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1.
N Engl J Med ; 385(23): 2150-2160, 2021 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-34449183

RESUMO

BACKGROUND: The role of direct oral anticoagulants as compared with vitamin K antagonists for atrial fibrillation after successful transcatheter aortic-valve replacement (TAVR) has not been well studied. METHODS: We conducted a multicenter, prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban with vitamin K antagonists in patients with prevalent or incident atrial fibrillation as the indication for oral anticoagulation after successful TAVR. The primary efficacy outcome was a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding. The primary safety outcome was major bleeding. On the basis of a hierarchical testing plan, the primary efficacy and safety outcomes were tested sequentially for noninferiority, with noninferiority of edoxaban established if the upper boundary of the 95% confidence interval for the hazard ratio did not exceed 1.38. Superiority testing of edoxaban for efficacy would follow if noninferiority and superiority were established for major bleeding. RESULTS: A total of 1426 patients were enrolled (713 in each group). The mean age of the patients was 82.1 years, and 47.5% of the patients were women. Almost all the patients had atrial fibrillation before TAVR. The rate of the composite primary efficacy outcome was 17.3 per 100 person-years in the edoxaban group and 16.5 per 100 person-years in the vitamin K antagonist group (hazard ratio, 1.05; 95% confidence interval [CI], 0.85 to 1.31; P = 0.01 for noninferiority). Rates of major bleeding were 9.7 per 100 person-years and 7.0 per 100 person-years, respectively (hazard ratio, 1.40; 95% CI, 1.03 to 1.91; P = 0.93 for noninferiority); the difference between groups was mainly due to more gastrointestinal bleeding with edoxaban. Rates of death from any cause or stroke were 10.0 per 100 person-years in the edoxaban group and 11.7 per 100 person-years in the vitamin K antagonist group (hazard ratio, 0.85; 95% CI, 0.66 to 1.11). CONCLUSIONS: In patients with mainly prevalent atrial fibrillation who underwent successful TAVR, edoxaban was noninferior to vitamin K antagonists as determined by a hazard ratio margin of 38% for a composite primary outcome of adverse clinical events. The incidence of major bleeding was higher with edoxaban than with vitamin K antagonists. (Funded by Daiichi Sankyo; ENVISAGE-TAVI AF ClinicalTrials.gov number, NCT02943785.).


Assuntos
4-Hidroxicumarinas/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Piridinas/uso terapêutico , Tiazóis/uso terapêutico , Substituição da Valva Aórtica Transcateter , Vitamina K/antagonistas & inibidores , 4-Hidroxicumarinas/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Mortalidade , Fenindiona/análogos & derivados , Fenindiona/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Piridinas/efeitos adversos , Tiazóis/efeitos adversos , Tromboembolia/prevenção & controle , Substituição da Valva Aórtica Transcateter/efeitos adversos
2.
Transfusion ; 61(10): 3008-3016, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34358342

RESUMO

BACKGROUND: Antivitamin K agent (AVK) reversal in patients with cirrhosis awaiting liver transplantation (LT) is not defined in guidelines. We investigated the effect of reversion with prothrombin complex concentrate (PCC) on intraoperative transfusion, bleeding, and safety in LT patients on AVK. STUDY DESIGN AND METHODS: In 511 patients undergoing LT, we identified 25 patients treated with AVK (AVK group) and 13 patients with incidental portal vein thrombosis (PVT) without AVK (incidental PVT group). Fifty patients who underwent LT without PVT or AVK matched by age, model for end stage of liver disease (MELD), body mass index (BMI), and cirrhosis etiology were selected as the control group. RESULTS: There were no significant differences between the three groups in intraoperative blood loss, transfusion, and postoperative bleeding. In the AVK group, there were no differences between patients who received PCC and those who did not in intraoperative blood loss, red blood cells, fibrinogen, and platelet transfusion, or postoperative bleeding. PCC use had no effect on RBC transfusion in patients who had international normalized ratio or clotting time above versus below median values of the two parameters at baseline (2.3 and 103 s, respectively). No thrombotic events were detected in patients who received PCC. DISCUSSION: These data suggest that systematic administration of PCC to revert AVK prior to LT should be reconsidered.


Assuntos
4-Hidroxicumarinas/uso terapêutico , Fatores de Coagulação Sanguínea/uso terapêutico , Indenos/uso terapêutico , Cirrose Hepática/terapia , Transplante de Fígado , Vitamina K/antagonistas & inibidores , Transfusão de Sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vitamina K/uso terapêutico
3.
Ann Hematol ; 97(1): 101-107, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29164292

RESUMO

Atrial arrhythmias (AA) induce a high rate of thromboses and require vitamin K antagonists (VKA) or direct anticoagulants (DOAC) prescriptions. Essential thrombocythemia (ET) and polycythemia vera (PV) are also pro-thrombotic diseases. The prevention of thromboses is based on the association of cytoreductive drug and low-dose aspirin (LDA). We studied the incidence and complications of AA among patients with ET or PV. We identified 96/713 patients (13.5%) carrying AA. These patients were older (median 72.1 vs. 61.3 years old, p < 0.0001). In a case-control analysis, we observed that patients with AA had a higher frequency of cardiovascular risk factors (77/96, 80% vs. 61/96, 61%; p = 0.01). A higher incidence of thromboses before and after myeloproliferative neoplasm (MPN) diagnosis was seen in this group: 26/96, 27.1% vs. 14/96, 14.6% (p = 0.03) and 34/96, 35% vs. 18/96, 18.8% (p = 0.009). Most of the events were arterial (82 vs. 61%, p = 0.09). This translates into a shorter thrombosis-free survival (11.0 vs. 21.6 years, p = 0.01). Continuation of LDA in this situation exposed patients to more thrombotic events (p = 0.04) but VKA did not seem to be good anticoagulant drugs either. The association of AA and MPN is more frequent than expected. AA clearly increased the thrombotic risk of these patients. Anticoagulant drugs should be carefully managed between cardiologists and hematologists. Association of LDA and VKA or the role of DOAC in such population should be rapidly discussed to reduce the thrombotic rate.


Assuntos
Arritmias Cardíacas/epidemiologia , Transtornos Mieloproliferativos/epidemiologia , Trombose/epidemiologia , 4-Hidroxicumarinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Feminino , França/epidemiologia , Humanos , Incidência , Indenos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/complicações , Fatores de Risco , Trombose/tratamento farmacológico , Vitamina K/antagonistas & inibidores , Vitamina K/uso terapêutico
4.
J Clin Pharm Ther ; 43(1): 52-58, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28921594

RESUMO

WHAT IS KNOWN AND OBJECTIVE: The international normalized ratio (INR) is widely used to monitor patients on vitamin K antagonists. This study aimed to assess the agreement of INR values obtained with different thromboplastin/instrument combinations. MATERIAL AND METHODS: International normalized ratio was determined on plasmas from 330 patients undergoing antivitamin K treatment (with acenocoumarol), using two calibration methods and four reagent/instrument combinations: Both Neoplastine CI and Neoplastine CI Plus on STA-R instrument from Diagnostica STAGO, Asnières, France; and both Thromborel S and Innovin on SYSMEX 2100i instrument from Siemens Health Care Diagnostics, Marbung, Germany. The agreement analysis was done using the Bland-Altman plot and the Cohen Kappa coefficient. RESULTS: The mean of the differences between the INR values and the limits of agreement were -0.07 [-0.51 to 0.38] for the Neoplastine CI plus and Neoplastine CI reagents, -0.08 [-1.18 to 1.03] for the Thromborel S and Innovin reagents when the INR was calculated, -0.1 [-1.15 to 0.95] for the Thromborel S and Innovin reagents when the INR was directly calibrated and -0.1 [-0.7 to 0.5] for the Neoplastine CI plus and Thromborel S. Cohen's kappa coefficients were 0.94, 0.76, 0.85 and 0.82, respectively. NEW FINDINGS AND CONCLUSION: The agreement between the four reagent/instrument combinations was high enough to classify patients as inefficaciously or efficaciously anticoagulated. The data interpretation should always be related to the clinical purpose.


Assuntos
4-Hidroxicumarinas/uso terapêutico , Indenos/uso terapêutico , Indicadores e Reagentes/uso terapêutico , Coeficiente Internacional Normatizado/métodos , Tromboplastina/uso terapêutico , Vitamina K/antagonistas & inibidores , Acenocumarol/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Calibragem , França , Alemanha , Voluntários Saudáveis , Humanos , Vitamina K/metabolismo , Vitamina K/uso terapêutico
5.
Tunis Med ; 96(3): 182-186, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30325485

RESUMO

INTRODUCTION: Vitamin K antagonists (VKA) are currently the most prescribed oral anticoagulant treatment in Tunisia. Despite the standardization of biological monitoring and the better definition of therapeutic objectives, their side effects are a frequent reason for hospitalization. AIM: To evaluate patients' knowledge about their VKA treatment. METHODS: We realized a cross-sectional descriptive study in the Cardiology Department of HabibThameur Hospital from September to October 2016. A questionnaire consisting of 14 items was used in a semi-directed interview in order to assess patients' knowledge on their VKA treatment. RESULTS: Our study included one hundred patients. Mean age was 61 ± 12 years and sex ratio of 1.8. Forty-eight per cent were illiterate. The median duration of AVK intake was 5 years. Atrial fibrillation (AF) was the most frequent indication (57%). Eighty percent of patients had more than five correct answers on the eight items of knowledge: VKA's name (96%), tablet description (93%), dose (99%), time (94%), VKA's effect (70%), INR (56%), treatment's risk (49%) and the target INR (20%). Twenty-two percent had more than four correct answers on the 6 items of know-how: what to do in case of haemorrhage (70%), what to do in case of oblivion (45%), interactions precautions to be observed with food (13%), activities advised against (49%) and medical procedures advised against (27%). In multivariate analysis, only prior VKA information was significantly associated with a better knowledge of VKA (p = 0.027). CONCLUSION: Our patients' knowledge on their VKA treatment was insufficient to ensure the safety and efficacy of treatment. The creation of a therapeutic education program on is therefore necessary to reduce the iatrogenic risk of this treatment.


Assuntos
4-Hidroxicumarinas/uso terapêutico , Anticoagulantes/uso terapêutico , Indenos/uso terapêutico , Conhecimento , Vitamina K/antagonistas & inibidores , 4-Hidroxicumarinas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Atitude Frente a Saúde , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/epidemiologia , Estudos Transversais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Escolaridade , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Indenos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Vitamina K/efeitos adversos , Vitamina K/uso terapêutico
6.
Rev Med Suisse ; 13(560): 911-915, 2017 Apr 26.
Artigo em Francês | MEDLINE | ID: mdl-28727359

RESUMO

Oral anticoagulation with vitamin K antagonists (VKA) was the cornerstone of stroke prevention in atrial fibrillation (AF). This review article presents the state of the art, with regard to the treatment options developed over the past few years, the new oral anticoagulants (NOAC). A search in PubMed for relevant published studies has been performed. Dabigatran and apixaban were superior to warfarin to reduce stroke risk or systemic embolism ; dabigatran, rivaroxaban and edoxaban were non-inferior. All NOAC are globally non-inferior to warfarin for stroke prevention in non-valvular AF and they have a superior safety profile, with a reduced intracranial bleeding risk. They are now the first choice for treatment.


Les antagonistes de la vitamine K (AVK) ont été pendant longtemps la référence comme prévention de l'accident vasculaire cérébral (AVC) chez les patients souffrant de fibrillation auriculaire (FA). Cet article de revue propose une mise à jour des options thérapeutiques développées ces dernières années, à savoir les nouveaux anticoagulants oraux (NACO). Une recherche des études pertinentes a été effectuée dans PubMed. Il apparaît ainsi que le dabigatran et l'apixaban sont supérieurs à la warfarine pour réduire les AVC et les embolies systémiques ; le dabigatran, le rivaroxaban et l'édoxaban sont non inférieurs. Tous les NACO sont donc globalement non inférieurs à la warfarine pour prévenir les AVC dans la FA non valvulaire et ils ont un profil de sécurité supérieur, avec un moindre risque d'hémorragie intracrânienne. Ils représentent maintenant le traitement de premier choix.


Assuntos
Fibrilação Atrial/terapia , Acidente Vascular Cerebral/prevenção & controle , 4-Hidroxicumarinas/uso terapêutico , Administração Oral , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Drogas em Investigação/administração & dosagem , Humanos , Indenos/uso terapêutico , Acidente Vascular Cerebral/etiologia , Vitamina K/antagonistas & inibidores , Vitamina K/uso terapêutico
7.
Rev Med Brux ; 36(4): 365-72, 2015 Sep.
Artigo em Francês | MEDLINE | ID: mdl-26591325

RESUMO

Atrial fibrillation (AF) increases the risk of mortality and stroke. The prevention of these complications is based on oral anticoagulants that are more efficient than salycilates. As compared with antivitamins K agents, new oral anticoagulants are promising for patients presenting non valvular atrial fibrillation because of lower cerebral hemorragic risk (with respect of assessment of renal function and therapeutic compliance). Available studies and recommendations are presented.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Drogas em Investigação/uso terapêutico , 4-Hidroxicumarinas/uso terapêutico , Humanos , Indenos/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Vitamina K/antagonistas & inibidores , Vitamina K/uso terapêutico
8.
Bull Acad Natl Med ; 197(8): 1561-70; discussion 1570-1, 2013 Nov.
Artigo em Francês | MEDLINE | ID: mdl-26021177

RESUMO

The indications for antithrombotic treatment with vitamin K antagonists are now relatively precise, but management of this treatment is often difficult in clinical practice and be set by problems such as unstable hypocoagulability, an increased bleeding risk, interactions with other therapies and pathologies, and high-level vitamin K intake in the diet. Rigorous and accurate information of the patient and family, along with regular and frequent control of the international normalized ratio (INR), are essential for the safety and efficacy of this treatment. Some physicians cite an excessive bleeding risk as one reason for withholding oral anticoagulation therapy from older patients with atrial fibrillation. Indeed, with the increasing aging of the population, and poor therapeutic observance, there is an increased risk of hemorragic adverse effects. However, vitamin K antagonists are associated with a significant reduction in embolic events, and recent guidelines recommend their prescription for elderly patients with atrial fibrillation. Their impact on the risk of thromboembolic events is well documented, with better results than those obtained with new oral anticoagulants. Education of the patient and family, and close cooperation between the patient, family, physician and entire medical team, are essential for the safety and efficacy of this treatment.


Assuntos
4-Hidroxicumarinas/uso terapêutico , Anticoagulantes/uso terapêutico , Monitoramento de Medicamentos , Prescrições de Medicamentos , Indenos/uso terapêutico , Padrões de Prática Médica , Trombose/tratamento farmacológico , Vitamina K/antagonistas & inibidores , Monitoramento de Medicamentos/normas , Humanos , Monitorização Fisiológica/métodos , Padrões de Prática Médica/normas , Resultado do Tratamento , Vitamina K/uso terapêutico
9.
Rev Stomatol Chir Maxillofac ; 113(3): 143-7, 2012 Jun.
Artigo em Francês | MEDLINE | ID: mdl-22537515

RESUMO

OBJECTIVE: Assessment of a local hemostasis with a compressive, extemporaneous gutter glued to the alveolar crest after tooth avulsion in patients under anticoagulant and/or platelet aggregation inhibitors, and economical impact of this technique. MATERIAL AND METHOD: Ninety-seven tooth extractions were performed in patients under AVK and/or anti-platelet drugs. The interventions were consecutive and concerned 251 teeth (138 different alveolar sites). The extraction alveolus was protected by an absorbable oxycellulose membrane coated with sterilized cyanoacrylate adhesive for medical use. This procedure was used with all patients, whatever the hemorrhagic risk (the only inclusion criterion was INR less than 4 for patients under AVK). All procedures were performed under local anesthesia. RESULTS: There was one hemorrhagic complication (0.72%) due to mechanical gutter destruction by an antagonist tooth. The adhesive did not run, there was no tissue necrosis, and no wound infection requiring gutter removal. DISCUSSION: This local hemostasis procedure is reliable. It may be an alternative to substitution of heparin, without or with hospitalization. This procedure, requiring modification of treatment, greatly decreases healthcare costs. Contra-indications include the presence of an antagonist tooth harmful for the gutter, and patients with impaired consciousness or tongue dyspraxia.


Assuntos
Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/terapia , Cianoacrilatos/administração & dosagem , Hemostasia Cirúrgica/métodos , Inibidores da Agregação Plaquetária/uso terapêutico , Extração Dentária , 4-Hidroxicumarinas/uso terapêutico , Administração Tópica , Transtornos da Coagulação Sanguínea/epidemiologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/uso terapêutico , Cianoacrilatos/química , Hemostasia Cirúrgica/instrumentação , Humanos , Indenos/uso terapêutico , Hemorragia Pós-Operatória/epidemiologia , Hemorragia Pós-Operatória/prevenção & controle , Estudos Retrospectivos , Adesivos Teciduais/administração & dosagem , Adesivos Teciduais/química , Extração Dentária/efeitos adversos , Extração Dentária/métodos , Extração Dentária/estatística & dados numéricos , Vitamina K/antagonistas & inibidores , Vitamina K/uso terapêutico
10.
Rev Med Suisse ; 8(330): 462-5, 2012 Feb 29.
Artigo em Francês | MEDLINE | ID: mdl-22452132

RESUMO

As chronic kidney disease (CKD) is a contraindication to the use of the new anticoagulants, the vitamin K antagonists (VKA) are still valid in patients with CKD, though their use may be harmful. During overanticoagulation, some patients can develop acute kidney injury (AKI), especially those with CKD, by obstruction of the renal tubules and Bowman's spaces by erythrocytes. In addition, VKA increase atherogenesis through vitamin K deficiency, which is essential for the carboxylation of proteins that inhibit calcification of vessels. Eventually, hemodialysed patients under VKA have an increased risk of stroke, especially those over 75 years of age. Therefore anticoagulation with VKA in patients with CKD should be carefully implemented and its monitoring more frequent than in non-CKD patients.


Assuntos
4-Hidroxicumarinas/efeitos adversos , 4-Hidroxicumarinas/uso terapêutico , Injúria Renal Aguda/induzido quimicamente , Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Indenos/efeitos adversos , Indenos/uso terapêutico , Insuficiência Renal Crônica/complicações , Vitamina K/antagonistas & inibidores , Injúria Renal Aguda/epidemiologia , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Aterosclerose/induzido quimicamente , Aterosclerose/epidemiologia , Transtornos da Coagulação Sanguínea/epidemiologia , Transtornos Cerebrovasculares/induzido quimicamente , Transtornos Cerebrovasculares/epidemiologia , Cumarínicos/efeitos adversos , Humanos , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/epidemiologia , Vitamina K/efeitos adversos , Vitamina K/uso terapêutico , Varfarina/efeitos adversos
11.
Nutrients ; 13(10)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34684491

RESUMO

Vitamin K dependent proteins (VKDP), such as hepatic coagulation factors and vascular matrix Gla protein (MGP), play key roles in maintaining physiological functions. Vitamin K deficiency results in inactive VKDP and is strongly linked to vascular calcification (VC), one of the major risk factors for cardiovascular morbidity and mortality. In this study we investigated how two vitamin K surrogate markers, dephosphorylated-undercarboxylated MGP (dp-ucMGP) and protein induced by vitamin K absence II (PIVKA-II), reflect vitamin K status in patients on hemodialysis or with calcific uremic arteriolopathy (CUA) and patients with atrial fibrillation or aortic valve stenosis. Through inter- and intra-cohort comparisons, we assessed the influence of vitamin K antagonist (VKA) use, vitamin K supplementation and disease etiology on vitamin K status, as well as the correlation between both markers. Overall, VKA therapy was associated with 8.5-fold higher PIVKA-II (0.25 to 2.03 AU/mL) and 3-fold higher dp-ucMGP (843 to 2642 pM) levels. In the absence of VKA use, non-renal patients with established VC have dp-ucMGP levels similar to controls (460 vs. 380 pM), while in HD and CUA patients, levels were strongly elevated (977 pM). Vitamin K supplementation significantly reduced dp-ucMGP levels within 12 months (440 to 221 pM). Overall, PIVKA-II and dp-ucMGP showed only weak correlation (r2 ≤ 0.26) and distinct distribution pattern in renal and non-renal patients. In conclusion, VKA use exacerbated vitamin K deficiency across all etiologies, while vitamin K supplementation resulted in a vascular VKDP status better than that of the general population. Weak correlation of vitamin K biomarkers calls for thoughtful selection lead by the research question. Vitamin K status in non-renal deficient patients was not anomalous and may question the role of vitamin K deficiency in the pathogenesis of VC in these patients.


Assuntos
Biomarcadores/sangue , Proteínas de Ligação ao Cálcio/sangue , Proteínas da Matriz Extracelular/sangue , Precursores de Proteínas/sangue , Calcificação Vascular/sangue , Deficiência de Vitamina K/sangue , Vitamina K/sangue , 4-Hidroxicumarinas/uso terapêutico , Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/complicações , Fibrilação Atrial/sangue , Fibrilação Atrial/complicações , Doenças Cardiovasculares/etiologia , Estudos de Coortes , Suplementos Nutricionais , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Indenos/uso terapêutico , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Protrombina , Diálise Renal/efeitos adversos , Uremia/sangue , Uremia/complicações , Calcificação Vascular/complicações , Vitamina K/antagonistas & inibidores , Vitamina K/uso terapêutico , Deficiência de Vitamina K/complicações , Proteína de Matriz Gla
12.
Curr Opin Pulm Med ; 16(5): 432-6, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20671514

RESUMO

PURPOSE OF REVIEW: There is some uncertainty about the management of pulmonary embolism in nonagenarians. RECENT FINDINGS: Immobility plays an important role in the pathogenesis of venous thromboembolism in the elderly. Of 858 nonagenarians with acute venous thromboembolism enrolled in Registro Informatizado de la Enfermedad TromboEmbolica venosa registry, 41% had recent immobility and only 7.7% had recent surgery. Comorbidity is common: 19% of patients had chronic heart failure, 9.8% chronic lung disease, 14% cancer, and 63% had abnormal creatinine levels. Most (92%) of the patients were initially treated with low-molecular-weight heparin and then 46% switched to antivitamin K drugs. During follow-up, the proportion of patients who developed recurrent venous thromboembolism (4.9%) or major bleeding complications (6.2%) was similar, but the 5.9% of fatal pulmonary embolisms by far exceeded the 2.2% of fatal bleeding events. The most common clinical symptoms are isolated dyspnea and syncope, and presentation as pulmonary infarction (with hemoptysis and pleuritic chest pain) is rare. SUMMARY: In patients aged at least 90 years presenting with acute pulmonary embolism, the incidence of fatal pulmonary embolism by far outweighs the incidence of fatal bleeding, and pulmonary embolism is the most common cause of death. Thus, there seems to be more reason to be concerned about fatal pulmonary embolism than about bleeding in elderly patients presenting with pulmonary embolism.


Assuntos
Heparina de Baixo Peso Molecular/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/epidemiologia , 4-Hidroxicumarinas/efeitos adversos , 4-Hidroxicumarinas/uso terapêutico , Fatores Etários , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Feminino , Hemorragia/epidemiologia , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Incidência , Indenos/efeitos adversos , Indenos/uso terapêutico , Masculino , Fatores de Risco , Espanha , Vitamina K/efeitos adversos , Vitamina K/antagonistas & inibidores , Vitamina K/uso terapêutico
14.
Ann Biol Clin (Paris) ; 78(6): 655-664, 2020 Dec 01.
Artigo em Francês | MEDLINE | ID: mdl-33361016

RESUMO

The lack of quality control for patient point-of-care (POC) INR devices is an issue that has led the French health authorities to make recommendations: a laboratory INR (lab INR) has to be performed at the same time as the POC INR every 6 months. However, the differences observed between the two INRs, POC and lab INRs, are not necessarily due to a failure of the POC INR device. We present here a review of the different causes of discrepancies between INR results, which are the basis of the proposals of the Groupe français d'études sur l'hémostase et la thrombose (GFHT) on the management of lab and POC INR discrepancies. Pre-analytical conditions may account for discrepancies (sampling, transport and storage conditions), as well as analytical factors (mainly the nature of the thromboplastin used) and the clinical context (inflammatory or autoimmune diseases, polycythaemia...). The interpretation of INR discrepancies is not always easy and these proposals aim at standardizing the procedure to be followed in order to make the most appropriate decision for the patient.


Assuntos
Técnicas de Laboratório Clínico/normas , Coeficiente Internacional Normatizado/métodos , Coeficiente Internacional Normatizado/normas , Kit de Reagentes para Diagnóstico/normas , Autoteste , 4-Hidroxicumarinas/uso terapêutico , Anticoagulantes/uso terapêutico , França , Humanos , Indenos/uso terapêutico , Laboratórios/normas , Ensaio de Proficiência Laboratorial/métodos , Ensaio de Proficiência Laboratorial/normas , Padrões de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Sociedades Científicas/normas , Trombose/sangue , Trombose/tratamento farmacológico , Vitamina K/antagonistas & inibidores , Vitamina K/uso terapêutico
15.
Ann Biol Clin (Paris) ; 78(2): 157-173, 2020 04 01.
Artigo em Francês | MEDLINE | ID: mdl-32319944

RESUMO

The main objective of our study was to carry out a statement of the knowledge and the management of the VKA by the General Practitioners (GPs) of Normandy and to evaluate their experience of the use of DOA with a questionnaire; 471 of the 1951 GPs requested responded. When the INR was stable in a patient affected with atrial fibrillation, the GPs participating dosed it again 4 weeks later, modified the dosage when the INR was below 1.9 or upper 3.2. The risk of stroke was overestimated to 6.2% per year with fluindione and to 31.5% without curative anticoagulation. The mean TTR was overstated to 84%. When the INR was at 4.4, the risk of serious cerebral bleeding was overestimated at 12.4%. 80.26% of the GPs skipped the next dose and 11.25% controlled the INR the day after. So, few GPs used the HAS protocol. After the INR decreased to 3.6, the GPs diminished the dose of 14.62%. 70% of the GPs, responded using only their experience for AVK management. Fluindione was the most to use VKA by 52.7% of them although 24.42% thought it was the most effective. The majority of GPs thought the DOA were a least as effective than the VKA, without being responsible of more bleeding (77.92%) and improved the quality of life of the patients (88.54%). Although the DOA's prescriptions increase, the improvement of the VKA management have to stay a concern for the GPs.


Assuntos
4-Hidroxicumarinas/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fidelidade a Diretrizes/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Indenos/uso terapêutico , Coeficiente Internacional Normatizado , Médicos de Atenção Primária , Vitamina K/antagonistas & inibidores , Adulto , Fibrilação Atrial/sangue , Coagulação Sanguínea/efeitos dos fármacos , Estudos Transversais , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Monitorização Fisiológica/normas , Médicos de Atenção Primária/normas , Médicos de Atenção Primária/estatística & dados numéricos , Padrões de Prática Médica/normas , Padrões de Prática Médica/estatística & dados numéricos , Inquéritos e Questionários , Vitamina K/uso terapêutico
16.
Neth J Med ; 77(3): 98-108, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31012427

RESUMO

INTRODUCTION: The antiphospholipid syndrome (APS) is defined by the occurrence of venous and/or arterial thrombosis and/or pregnancy-related morbidity, combined with the presence of antiphospholipid antibodies (aPL) and/or a lupus anticoagulant (LAC). Large, controlled, intervention trials in APS are limited. This paper aims to provide clinicians with an expert consensus on the management of APS. METHODS: Relevant papers were identified by literature search. Statements on diagnostics and treatment were extracted. During two consensus meetings, statements were discussed, followed by a Delphi procedure. Subsequently, a final paper was written. RESULTS: Diagnosis of APS includes the combination of thrombotic events and presence of aPL. Risk stratification on an individual base remains challenging. 'Triple positive' patients have highest risk of recurrent thrombosis. aPL titres > 99th percentile should be considered positive. No gold standard exists for aPL testing; guidance on assay characteristics as formulated by the International Society on Thrombosis and Haemostasis should be followed. Treatment with vitamin K-antagonists (VKA) with INR 2.0-3.0 is first-line treatment for a first or recurrent APS-related venous thrombotic event. Patients with first arterial thrombosis should be treated with clopidogrel or VKA with target INR 2.0-3.0. Treatment with direct oral anticoagulants is not recommended. Patients with catastrophic APS, recurrent thrombotic events or recurrent pregnancy morbidity should be referred to an expert centre. CONCLUSION: This consensus paper fills the gap between evidence-based medicine and daily clinical practice for the care of APS patients.


Assuntos
Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/terapia , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/terapia , 4-Hidroxicumarinas/uso terapêutico , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/complicações , Técnica Delphi , Feminino , Humanos , Indenos/uso terapêutico , Gravidez , Complicações na Gravidez/imunologia , Trombose/imunologia , Trombose/terapia , Vitamina K/antagonistas & inibidores , Vitamina K/uso terapêutico
17.
Tunis Med ; 97(3): 432-437, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31729717

RESUMO

BACKGROUND: Atrial fibrillation is the most common heart rhythm disorder in the general population. It is associated with increased cardiovascular morbidity and mortality. Given this risk, anticoagulant therapy is vital. AIM: To estimate the incidence of thromboembolic and hemorrhagic events in patients with Atrial fibrillation and treated by oral anticoagulant in a cardiology department. METHODS: We carried out an observational longitudinal study over a period of three years (January 2013 - December 2015) in the external consultation of cardiology of Farhat Hached hospital of Sousse. Pre-established individual records were used as a source and tool for data collection. RESULTS: Overall, 200 patients were eligible. Forty-nine percent had valvular atrial fibrillation. After an average follow-up of 2.6 years, 15 thromboembolic events were noted affecting 13 patients (6.5%), with an incidence of 2.8%. We found a significant association between TTR <50% and the occurrence of stroke and transient ischemic events. Half of the patients had minor bleeding and 9.5% had major bleeding, with an incidence of 3.6%. No significant correlation between these accidents and the TTR was found. In addition, 9.5% of patients were hospitalized for international normalized ratio equilibration. They were mainly patients with valvular atrial fibrillation (72%) (p = 0.002). CONCLUSION: Anticoagulant therapy with anti-vitamin-K remains the most adequate treatment. Thus, a well-conducted treatment ensures a reduction in thromboembolic risk and minimizes the occurrence of hemorrhages inherent to this therapy. Therefore, an assessment of the quality of anticoagulation is essential.


Assuntos
4-Hidroxicumarinas/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Hemorragia/epidemiologia , Indenos/uso terapêutico , Tromboembolia/epidemiologia , Vitamina K/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Tromboembolia/prevenção & controle , Tunísia/epidemiologia , Vitamina K/uso terapêutico
18.
J Trace Elem Med Biol ; 22(2): 100-11, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18565422

RESUMO

The new cerium(III), lanthanum(III) and neodymium(III) complexes were synthesized in view of their application as cytotoxic agents. The complexes were characterized by different physicochemical methods: elemental analysis, mass spectrometry, (1)H NMR, (13)C NMR and IR spectroscopy. The spectra of the complexes were interpreted on the basis of comparison with the spectrum of the free ligand. The vibrational analysis showed that in the complexes the ligand coordinates to the metal ion through both deprotonated hydroxyl groups, however participation of the carbonyl groups in the coordination to the metal ion was also suggested. Geometry optimization of 3,3'-(ortho-pyridinomethylene)di-[4-hydroxycoumarin] H(2)(o-pyhc), (H(2)L) and its dianionic forms, o-pyhc(2-), (L(2-)) were carried out at AM1 and PM3 levels as well as using density functional theory with Becke's three parameter hybrid method and correlation functional of Lee, Yang and Parr (B3LYP) with 6-31G(d) basis set. The optimized geometries of the neutral ligand isomers were stabilized by two asymmetrical intramolecular O-H...O hydrogen bonds (HBs). The conformational search showed four low-energy dianionic species (o-pyhc(2-)) on the potential energy surface. Molecular electrostatic potential calculations showed that the most preferred sites for electrophilic attack in H(2)(o-pyhc) and o-pyhc(2-) are the carbonyl oxygen atoms. The evaluation of the cytotoxic activity of the novel lantanide complexes on HL-60 myeloid cells revealed, that they are potent cytotoxic agents. The cerium complex was found to exhibit superior activity in comparison to the lanthanum, and neodymium species, the latter being the least active. Taken together our data give us a reason to conclude that the newly synthesized lanthanide complexes should be a subset to further more detailed pharmacological and toxicological evaluation.


Assuntos
4-Hidroxicumarinas/química , Antineoplásicos/química , Cério/química , Neodímio/química , 4-Hidroxicumarinas/uso terapêutico , Animais , Antineoplásicos/farmacologia , Cério/farmacologia , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células HL-60/efeitos dos fármacos , Humanos , Estrutura Molecular , Neodímio/farmacologia , Ressonância Magnética Nuclear Biomolecular , Eletricidade Estática
19.
Rev Med Interne ; 39(5): 321-325, 2018 May.
Artigo em Francês | MEDLINE | ID: mdl-29550092

RESUMO

INTRODUCTION: Vitamin K antagonists (VKA) are drugs with a major risk of side effect. Guidelines have been published in 2008 by the Haute Autorité de santé (HAS) concerning the management of an excessively elevated INR ratio. Our research aimed to assess physicians' adherence to those guidelines. METHODS: We realized a retrospective, multicentric study. One hundred and ten cases of excessively elevated INR ratio were identified and analyzed. RESULTS: Overall physicians adherence was 58%. However, patients with the most elevated INR, i.e., INR>6, were treated according to guidelines in only 33% of the cases. The use of vitamin K was the major source of mistakes. The rate of mortality was 20%. CONCLUSION: Adherence to HAS guidelines seems finally limited. It is necessary to put in place procedures to secure the behavior of physicians.


Assuntos
4-Hidroxicumarinas/efeitos adversos , Anticoagulantes/efeitos adversos , Fidelidade a Diretrizes/estatística & dados numéricos , Indenos/efeitos adversos , Coeficiente Internacional Normatizado/métodos , Vitamina K/antagonistas & inibidores , 4-Hidroxicumarinas/uso terapêutico , Idoso , Anticoagulantes/uso terapêutico , Overdose de Drogas , Feminino , França , Humanos , Indenos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Médicos , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Vitamina K/efeitos adversos , Vitamina K/uso terapêutico
20.
J Photochem Photobiol B ; 189: 124-137, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30342308

RESUMO

In the progress of small molecule as drug candidates, 4-hydroxycoumarin based compounds bearing a crucial place as potent antibiotic agents with appreciable safety in drug invention. Being synthetically and easily obtainable, 4-hydroxycoumarin related compounds with planar structure have been promoted predominantly as DNA targeting agent. Nevertheless, here we elucidate the synthesis, characterization and theoretical study of bio-active small molecule 4-hydroxy-3,4'-bichromenyl-2,2'-dione (4HBD). Then we have illuminated the binding interactions of 4HBD with calf thymus DNA (ctDNA), which is particularly designed for biological application. Extensive investigations of the binding of 4HBD with ctDNA are provided by utilizing multi-spectroscopic and molecular docking approaches, including UV-vis absorbance, steady-state, time-resolved fluorescence spectroscopy and circular dichroism study. The calculated binding and quenching constant value from quantitative data analysis of absorption and emission spectroscopy shows that 4HBD binds to the ctDNA groove. Further confirmation of the same is found by comparative displacement and iodide quenching studies. Negative enthalpy, negative free energy and positive entropy change imply a hydrophobic force monitors the association of 4HBD with the biomacromolecule. Interestingly the small molecule (4HBD) shows potential anti-bacterial activity against the model pathogenic gram-negative (Escherichia coli and Pseudomonas aeruginosa) and gram-positive (Bacillus subtilis and Staphylococcus aureus) bacteria. The noncytotoxic nature of the 4HBD is demonstrated in vitro with the help of MTT assay by normal kidney epithelial (NKE), breast cancer cells (MCF-7) and human prostate cancer cell (PC3) lines. Hemolytic assay exhibits insignificant hemolysis of human erythrocyte cells at the minimum inhibitory concentration (MIC) of these tested bacteria. In this regard the present invention of 4-hydroxycoumarin based antimicrobial and noncytotoxic 4HBD molecule holds future promise in the development of new antibiotics.


Assuntos
4-Hidroxicumarinas/metabolismo , Antibacterianos/farmacologia , Biopolímeros/metabolismo , 4-Hidroxicumarinas/síntese química , 4-Hidroxicumarinas/uso terapêutico , Bactérias/efeitos dos fármacos , Sítios de Ligação , Morte Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , DNA/metabolismo , Humanos , Simulação de Acoplamento Molecular , Análise Espectral
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