of cerulein-induced mild-edematous acute pancreatitis.


Assuntos
Pancreatite , Ratos , Masculino , Animais , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Pancreatite/patologia , Varfarina/farmacologia , Varfarina/uso terapêutico , Ceruletídeo/toxicidade , Ratos Wistar , Acenocumarol/uso terapêutico , Doença Aguda , Pâncreas/patologia
2.
J Comp Eff Res ; 12(8): e230007, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37489950

RESUMO

Aim: Healthcare resources usage and costs associated to nonvalvular atrial fibrillation (NVAF) were analyzed in Spain. Methods: 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. Results: 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. Conclusion: Our results suggested that apixaban is a cost-effective alternative for patients with NVAF.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Acenocumarol/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Anticoagulantes/uso terapêutico , Espanha/epidemiologia , Estudos Retrospectivos , Piridonas/uso terapêutico , Atenção à Saúde , Rivaroxabana
3.
Artigo em Inglês | MEDLINE | ID: mdl-35843922

RESUMO

Background: Genetic factors play an important role in deep vein thrombosis (DVT). The duration of anticoagulation therapy in patients with verified genetic inheritance and previous events of DVT is still questionable. Case reports: We present three cases of siblings (two brothers and one sister) with verified Venous thromboembolism (VTE) and genetic inheritance. The first case is a 33 y.o. male who was admitted with bilateral massive pulmonary thromboembolism and DVT of the right femoral vein. He had an episode of DVT 4 years ago. Fibrinolytic therapy was introduced immediately. Afterwards, unfractionated heparin was introduced, and then switched to enoxaparin and acenocoumarol. Because of inappropriate INR, it was switched then to rivaroxaban. The imaging methods showed significant improvement, and the patient was discharged from the hospital with rivaroxaban at 2x15 mg/day for another 2 weeks and was instructed to continue 20 mg/day until his next control. In the meantime, the second case, a 36 y.o. male, brother to the first patient, came with vein thrombosis of vena saphena magna of the left leg. Treatment with Acenocoumarol was started and continued for 2 years until complete resolution of the thrombi, and then it was changed to Aspirin. The third case is the sister of the first 2 cases, a 38 y.o female with symptoms and findings almost similar to those in the second case. She was treated with Acenocoumarol for 6 months. Doppler ultrasound showed complete resolution of the thrombosis and anticoagulation therapy was stopped. Genetic investigations for mutation showed presence of homozygous gene mutation for Prothrombin (PTB G20210A) in the first patient, his brother (the second case) was compound heterozygote for PTB and for MTHFR C677T, and his sister (third case) was heterozygous only for the PTB mutation. According to the clinical (recurrent unprovoked DVT with thromboembolic complications) and genetic testing (homozygous gene mutation for PTB) in the first patient, we decided to continue the secondary thromboprophylaxis with rivaroxaban 10 mg/day indefinitely. Conclusion: Testing for genetically inherited thrombophilia should be included in the risk assessment for recurrence, and performed in all patients under 50 y.o. who have a first, non-provoked episode of thrombosis, in order to determine the duration of anticoagulation therapy.


Assuntos
Trombofilia , Trombose , Tromboembolia Venosa , Trombose Venosa , Acenocumarol/uso terapêutico , Anticoagulantes/uso terapêutico , Feminino , Heparina/uso terapêutico , Humanos , Masculino , Rivaroxabana/efeitos adversos , Trombofilia/complicações , Trombofilia/tratamento farmacológico , Trombofilia/genética , Trombose/induzido quimicamente , Trombose/complicações , Trombose/tratamento farmacológico , Trombose Venosa/tratamento farmacológico , Trombose Venosa/genética
4.
J Int Med Res ; 50(6): 3000605221103959, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35748017

RESUMO

Effective prevention of thromboembolism is essential for patients with mechanical prosthetic heart valves. For this group of patients, vitamin K antagonists (VKAs) remain the drug group of choice despite the widespread use of new anticoagulants in other diseases. As a consequence, warfarin resistance remains a serious challenge for physicians. The current report describes a 65-year-old male patient that had a mechanical prosthetic aortic valve implanted due to severe aortic insufficiency after infective endocarditis. Despite consistent increases in his warfarin dose, the level of international normalized ratio (INR) remained very low. The patient was considered to have warfarin resistance. Warfarin was successfully replaced by another VKA, acenocoumarol, which resulted in a stable INR observed over 1 year of follow-up. Achieving the target INR in patients with mechanical prosthetic heart valves using VKAs is the main goal of thromboprophylaxis. Although the genetic changes that cause warfarin resistance are understood, the options to overcome these pharmacogenetic issues remain limited. Based on the success with this current patient, physicians with similar patients with warfarin resistance might wish to consider replacing warfarin with acenocoumarol.


Assuntos
Próteses Valvulares Cardíacas , Tromboembolia Venosa , Acenocumarol/uso terapêutico , Idoso , Anticoagulantes/uso terapêutico , Fibrinolíticos/uso terapêutico , Próteses Valvulares Cardíacas/efeitos adversos , Humanos , Coeficiente Internacional Normatizado , Masculino , Erros Inatos do Metabolismo , Tromboembolia Venosa/tratamento farmacológico , Varfarina/uso terapêutico
5.
Ned Tijdschr Geneeskd ; 1652021 09 09.
Artigo em Holandês | MEDLINE | ID: mdl-34523845

RESUMO

Acenocoumarol and phenprocoumon are vitamin K antagonists (VKA) with average half-lives of 11 hours and 160 hours, respectively. They are used to treat and prevent thrombosis in mechanical cardiac valve replacement, atrial fibrillation and venous thromboembolism. There are historical regional differences in preferred VKA in the Netherlands. Safe and effective treatment requires the international normalized ratios (INRs) to be in the therapeutic range, and stable. Theoretically, the longer-acting phenprocoumon would yield a higher time in therapeutic range (TTR) and lower INR variability. In practice, switching from acenocoumarol to phenprocoumon eventually improves INR variability and in some patients TTR as well. However, during the preceding transition period, INRs are more often volatile and supratherapeutic. Furthermore, switching to an alternative VKA could weaken integrated care, as other healthcare providers are less experienced with it. Healthcare providers must coordinate an intended switch with the anticoagulation clinic.


Assuntos
Acenocumarol , Femprocumona , Acenocumarol/uso terapêutico , Anticoagulantes , Coagulação Sanguínea , Humanos , Coeficiente Internacional Normatizado , Femprocumona/farmacologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-34073370

RESUMO

Introduction: The use of vitamin K antagonists (VKAs) in non-valvular atrial fibrillation (NVAF) is complicated due to the narrow therapeutic margin they present and their unpredictable dose-response relationship. Most studies are based on warfarin, with the results being extrapolated to acenocoumarol. However, studies comparing the two treatments in terms of the degree of anticoagulation control are scarce, justifying the present study. Main factors associated with poor control of time in therapeutic range (TTR) of anticoagulated patients are also studied. Methods: Cross-sectional study, with real-world data from patients treated in primary care (PC). Data were obtained from the System for the Improvement of Research in PC (SIDIAP) database, covering 60,978 NVAF-anticoagulated patients from 287 PC centres in 2018. Descriptive statistics were derived, and odds ratios were estimated by multivariate logistic regression. Results: 41,430 patients were considered: 93% were being treated with acenocoumarol and 7% with warfarin. There was no difference in poor control of TTR between the two types of VKA treatment, acenocoumarol and warfarin (38.9 vs. 38.4; p = 0.610). Poor anticoagulation control was mainly associated with advanced alcoholism (OR = 1.38), liver failure (OR = 1.37) and intracranial haemorrhage (OR = 1.35) as well as female sex, age < 60 years, cardiovascular history, diabetes mellitus and other variables. Conclusions: There is no association between poor anticoagulation control and the type of VKA treatment administered. Factors associated with poor control of TTR must be considered in clinical practice to improve control and decision-making.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Acenocumarol/uso terapêutico , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Atenção Primária à Saúde , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Varfarina/uso terapêutico
7.
Molecules ; 26(5)2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800767

RESUMO

Vitamin K antagonists are indicated for the thromboprophylaxis in patients with mechanical prosthetic heart valves (MPHV). However, it is unclear whether some differences between acenocoumarol and warfarin in terms of anticoagulation quality do exist. We included 2111 MPHV patients included in the nationwide PLECTRUM registry. We evaluated anticoagulation quality by the time in therapeutic range (TiTR). Factors associated with acenocoumarol use and with low TiTR were investigated by multivariable logistic regression analysis. Mean age was 56.8 ± 12.3 years; 44.6% of patients were women and 395 patients were on acenocoumarol. A multivariable logistic regression analysis showed that patients on acenocoumarol had more comorbidities (i.e., ≥3, odds ratio (OR) 1.443, 95% confidence interval (CI) 1.081-1.927, p = 0.013). The mean TiTR was lower in the acenocoumarol than in the warfarin group (56.1 ± 19.2% vs. 61.6 ± 19.4%, p < 0.001). A higher prevalence of TiTR (<60%, <65%, or <70%) was found in acenocoumarol users than in warfarin ones (p < 0.001 for all comparisons). Acenocoumarol use was associated with low TiTR regardless of the cutoff used at multivariable analysis. A lower TiTR on acenocoumarol was found in all subgroups of patients analyzed according to sex, hypertension, diabetes, age, valve site, atrial fibrillation, and INR range. In conclusion, anticoagulation quality was consistently lower in MPHV patients on acenocoumarol compared to those on warfarin.


Assuntos
Acenocumarol/uso terapêutico , Anticoagulantes/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Doenças das Valvas Cardíacas/terapia , Próteses Valvulares Cardíacas/efeitos adversos , Tromboembolia Venosa/tratamento farmacológico , Varfarina/uso terapêutico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tromboembolia Venosa/etiologia
8.
Lancet Neurol ; 20(5): 341-350, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33765420

RESUMO

BACKGROUND: Cervical artery dissection is a major cause of stroke in young people (aged <50 years). Historically, clinicians have preferred using oral anticoagulation with vitamin K antagonists for patients with cervical artery dissection, although some current guidelines-based on available evidence from mostly observational studies-suggest using aspirin. If proven to be non-inferior to vitamin K antagonists, aspirin might be preferable, due to its ease of use and lower cost. We aimed to test the non-inferiority of aspirin to vitamin K antagonists in patients with cervical artery dissection. METHODS: We did a multicentre, randomised, open-label, non-inferiority trial in ten stroke centres across Switzerland, Germany, and Denmark. We randomly assigned (1:1) patients aged older than 18 years who had symptomatic, MRI-verified, cervical artery dissection within 2 weeks before enrolment, to receive either aspirin 300 mg once daily or a vitamin K antagonist (phenprocoumon, acenocoumarol, or warfarin; target international normalised ratio [INR] 2·0-3·0) for 90 days. Randomisation was computer-generated using an interactive web response system, with stratification according to participating site. Independent imaging core laboratory adjudicators were masked to treatment allocation, but investigators, patients, and clinical event adjudicators were aware of treatment allocation. The primary endpoint was a composite of clinical outcomes (stroke, major haemorrhage, or death) and MRI outcomes (new ischaemic or haemorrhagic brain lesions) in the per-protocol population, assessed at 14 days (clinical and MRI outcomes) and 90 days (clinical outcomes only) after commencing treatment. Non-inferiority of aspirin would be shown if the upper limit of the two-sided 95% CI of the absolute risk difference between groups was less than 12% (non-inferiority margin). This trial is registered with ClinicalTrials.gov, NCT02046460. FINDINGS: Between Sept 11, 2013, and Dec 21, 2018, we enrolled 194 patients; 100 (52%) were assigned to the aspirin group and 94 (48%) were assigned to the vitamin K antagonist group. The per-protocol population included 173 patients; 91 (53%) in the aspirin group and 82 (47%) in the vitamin K antagonist group. The primary endpoint occurred in 21 (23%) of 91 patients in the aspirin group and in 12 (15%) of 82 patients in the vitamin K antagonist group (absolute difference 8% [95% CI -4 to 21], non-inferiority p=0·55). Thus, non-inferiority of aspirin was not shown. Seven patients (8%) in the aspirin group and none in the vitamin K antagonist group had ischaemic strokes. One patient (1%) in the vitamin K antagonist group and none in the aspirin group had major extracranial haemorrhage. There were no deaths. Subclinical MRI outcomes were recorded in 14 patients (15%) in the aspirin group and in 11 patients (13%) in the vitamin K antagonist group. There were 19 adverse events in the aspirin group, and 26 in the vitamin K antagonist group. INTERPRETATION: Our findings did not show that aspirin was non-inferior to vitamin K antagonists in the treatment of cervical artery dissection. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Stroke Funds Basel, University Hospital Basel, University of Basel, Academic Society Basel.


Assuntos
Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Dissecação da Artéria Carótida Interna/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Dissecação da Artéria Vertebral/tratamento farmacológico , Acenocumarol/uso terapêutico , Adulto , Dissecação da Artéria Carótida Interna/complicações , Dissecação da Artéria Carótida Interna/diagnóstico por imagem , Dinamarca , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Femprocumona/uso terapêutico , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Suíça , Dissecação da Artéria Vertebral/complicações , Dissecação da Artéria Vertebral/diagnóstico por imagem , Varfarina/uso terapêutico
9.
Eur J Clin Invest ; 51(1): e13356, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33180323

RESUMO

BACKGROUND: Splanchnic vein thrombosis (SVT) is an uncommon but potentially life-threatening disease usually related to different underlying clinical conditions. The risk of SVT recurrences is high over time in patients with an underlying permanent prothrombotic condition. Vitamin K antagonists (VKA) represent the mainstay of treatment for SVT. Data about the efficacy and safety of direct oral anticoagulants (DOACs) are reported in the literature for the treatment of acute SVT, but less is known about their application for the secondary prophylaxis of venous thromboembolism (VTE). The aim of this study was to assess the efficacy and safety of long-term DOACs therapy in patients at high-risk of thrombosis, compared to VKA. METHODS: This is a retrospective single-centre study including 70 patients with SVT on long-term anticoagulant treatment with VKA followed-up at our Units between January 2017 and December 2019. All the patients were at high thrombotic risk defined as the presence of a permanent prothrombotic condition requiring long-term anticoagulation. During follow-up, 28 patients were shifted to DOACs and their clinical outcomes were compared to those of the patients who continued VKA therapy. All the arterial and venous thrombotic events of the splanchnic and extra-splanchnic districts as well as the haemorrhagic adverse events occurring during follow-up were recorded. RESULTS: Of the seventy patients enrolled in the study, 36 patients (51.4%) had a single-segment involvement thrombosis (28.5% of portal vein, 7.1% of superior mesenteric vein, 4.3% of splenic vein, 11.5% of hepatic veins) and 34 patients (48.6%) had multi-segment involvement at the time of diagnosis. 42 patients (60%) continued VKA therapy and 28 (40%) were switched to DOACs. Median follow-up was 6 years (range 2-8) during VKA and 1.9 years (range 1-5.2) during DOACs. The incidence of thrombotic events was similar between patients on VKA and those on DOACs. Patients on VKA developed deep vein thrombosis (DVT), and of the patients on DOACs 1 developed NSTEMI and 1 DVT. No major haemorrhagic events occurred. Minor bleedings occurred in 26% of patients on VKA and in none of the DOACs patients (P: 0.09). CONCLUSIONS: Our results highlight that DOACs could represent an effective and safe alternative to the VKA for secondary prophylaxis in SVT patients at high risk of thrombosis.


Assuntos
Inibidores do Fator Xa/uso terapêutico , Hemorragia/induzido quimicamente , Isquemia Mesentérica/tratamento farmacológico , Veia Porta , Trombose Venosa/tratamento farmacológico , Acenocumarol/uso terapêutico , Adulto , Anticoagulantes/uso terapêutico , Síndrome de Budd-Chiari/tratamento farmacológico , Duração da Terapia , Feminino , Hemorragia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Prevenção Secundária , Tiazóis/uso terapêutico , Varfarina/uso terapêutico
10.
An Sist Sanit Navar ; 43(2): 251-254, 2020 Aug 31.
Artigo em Espanhol | MEDLINE | ID: mdl-32865189

RESUMO

Infection caused by SARS-CoV-2 (COVID-19) is associated with an increased risk of thromboembolic disease. So-me authors recommend anticoagulation at therapeutic doses for, at least, the most severely ill patients; this practice is not free of risks, which is why only thromboembolic prophylaxis is recommended by other consensuses. In the case of previously anticoagulated patients, changing the oral anticoagulant for a low molecular weight heparin (LMWH) is generally recommended. We present the cases of two patients admitted due to COVID-19, without serious clinical data, in whom anticoagulation (acenocoumarol and rivaroxaban, respectively) was replaced by LMWH at therapeutic doses, both presenting abdominal bleeding. This type of bleeding is an infrequent complication in anticoagulated patients, but the concurrence of two cases in a short period of time in the context of the COVID-19 pandemic leads us to consider that there is not yet any clear evidence on therapeutic anticoagulation in SARS-CoV-2 infection.


Assuntos
Anticoagulantes/efeitos adversos , Betacoronavirus , Infecções por Coronavirus/complicações , Hematoma/induzido quimicamente , Pneumonia Viral/complicações , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/virologia , Abdome , Acenocumarol/efeitos adversos , Acenocumarol/uso terapêutico , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , COVID-19 , Feminino , Hematoma/diagnóstico , Heparina de Baixo Peso Molecular/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Pandemias , Rivaroxabana/efeitos adversos , Rivaroxabana/uso terapêutico , SARS-CoV-2 , Tromboembolia Venosa/tratamento farmacológico
11.
Medicine (Baltimore) ; 99(36): e22054, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899067

RESUMO

BACKGROUND: Anticoagulant therapy is used for stroke prevention and proved to be effective and safe in the long term. The study aims to analyse the cost-effectiveness relationship of using of direct-acting oral anticoagulants vs vitamin K antagonists to prevent ischaemic stroke in patients with nonvalvular atrial fibrillation, including all the active ingredients marketed in Spain, prescribed for 2 years in the Primary Care service of the Institut Català de la Salut. METHODS: Population-based cohort study, in which the cost of the 2 treatment groups will be evaluated. Direct costs (pharmacy, primary care, emergency and hospitalization) and indirect costs (lost productivity) will be included from a social perspective. Effectiveness (assessed as the occurrence of a health event, the 1 of primary interest being stroke) will be determined, with a 2-year time horizon and a 3% discount rate. The average cost of the 2 groups of drugs will be compared using a regression model to determine the factors with the greatest influence on determining costs. We will carry out a univariate ('one-way') deterministic sensitivity analysis. DISCUSSION: We hope to provide relevant information about direct and indirect costs of oral anticoagulants, which, together with aspects of effectiveness and safety, could help shape the consensual decision-making of evaluating bodies.


Assuntos
Acenocumarol/economia , Anticoagulantes/economia , Fibrilação Atrial/tratamento farmacológico , Isquemia Encefálica/patologia , Ensaios Clínicos Pragmáticos como Assunto/métodos , Varfarina/economia , Acenocumarol/administração & dosagem , Acenocumarol/uso terapêutico , Administração Oral , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Isquemia Encefálica/prevenção & controle , Análise Custo-Benefício , Inibidores do Fator Xa , Humanos , Atenção Primária à Saúde/organização & administração , Segurança , Espanha/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento , Vitamina K/antagonistas & inibidores , Varfarina/administração & dosagem , Varfarina/uso terapêutico
12.
PLoS One ; 15(7): e0235639, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32649714

RESUMO

BACKGROUND: Treatment with vitamin K antagonists (VKA) requires a high proportion of time in the therapeutic range (TTR) and a low international normalised ratio (INR) variability to be maximally safe and effective. Switching from short-acting acenocoumarol to long-acting phenprocoumon could improve VKA control. AIMS: We assessed whether switching from acenocoumarol to phenprocoumon improves the time in the therapeutic range (TTR) and INR variability. METHODS AND RESULTS: In a retrospective cohort with data on 236,957 patients-years of VKA management from two first-line anticoagulation clinics in the Netherlands, we identified 124 patients in target range 2-3, 269 patients in target range 2-3.5 and 98 patients in target range 2.5-3.5 who switched from acenocoumarol to phenprocoumon. They were matched in a 1:2 ratio to non-switching controls using propensity score matching. Over the first 180 days after a switch, switchers' TTR declined 5 (95% CI 1 to 10), 10 (95% CI 7 to 13) and 5 (95% CI 0 to 11) percentage points relative to non-switchers, in target ranges 2-3, 2-3.5 and 2.5-3.5. Anticoagulation was more often supra-therapeutic in switchers, and switchers had a higher INR variability. In the following 180 days, TTR in switchers became 1 (95% CI -4 to 6), 4 (95% CI 0 to 7) and 6 (95% CI 1 to 12) percentage points better than in non-switchers. Switchers' INRs were much more stable than non-switchers'. CONCLUSION: Eventually, a switch from acenocoumarol to phenprocoumon leads to a higher TTR and a lower INR variability. However, this is preceded by a transition period with opposite effects. An improved conversion algorithm could possibly shorten the transition period. Until then, physicians and patients should decide whether switching is worth the increased risk during the transition phase.


Assuntos
Acenocumarol/uso terapêutico , Anticoagulantes/uso terapêutico , Coeficiente Internacional Normatizado/métodos , Femprocumona/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Risco , Resultado do Tratamento , Tromboembolia Venosa/patologia , Vitamina K/antagonistas & inibidores
13.
Ann Ital Chir ; 90: 421-426, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814603

RESUMO

BACKGROUND: Non-operative management (NOM) may be particularly challenging in patients receiving synchronous antithrombotic therapy (AT). The current study examined the feasibility of NOM in patients under AT who sustained blunt splenic or hepatic injuries. METHODS: We analyzed the results of a 5-year (2010-2014) pre-decided treatment protocol, including 15 patients under AT who were treated for splenic and/or hepatic injuries at our institution. The antithrombotic therapy consisted of acenocoumarol 4 mg, acetylsalicylic acid 100 mg and clopidogrel 75 mg. Vitamin K (Vit K), Fresh frozen plasma (FFP) and Prothrombin Complex Concentrate (PCC) were transfused to patients receiving anticoagulant therapy, while platelets (PLTs) were given to patients under antiplatelet therapy if their level was excessively low. The organ injury grading scale, injury severity score (ISS), the need for blood transfusion and intensive care unit (ICU)/ high dependency unit (HDU) admission, morbidity, mortality and duration of hospital stay were also recorded. RESULTS: Ten patients fulfilled the criteria for NOM and were treated accordingly. No conversion to operative management (OM) was required (success rate 100%). Five patients were managed surgically due to hemodynamic instability and/or signs of peritonitis. Reversal of AT was attempted in all cases. CONCLUSIONS: Hemodynamically stable patients under AT with blunt hepatic or splenic injuries (grade ≤ III) and no signs of peritonitis, may be good candidates for NOM, despite their bleeding tendency. The type of AT does not seem to influence the final outcome. Reversal of AT should be stratified individually. KEY WORDS: Antithrombotic therapy, Hemodynamic stability, Non-operative management.


Assuntos
Fatores de Coagulação Sanguínea/uso terapêutico , Transfusão de Sangue , Fibrinolíticos/efeitos adversos , Hemorragia/prevenção & controle , Fígado/lesões , Plasma , Baço/lesões , Vitamina K/uso terapêutico , Ferimentos não Penetrantes/terapia , Acenocumarol/efeitos adversos , Acenocumarol/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Fatores de Coagulação Sanguínea/administração & dosagem , Terapia Combinada , Cuidados Críticos , Gerenciamento Clínico , Estudos de Viabilidade , Feminino , Fibrinolíticos/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/etiologia , Humanos , Escala de Gravidade do Ferimento , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Vitamina K/administração & dosagem , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/fisiopatologia
15.
Niger J Clin Pract ; 22(7): 1022-1025, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31293271

RESUMO

Paget-Schroetter syndrome (PSS), or effort thrombosis, refers to axillary and/or subclavian vein thrombosis associated with repetitive effort of the superior limbs, and is rare in the pediatric population. We report the case of a previously healthy 15-year-old boy who presented with a painful and swollen right arm after throwing firecrackers. Doppler ultrasound showed extensive right subclavian and axillary vein thrombosis. Anticoagulation therapy was started and had favorable evolution. We emphasize that PSS must be included in the differential diagnosis of a swollen arm.


Assuntos
Anticoagulantes/uso terapêutico , Veia Subclávia/diagnóstico por imagem , Ultrassonografia Doppler/métodos , Trombose Venosa Profunda de Membros Superiores/diagnóstico por imagem , Trombose Venosa/diagnóstico por imagem , Acenocumarol/uso terapêutico , Adolescente , Enoxaparina/uso terapêutico , Humanos , Masculino , Terapia Trombolítica , Resultado do Tratamento , Trombose Venosa Profunda de Membros Superiores/tratamento farmacológico , Trombose Venosa Profunda de Membros Superiores/etiologia , Trombose Venosa/tratamento farmacológico , Trombose Venosa/etiologia
16.
J Comp Eff Res ; 8(14): 1201-1212, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31333045

RESUMO

Aim: To compare the risk of stroke, systemic thromboembolism and bleeding, in patients initiating apixaban or acenocoumarol for the treatment of nonvalvular atrial fibrillation. Methods: An observational, retrospective study was performed using medical records of patients who initiated apixaban or acenocoumarol between 2015 and 2017. Propensity score matching was used to match patients; stroke, systemic thromboembolism, major and minor bleeding events were compared between the matched patients. Results: Patients who were prescribed apixaban had a lower rate of systemic embolism/stroke (hazard ratio [HR] = 0.54; 95% CI: 0.38-0.78; p = 0.001), minor bleeding (HR = 0.64; 95% CI: 0.52-0.79; p < 0.001) and major bleeding (HR = 0.51; 95% CI: 0.37-0.72; p < 0.001). Conclusion: Patients prescribed apixaban for the treatment of nonvalvular atrial fibrillation had lower rates of thromboembolic events and minor/major bleeding than patients on acenocoumarol.


Assuntos
Acenocumarol/efeitos adversos , Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Hemorragia/induzido quimicamente , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Acidente Vascular Cerebral/prevenção & controle , Acenocumarol/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/classificação , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Vitamina K/antagonistas & inibidores
17.
Genes (Basel) ; 10(4)2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30939847

RESUMO

There is a special interest in the implementation of pharmacogenetics in clinical practice, although there are some barriers that are preventing this integration. A large part of these pharmacogenetic tests are focused on drugs used in oncology and psychiatry fields and for antiviral drugs. However, the scientific evidence is also high for other drugs used in other medical areas, for example, in cardiology. In this article, we discuss the evidence and guidelines currently available on pharmacogenetics for clopidogrel, warfarin, acenocoumarol, and simvastatin and its implementation in daily clinical practice.


Assuntos
Anticoagulantes/efeitos adversos , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/genética , Farmacogenética , Acenocumarol/efeitos adversos , Acenocumarol/uso terapêutico , Anticoagulantes/uso terapêutico , Hidrocarboneto de Aril Hidroxilases/genética , Doenças Cardiovasculares/epidemiologia , Clopidogrel/efeitos adversos , Clopidogrel/uso terapêutico , Citocromo P-450 CYP2C9/genética , Guias como Assunto , Humanos , Medicina de Precisão , Sinvastatina/efeitos adversos , Sinvastatina/uso terapêutico , Varfarina/efeitos adversos , Varfarina/uso terapêutico
18.
J Physiol Pharmacol ; 70(1)2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-31019123

RESUMO

Unfavorable fibrin clot features have been observed in patients with venous thromboembolism (VTE). We investigated whether rivaroxaban, a direct factor Xa inhibitor, and vitamin K antagonists (VKAs) can improve plasma clot viscoelastic properties. We studied four age- and sex-matched groups: 25 healthy controls, 15 VTE patients taking rivaroxaban 20 mg/day (blood concentration, 145 (67 - 217) ng/ml), 15 VTE patients taking VKA (INR: 2 - 3), and 15 VTE patients who stopped oral anticoagulant therapy (OAT). Using a hybrid rheometier the storage (G') and loss (G") moduli were evaluated in citrated plasma after addition of 5 pmol/l tissue factor. Fiber thickness within clots was assessed using scanning electron microscopy. Higher G' but not G" was observed for VTE patients taking rivaroxaban (+34%; post hoc, P = 0.029) compared to controls. As reflected by lower G' and G", patients taking rivaroxaban (-19% and -30%; post hoc, P = 0.0013 and P < 0.0001, respectively) formed less stiff and viscous clots compared to VTE patients after OAT withdrawal, also after adjustment for fibrinogen. VTE patients treated with rivaroxaban and VKA had similar clot viscoelastic properties (post hoc, P = 0.85 for G' and P = 0.29 for G"). G' and G" correlated with plasma rivaroxaban concentrations (r = -0.67, P = 0.005 and r = -0.59, P = 0.021, respectively), and the time from the last dose of rivaroxaban intake (r = 0.59, P = 0.02 and r = 0.58, P = 0.022, respectively). G' and G" showed no association with INR in patients on VKAs. G' or G" were not associated with fibrin diameter on scanning electron microscopy images in either group. Our preliminary study shows that both rivaroxaban and VKA improve clot viscoelastic properties in VTE patients, which might contribute to their antithrombotic effects. G' and G" may reflect specific clot physical features, beyond key plasma clot characteristics, which highlights benefits from comprehensive plasma clot analysis in patients with thrombotic diseases.


Assuntos
Acenocumarol/uso terapêutico , Anticoagulantes/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Fibrina , Rivaroxabana/uso terapêutico , Trombose/fisiopatologia , Vitamina K/antagonistas & inibidores , Varfarina/uso terapêutico , Adulto , Elasticidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/fisiopatologia , Viscosidade
20.
Medicina (Kaunas) ; 55(3)2019 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-30884868

RESUMO

Ischemic stroke is a complex multifactorial disorder. Anticoagulation is a growing research area, with the main goal of preventing systemic embolization and stroke. We report the case of a 41-year-old woman with antiphospholipid syndrome who was unsuccessfully treated with Dabigatran, a new oral anticoagulant, as she developed a major stroke involving the right carotid artery, due to deep venous thrombosis with pulmonary embolism. We therefore suggest a closer monitoring of the safety and efficacy of dabigatran. Moreover, in the presence of multifactorial causes of pro-coagulation, we believe that warfarin should remain the mainstay of oral anticoagulation.


Assuntos
Síndrome Antifosfolipídica/tratamento farmacológico , Antitrombinas/efeitos adversos , Antitrombinas/uso terapêutico , Dabigatrana/efeitos adversos , Dabigatrana/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Varfarina/uso terapêutico , Aborto Espontâneo , Acenocumarol/uso terapêutico , Adulto , Antitrombinas/administração & dosagem , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/patologia , Angiografia por Tomografia Computadorizada , Dabigatrana/administração & dosagem , Feminino , Seguimentos , Humanos , Vigilância de Produtos Comercializados/métodos , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento , Trombose Venosa/complicações , Trombose Venosa/diagnóstico por imagem
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