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1.
Clin Appl Thromb Hemost ; 27: 10760296211039288, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595937

RESUMO

Coronavirus disease 2019 (COVID-19) is a systemic disease that can be life-threatening involving immune and inflammatory responses, and that can result in potentially lethal complications, including venous thrombo-embolism (VTE). Forming an integrative approach to thrombo-prophylaxis and coagulation treatment for COVID-19 patients ensues. We aim at reviewing the literature for anticoagulation in the setting of COVID-19 infection to provide a summary on anticoagulation for this patient population. COVID-19 infection is associated with a state of continuous inflammation, which results in macrophage activation syndrome and an increased rate of thrombosis. Risk assessment models to predict the risk of thrombosis in critically ill patients have not yet been validated. Currently published guidelines suggest the use of prophylactic intensity over intermediate intensity or therapeutic intensity anticoagulant for patients with critical illness or acute illness related to COVID-19 infection. Critically ill COVID-19 patients who are diagnosed with acute VTE are considered to have a provoking factor, and, therefore, treatment duration should be at least 3 months. Patients with proximal deep venous thrombosis or pulmonary embolism should receive parenteral over oral anticoagulants with low-molecular-weight heparin or fondaparinux preferred over unfractionated heparin. In patients with impending hemodynamic compromise due to PE, and who are not at increased risk for bleeding, reperfusion may be necessary. Internists should remain updated on new emerging evidence regarding anticoagulation for COVID-19 patients. Awaiting these findings, we invite internists to perform individualized decisions that are unique for every patient and to base them on clinical judgment for risk assessment.


Assuntos
Anticoagulantes/uso terapêutico , COVID-19/complicações , SARS-CoV-2 , Trombofilia/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Consenso , Estado Terminal , Gerenciamento Clínico , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fondaparinux/efeitos adversos , Fondaparinux/uso terapêutico , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Pacientes Internados , Masculino , Guias de Prática Clínica como Assunto , Gravidez , Complicações Hematológicas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/sangue , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/etiologia , Embolia Pulmonar/prevenção & controle , Risco , Trombofilia/etiologia , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Trombose Venosa/tratamento farmacológico , Trombose Venosa/etiologia , Trombose Venosa/prevenção & controle
2.
Medicine (Baltimore) ; 100(37): e27251, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34664871

RESUMO

BACKGROUND: This study aims to analyze and evaluate the difference in efficacy between left atrial appendage closure (LAAC) and oral anticoagulants (OA) in preventing stroke in patients with non-valvular atrial fibrillation (NVAF) through the method of meta-analysis. The purpose is to provide for the prevention of stroke in patients with NVAF valuable treatment guidance. METHODS: This study is a comprehensive collection of randomized controlled studies of LAAC and OA in the prevention of stroke in patients with NVAF, and searches PubMed, Embase, the Cochrane Library, Web of Science, CNKI, SinoMed, VIP Database, WANFANG Database, and other Chinese and English databases by combining subject words with free words, and the retrieval time is from the establishment of each database to June 1, 2021. At the same time, searching the included literature and literature of related reviews by manual. Two researchers independently conduct literature screening and quality evaluation. Statistical software RevMan 5.3 and Stata 12.0 were used for meta-analysis. RESULTS: This study evaluating the difference in efficacy between LAAC and OA in preventing stroke in patients with NVAF will be published in high-quality medical academic journals. CONCLUSION: This study will give the best treatment strategy to prevent stroke in patients with NVAF, and provide some reference for clinical medical staff.OSF registration number: DOI 10.17605/OSF.IO/2UXPA (https://osf.io/2uxpa).


Assuntos
Apêndice Atrial/cirurgia , Fibrilação Atrial/tratamento farmacológico , Procedimentos Cirúrgicos Cardíacos/normas , Protocolos Clínicos , Acidente Vascular Cerebral/prevenção & controle , Apêndice Atrial/fisiopatologia , Fibrilação Atrial/complicações , Inibidores do Fator Xa/normas , Inibidores do Fator Xa/uso terapêutico , Átrios do Coração/efeitos dos fármacos , Humanos , Metanálise como Assunto , Acidente Vascular Cerebral/tratamento farmacológico , Revisões Sistemáticas como Assunto , Resultado do Tratamento
3.
BMJ Case Rep ; 14(10)2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34649859

RESUMO

Dabigatran, a novel oral anticoagulant, is a direct thrombin inhibitor and is being increasingly used owing to the advantage of dosing without the need for laboratory monitoring. While extensive skin necrosis is known to be associated with oral anticoagulants such as warfarin and factor Xa inhibitors, dabigatran toxicity typically manifests with bleeding, especially in the elderly. We describe a 70-year-old woman who was prescribed dabigatran for the treatment of unprovoked deep venous thrombosis. She developed bleeding diathesis along with extensive skin necrosis and acute kidney injury shortly after commencing the drug. Haemodialysis was given in view of dabigatran toxicity and complications of kidney dysfunction which resolved promptly over a week. However, the patient succumbed to severe sepsis from secondary skin infections. It is crucial to closely monitor for signs of dabigatran toxicity, especially in the elderly patients.


Assuntos
Anticoagulantes , Dabigatrana , Idoso , Anticoagulantes/efeitos adversos , Dabigatrana/efeitos adversos , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , Necrose/induzido quimicamente , Varfarina
4.
Acta Med Indones ; 53(3): 308-314, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34611070

RESUMO

COVID-19 became a widespread infectious disease in late 2019. Indonesia currently has the highest COVID-19 mortality rate in Asia, between 4-5 percent. Interestingly, COVID-19-associated coagulopathy characterized by an increase of several procoagulant factor levels, including fibrinogen and D-dimer, that has been associated with higher mortality and unfavorable outcomes. We report a case of a 30-year-old male admitted to the hospital with a profuse vomiting and worsening fever, cough and shortness of breath, and was diagnosed with COVID-19-associated coagulopathy. Seven days after admission, he became deteriorated with significant reduction of oxygen saturation and his coagulation parameter levels were increased with highly suspicion of pulmonary embolism. He was treated with azithromycin, isoprinosine, lopinavir, and fondaparinux with thromboprophylaxis dosage since admission. The role of increased fondaparinux dosage at the time of clinical deterioration was then followed by clinical improvement and reduced D-dimer level. Anticoagulant therapy, mainly with fondaparinux, showed a better prognosis in patients with markedly elevated D-Dimer. Fondaparinux needs to be monitored appropriately to prevent bleeding and adverse. The patient was discharged from the hospital in an improved condition and normal D-Dimer levels. There was no bleeding event nor other major side effects had been found in this case. The decision for increasing dose of anticoagulant may be determined on individual basis, considering risks, benefits, and also the most important is clinical findings.


Assuntos
COVID-19 , Fondaparinux , Hemorragia/prevenção & controle , Embolia Pulmonar , SARS-CoV-2/isolamento & purificação , Trombofilia , Adulto , Antivirais , Azitromicina/administração & dosagem , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , COVID-19/fisiopatologia , Deterioração Clínica , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fondaparinux/administração & dosagem , Fondaparinux/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Inosina Pranobex/administração & dosagem , Lopinavir/administração & dosagem , Masculino , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/etiologia , Trombofilia/complicações , Trombofilia/diagnóstico , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Resultado do Tratamento
6.
Zhonghua Xin Xue Guan Bing Za Zhi ; 49(9): 873-879, 2021 Sep 24.
Artigo em Chinês | MEDLINE | ID: mdl-34530594

RESUMO

Objective: This analysis was performed to evaluate the efficacy and the safety of rivaroxaban-aspirin combination therapy in secondary prevention of major adverse cardiovascular events in Chinese patients enrolled in the COMPASS trial. Methods: COMPASS was a prospective, international multi-center and randomized controlled trial. From September 2014 to February 2017, 1 086 patients with stable coronary artery disease and peripheral artery diseases were recruited from 31 centers in China. Patients were randomly assigned to separately receive the therapy of rivaroxaban (2.5 mg twice a day) plus aspirin (100 mg once a day,) group (n=366), rivaroxaban (5 mg twice a day) alone group (n=365), and aspirin (100 mg once a day) alone group (n=355). Baseline information such as age, sex, etc. of all three groups was collected. Finally, 1 081 patients were followed up successfully, with the follow-up rate 99.5% and the average follow-up time was 19 months. The primary efficacy endpoint was the composite of cardiovascular death, myocardial infarction and stroke. The primary safety endpoint was major bleeding evaluated by modified International Society on Thrombosis and Haemostasis criteria. Results: Age of patients was (64.2±8.3) years and there were 293 male in rivaroxaban plus aspirin group. Age of patients was (63.8±9.0) years, and there were 301 male patients in rivaroxaban alone group. Age of patients was (63.6±8.8) years, and there were 282 male patients in the aspirin alone group. The incidences of primary efficacy endpoint occurred in 9 cases (1.5%) in rivaroxaban with aspirin group, 21 cases (3.7%) in rivaroxaban alone group and 14 cases (2.5%) in aspirin alone group. Meanwhile, the incidences of primary safety endpoint occurred in 6 cases (1.0%) in rivaroxaban with aspirin group, 9 cases (1.6%) in rivaroxaban alone group and 7 cases (1.2%) in aspirin alone group. The net clinical benefit events were 10 cases (1.7%) in rivaroxaban with aspirin group, 22 cases (3.9%) in rivaroxaban alone group and 15 cases (2.7%) in aspirin alone group (P>0.5%). Conclusions: The combination of rivaroxaban with aspirin can be safe and effectively used for the secondary prevention in Chinese patients with stable coronary artery disease and peripheral artery diseases.


Assuntos
Doenças Cardiovasculares , Rivaroxabana , Idoso , Aspirina/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , China , Quimioterapia Combinada , Inibidores do Fator Xa/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos Prospectivos , Rivaroxabana/uso terapêutico , Prevenção Secundária
7.
J Int Med Res ; 49(9): 3000605211047712, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34586928

RESUMO

Although direct-acting oral anticoagulants (DOACs) decrease the bleeding risk compared with vitamin K antagonists (VKAs), DOACs might cause spontaneous hemothorax in very elderly patients, even at a very low dose. Interactions between drugs might increase the risk of bleeding. In this article, we report a case of a 95-year-old man who developed spontaneous hemothorax while taking rivaroxaban 2.5 mg twice daily, 3 days after concomitant use of itraconazole. Rivaroxaban was discontinued, and thoracentesis was performed to drain grossly bloody pleural effusion. To our knowledge, this is the first case report of spontaneous hemothorax that might have been caused by concomitant low-dose rivaroxaban and azole anti-fungal agents. This case highlights the potential risk of spontaneous hemothorax in very elderly patients while taking rivaroxaban and azole anti-fungal agents simultaneously. Special attention should be paid to interactions between drugs that might increase the risk of bleeding. Drugs that have competing metabolic pathways should be avoided. Closer monitoring, including testing for anti-Xa and additional reassessment, should be considered in high-risk patients.


Assuntos
Fibrilação Atrial , Rivaroxabana , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Hemorragia , Hemotórax/tratamento farmacológico , Humanos , Itraconazol/uso terapêutico , Masculino , Rivaroxabana/efeitos adversos
8.
Isr Med Assoc J ; 23(9): 595-600, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34472236

RESUMO

BACKGROUND: Limited data exist regarding the safety of ultrasound-guided femoral nerve blockade (US-FNB) in patients with hip fractures treated with anti-Xa direct oral anticoagulants (DOAC). OBJECTIVES: To compare the safety outcomes of US-FNB to conventional analgesia in patients with hip fractures treated with anti-Xa DOAC. METHODS: This observational exploratory prospective study included 69 patients who presented to our emergency department (ED) in 3 years with hip fracture and who were treated with apixaban or rivaroxaban. Patients received either a US-FNB (n=19) or conventional analgesics (n=50) based on their preference and, and the presence of a trained ED physician qualified in performing US-FNB. Patients were observed for major bleeding events during and 30 days after hospitalization. The degree of preoperative pain and opioid use were also observed. RESULTS: We found no significant difference in the number of major bleeding events between groups (47.4% vs. 54.0%, P = 0.84). Degree of pain measured 3 and 12 hours after presentation was found to be lower in the US-FNB group (median visual analog scale of pain improvement from baseline of -5 vs. -3 (P = 0.002) and -5 vs.-4 (P = 0.023), respectively. Opioid administration pre-surgery was found to be more than three times more common in the conventional analgesia group (26.3% vs.80%, P < 0.0001). CONCLUSIONS: Regarding patients treated with Anti-Xa DOAC, US-FNB was not associated with an increase in major bleeding events compared to conventional analgesia, although it was an effective means of pain alleviation. Larger scale randomized controlled trials are required to determine long-term safety and efficacy.


Assuntos
Inibidores do Fator Xa/administração & dosagem , Fraturas do Quadril/cirurgia , Bloqueio Nervoso/métodos , Dor Pós-Operatória/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Analgésicos/administração & dosagem , Analgésicos Opioides/administração & dosagem , Estudos de Coortes , Serviço Hospitalar de Emergência , Inibidores do Fator Xa/efeitos adversos , Feminino , Nervo Femoral/diagnóstico por imagem , Hemorragia/epidemiologia , Hemorragia/etiologia , Humanos , Masculino , Bloqueio Nervoso/efeitos adversos , Medição da Dor , Projetos Piloto , Estudos Prospectivos , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Ultrassonografia de Intervenção
10.
Cardiovasc Diabetol ; 20(1): 176, 2021 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-34481513

RESUMO

BACKGROUND: It remains uncertain if prior use of oral anticoagulants (OACs) in COVID-19 outpatients with multimorbidity impacts prognosis, especially if cardiometabolic diseases are present. Clinical outcomes 30-days after COVID-19 diagnosis were compared between outpatients with cardiometabolic disease receiving vitamin K antagonist (VKA) or direct-acting OAC (DOAC) therapy at time of COVID-19 diagnosis. METHODS: A study was conducted using TriNetX, a global federated health research network. Adult outpatients with cardiometabolic disease (i.e. diabetes mellitus and any disease of the circulatory system) treated with VKAs or DOACs at time of COVID-19 diagnosis between 20-Jan-2020 and 15-Feb-2021 were included. Propensity score matching (PSM) was used to balance cohorts receiving VKAs and DOACs. The primary outcomes were all-cause mortality, intensive care unit (ICU) admission/mechanical ventilation (MV) necessity, intracranial haemorrhage (ICH)/gastrointestinal bleeding, and the composite of any arterial or venous thrombotic event(s) at 30-days after COVID-19 diagnosis. RESULTS: 2275 patients were included. After PSM, 1270 patients remained in the study (635 on VKAs; 635 on DOACs). VKA-treated patients had similar risks and 30-day event-free survival than patients on DOACs regarding all-cause mortality, ICU admission/MV necessity, and ICH/gastrointestinal bleeding. The risk of any arterial or venous thrombotic event was 43% higher in the VKA cohort (hazard ratio 1.43, 95% confidence interval 1.03-1.98; Log-Rank test p = 0.029). CONCLUSION: In COVID-19 outpatients with cardiometabolic diseases, prior use of DOAC therapy compared to VKA therapy at the time of COVID-19 diagnosis demonstrated lower risk of arterial or venous thrombotic outcomes, without increasing the risk of bleeding.


Assuntos
Assistência Ambulatorial/métodos , Anticoagulantes/administração & dosagem , COVID-19/tratamento farmacológico , Cardiopatias/tratamento farmacológico , Doenças Metabólicas/tratamento farmacológico , Vitamina K/antagonistas & inibidores , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , COVID-19/diagnóstico , COVID-19/mortalidade , Inibidores do Fator Xa/administração & dosagem , Feminino , Seguimentos , Cardiopatias/diagnóstico , Cardiopatias/mortalidade , Hemorragia/induzido quimicamente , Hemorragia/mortalidade , Humanos , Unidades de Terapia Intensiva/tendências , Masculino , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/mortalidade , Pessoa de Meia-Idade , Mortalidade/tendências , Resultado do Tratamento
11.
Int Heart J ; 62(5): 997-1004, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34544976

RESUMO

Catheter ablation for atrial fibrillation (AF) has been an established and frequently utilized approach in a variety of clinical settings. Nevertheless, real-world data about the clinical course of AF patients after initial catheter ablation remain limited, and these are mainly derived from particular registries or selected high-volume centers.In this study, we used health check-ups and insurance claims database from a Japanese insurance organization. The study population was comprised of 1777 patients who underwent catheter ablation for AF before June 2016. During the 3-year follow-up period, 396 (22.3%) patients underwent at least one repeated AF ablation, while 74 (4.2%) underwent two or more repeated ablations. In multivariate Cox regression analysis, longer time after AF diagnosis (7-11 months and ≥12 months versus 1-6 months) (HR, 1.05; 95% CI, 1.01-1.08 and HR, 1.04; 95% CI 1.02-1.07) was independently associated with repeated ablation. The discontinuation rates of OACs and AADs after the first ablation were 26.7% and 63.0% at 3 months and 75.2% and 89.1% at 1 year after the initial ablation, respectively. The former was independently associated with shorter time after AF diagnosis and lower diastolic blood pressure, whereas the latter was independently associated with older age, smaller CHADS2 score, and shorter time after AF diagnosis.We presented real-world data regarding the clinical course of young Japanese AF patients after initial catheter ablation based on a claims database in Japan.


Assuntos
Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Revisão da Utilização de Seguros/estatística & dados numéricos , Adulto , Fatores Etários , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/epidemiologia , Ablação por Cateter/estatística & dados numéricos , Comorbidade , Inibidores do Fator Xa/uso terapêutico , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Análise de Regressão , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
12.
Tohoku J Exp Med ; 255(1): 1-8, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34511578

RESUMO

Endothelial nitric oxide synthase (eNOS) dysfunction is known to exacerbate the progression and prognosis of diabetic kidney disease (DKD). One of the mechanisms through which this is achieved is that low eNOS levels are associated with hypercoagulability, which promotes kidney injury. In the extrinsic coagulation cascade, the tissue factor (factor III) and downstream coagulation factors, such as active factor X (FXa), exacerbate inflammation through activation of the protease-activated receptors (PARs). Recently, it has been shown that the lack of or reduced eNOS expression in diabetic mice, as a model of advanced DKD, increases renal tissue factor levels and PAR1 and 2 expression in their kidneys. Furthermore, pharmaceutical inhibition or genetic deletion of coagulation factors or PARs ameliorated inflammation in DKD in mice lacking eNOS. In this review, we summarize the relationship between eNOS, coagulation, and PARs and propose a novel therapeutic option for the management of patients with DKD.


Assuntos
Nefropatias Diabéticas/etiologia , Óxido Nítrico Sintase Tipo III/deficiência , Receptores Ativados por Proteinase/metabolismo , Animais , Anticorpos Neutralizantes/administração & dosagem , Coagulação Sanguínea , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/fisiopatologia , Modelos Animais de Doenças , Inibidores do Fator Xa/farmacologia , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Camundongos , Camundongos Knockout , Óxido Nítrico Sintase Tipo III/genética , Receptores Ativados por Proteinase/deficiência , Receptores Ativados por Proteinase/genética , Transdução de Sinais , Tromboplastina/antagonistas & inibidores , Tromboplastina/metabolismo
13.
Molecules ; 26(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34500640

RESUMO

Recently, the direct thrombin (thr) inhibitor dabigatran has proven to be beneficial in animal models of Alzheimer's disease (AD). Aiming at discovering novel multimodal agents addressing thr and AD-related targets, a selection of previously and newly synthesized potent thr and factor Xa (fXa) inhibitors were virtually screened by the Multi-fingerprint Similarity Searching aLgorithm (MuSSeL) web server. The N-phenyl-1-(pyridin-4-yl)piperidine-4-carboxamide derivative 1, which has already been experimentally shown to inhibit thr with a Ki value of 6 nM, has been flagged by a new, upcoming release of MuSSeL as a binder of cholinesterase (ChE) isoforms (acetyl- and butyrylcholinesterase, AChE and BChE), as well as thr, fXa, and other enzymes and receptors. Interestingly, the inhibition potency of 1 was predicted by the MuSSeL platform to fall within the low-to-submicromolar range and this was confirmed by experimental Ki values, which were found equal to 0.058 and 6.95 µM for eeAChE and eqBChE, respectively. Thirty analogs of 1 were then assayed as inhibitors of thr, fXa, AChE, and BChE to increase our knowledge of their structure-activity relationships, while the molecular determinants responsible for the multiple activities towards the target enzymes were rationally investigated by molecular cross-docking screening.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/farmacologia , Trombina/metabolismo , Acetilcolinesterase/metabolismo , Doença de Alzheimer/metabolismo , Animais , Butirilcolinesterase/metabolismo , Bovinos , Fator Xa/metabolismo , Inibidores do Fator Xa/farmacologia , Humanos , Simulação de Acoplamento Molecular , Piperidinas/farmacologia , Relação Estrutura-Atividade
14.
Med Klin Intensivmed Notfmed ; 116(6): 491-498, 2021 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-34463792

RESUMO

BACKGROUND: Severe bleeding under antithrombotic therapy is common and challenging in intensive care medicine; on the one hand, rapid bleeding control must be achieved and, on the other hand, thromboembolic complications must be avoided. AIMS: The paper will provide a brief overview of direct oral anticoagulants, therapeutic options and precise instructions for dealing with severe bleeding. RESULTS: In addition to general measures in direct oral anticoagulant (DOAC)-associated major bleeding, prothrombin complex concentrate (PCC), idarucizumab and andexanet alfa are available as specific antidote therapy. In case of bleeding under heparin therapy, protamine sulfate is available as a possible antidote. CONCLUSIONS: In particular, the importance of andexanet alfa in the treatment of factor Xa inhibitor-associated bleeding requires further investigation.


Assuntos
Fibrinolíticos , Hemorragia , Administração Oral , Anticoagulantes/efeitos adversos , Antídotos/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Fibrinolíticos/efeitos adversos , Hemorragia/tratamento farmacológico , Hemorragia/terapia , Humanos , Proteínas Recombinantes/uso terapêutico
16.
Thromb Res ; 206: 99-103, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34454242

RESUMO

BACKGROUND: Anticoagulation therapy, especially using heparin or recently developed oral direct factor Xa inhibitors (DiXals), is recommended as first-line treatment for cancer-related venous thromboembolism (VTE). However, the preventive efficacy of these anticoagulants for cancer-associated ischemic stroke is still unknown. We retrospectively investigated the efficacy of subcutaneous unfractionated heparin (UFH) and DiXals for preventing the recurrence of cancer-associated cryptogenic ischemic stroke with VTE. METHODS: We retrospectively studied consecutive patients with cancer-associated cryptogenic ischemic stroke and comorbid VTE who received subcutaneous UFH or oral DiXaIs at 9 hospitals. RESULT: Fifty-three patients (24 treated with UFH and 29 treated with DiXaIs) were enrolled. Of these, 47 demonstrated systemic metastasis (cancer stage IV). During 30-day follow-up after initiation of anticoagulation therapy, recurrent ischemic stroke was observed in only 1 patient (4%) in the UFH group and in 9 patients (31%) in the DiXal group. The incidence of major bleeding complications was similar between the 2 groups (4% and 10%, respectively). The cumulative risk of ischemic stroke recurrence within 30 days was lower with UFH than with DiXals (competing risk analysis, p = 0.008). In the DiXal group, patients who experienced recurrence showed significantly higher D-dimer levels than those without recurrence. CONCLUSION: In patients with cancer-associated cryptogenic ischemic stroke and comorbid VTE, UFH demonstrated a lower rate of recurrent ischemic stroke than DiXaIs, and there were no differences in bleeding risk between the 2 treatments. D-dimer levels at stroke onset increased the risk of recurrence in the DiXal group but not in the UFH group.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Neoplasias , Acidente Vascular Cerebral , Tromboembolia Venosa , Anticoagulantes/uso terapêutico , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular , Humanos , Neoplasias/complicações , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia
17.
Anesthesiology ; 135(4): 673-685, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34370811

RESUMO

BACKGROUND: Life-threatening bleeding requires prompt reversal of the anticoagulant effects of factor Xa inhibitors. This study investigated the effectiveness of four-factor prothrombin complex concentrate in treating trauma-related hemorrhage with rivaroxaban-anticoagulation in a pig polytrauma model. This study also tested the hypothesis that the combined use of a low dose of prothrombin complex concentrate plus tranexamic acid and fibrinogen concentrate could improve its subtherapeutic effects. METHODS: Trauma (blunt liver injury and bilateral femur fractures) was induced in 48 anesthetized male pigs after 30 min of rivaroxaban infusion (1 mg/kg). Animals in the first part of the study received prothrombin complex concentrate (12.5, 25, and 50 U/kg). In the second part, animals were treated with 12.5 U/kg prothrombin complex concentrate plus tranexamic acid or plus tranexamic acid and fibrinogen concentrate. The primary endpoint was total blood loss postinjury. The secondary endpoints (panel of coagulation parameters and thrombin generation) were monitored for 240 min posttrauma or until death. RESULTS: The first part of the study showed that blood loss was significantly lower in the 25 U/kg prothrombin complex concentrate (1,541 ± 269 ml) and 50 U/kg prothrombin complex concentrate (1,464 ± 108 ml) compared with control (3,313 ± 634 ml), and 12.5 U/kg prothrombin complex concentrate (2,671 ± 334 ml, all P < 0.0001). In the second part of the study, blood loss was significantly less in the 12.5 U/kg prothrombin complex concentrate plus tranexamic acid and fibrinogen concentrate (1,836 ± 556 ml, P < 0.001) compared with 12.5 U/kg prothrombin complex concentrate plus tranexamic acid (2,910 ± 856 ml), and there were no early deaths in the 25 U/kg prothrombin complex concentrate, 50 U/kg prothrombin complex concentrate, and 12.5 U/kg prothrombin complex concentrate plus tranexamic acid and fibrinogen concentrate groups. Histopathologic analyses postmortem showed no adverse events. CONCLUSIONS: Prothrombin complex concentrate effectively reduced blood loss, restored hemostasis, and balanced thrombin generation. A multimodal hemostatic approach using tranexamic acid plus fibrinogen concentrate enhanced the effect of low doses of prothrombin complex concentrate, potentially reducing the prothrombin complex concentrate doses required for effective bleeding control.


Assuntos
Anticoagulantes/toxicidade , Modelos Animais de Doenças , Inibidores do Fator Xa/toxicidade , Hemostasia/efeitos dos fármacos , Traumatismo Múltiplo/tratamento farmacológico , Rivaroxabana/toxicidade , Animais , Fatores de Coagulação Sanguínea/farmacologia , Fatores de Coagulação Sanguínea/uso terapêutico , Terapia Combinada/métodos , Relação Dose-Resposta a Droga , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Hemorragia/fisiopatologia , Hemostasia/fisiologia , Masculino , Traumatismo Múltiplo/induzido quimicamente , Traumatismo Múltiplo/fisiopatologia , Suínos
18.
Expert Rev Clin Pharmacol ; 14(10): 1289-1294, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34402362

RESUMO

PURPOSE: We aimed to investigate the clinical performance of edoxaban for the treatment of pulmonary embolism (PE) in hospitalized COVID-19 patients. METHODS: We conducted a retrospective analysis selecting hospitalized patients with COVID-19 admitted to our Institution from 20 May 2020 to 20 November 2020 with computer tomography (CT) detected PE at admission, treated with edoxaban after initial parenteral therapy. Clinical outcomes were compared between patients with and without ARDS at admission and between those with and without CT confirmed PE resolution. RESULTS: 50 patients were included. Mean follow-up was 42.5 ± 10 days. No baseline differences were found between patients with ARDS (30%) and those without ARDS at admission. Patients with PE resolution (84%) were younger (P = 0.03), had a shorter duration of fondaparinux therapy (9.9 ± 3.8 vs 15.8 ± 7.5 days; P = 0.0015) and length of hospitalization (36 ± 8 vs 46 ± 9 days: P = 0.0023) compared with those without PE resolution. 2 patients experienced major bleedings. At multivariate analysis the time to edoxaban switch was the only predictor of the PE resolution (HR: 0.92; 95% C.I. 0.86 to 0.99). CONCLUSION: Edoxaban was an effective and safe treatment for acute PE in COVID-19 setting.


Assuntos
COVID-19/complicações , Inibidores do Fator Xa/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Piridinas/uso terapêutico , SARS-CoV-2 , Tiazóis/uso terapêutico , Adulto , Idoso , Feminino , Fondaparinux/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Embolia Pulmonar/etiologia , Síndrome do Desconforto Respiratório , Estudos Retrospectivos
19.
Medicine (Baltimore) ; 100(32): e26883, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397907

RESUMO

BACKGROUND AND PURPOSE: This study aimed to evaluate the comparative efficacy and safety of 4 non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in Asians with non-valvular atrial fibrillation in real-world practice through a network meta-analysis of observational studies. METHODS: We searched multiple comprehensive databases (PubMed, Embase, and Cochrane library) for studies published until August 2020. Hazard ratios and 95% confidence intervals were used for the pooled estimates. Efficacy outcomes included ischemic stroke (IS), stroke/systemic embolism (SSE), myocardial infarction (MI), and all-cause mortality, and safety outcomes included major bleeding, gastrointestinal (GI) bleeding, and intracerebral hemorrhage (ICH). The P score was calculated for ranking probabilities. Subgroup analyses were separately performed in accordance with the dosage range of NOACs ("standard-" and "low-dose"). RESULTS: A total of 11, 6, and 8 studies were allocated to the total population, standard-dose group, and low-dose group, respectively. In the total study population, edoxaban ranked the best in terms of IS and ICH prevention and apixaban ranked the best for SSE, major bleeding, and GI bleeding. In the standard-dose regimen, apixaban ranked the best in terms of IS and SSE prevention. For major bleeding, GI bleeding, and ICH, edoxaban ranked the best. In the low-dose regimen, edoxaban ranked the best for IS, SSE, GI bleeding, and ICH prevention. For major bleeding prevention, apixaban ranked best. CONCLUSIONS: All 4 NOACs had different efficacy and safety outcomes according to their type and dosage. Apixaban and edoxaban might be relatively better and more well-balanced treatment for Asian patients with non-valvular atrial fibrillation.


Assuntos
Fibrilação Atrial , Inibidores do Fator Xa , Acidente Vascular Cerebral , Varfarina/farmacologia , Anticoagulantes/farmacologia , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Fibrilação Atrial/etiologia , Fibrilação Atrial/prevenção & controle , Inibidores do Fator Xa/classificação , Inibidores do Fator Xa/farmacologia , Humanos , Avaliação de Resultados em Cuidados de Saúde , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico
20.
Ann Palliat Med ; 10(7): 8082-8093, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34353093

RESUMO

BACKGROUND: To evaluate the efficacy and safety of Xa inhibitors in patients with heart failure (HF) and coronary artery disease (CAD) or peripheral artery disease (PAD). METHODS: A systematic electronic literature search was performed using the PubMed, Web of Science, EMBASE, and Cochrane Library databases from inception to June 26, 2019. A total of four randomized controlled trials involving 14,694 patients were included in this meta-analysis. RESULTS: The meta-analysis showed that there was no statistical difference between the Xa inhibitor and control group regarding the primary efficacy outcome [rivaroxaban 2.5 mg group: relative risk (RR) 0.82, 95% CI: 0.66-1.01, P=0.06; rivaroxaban 5 mg group: RR 0.86, 95% CI: 0.73-1.02, P=0.08]. The risk of the primary safety outcome was significantly increased among patients who received Xa inhibitors compared with the control group (rivaroxaban 2.5 mg group: RR 1.55, 95% CI: 1.21-1.98, P=0.0006; rivaroxaban 5 mg group: RR 1.66, 95% CI: 1.30-2.12, P<0.0001). There was no significant difference in the risk of cardiovascular death between the Xa inhibitor and control group (rivaroxaban 2.5 mg group: RR 0.79, 95% CI: 0.54-1.14, P=0.21; rivaroxaban 5 mg group: RR 0.89, 95% CI: 0.73-1.08, P=0.24). The risk of myocardial infarction (MI) in the rivaroxaban 5 mg group was significantly lower than that of the control group (RR 0.83, 95% CI: 0.69-0.99, P=0.04). However, the risk of MI in the rivaroxaban 2.5 mg group was similar to that of the control group (RR 0.85, 95% CI: 0.71-1.01, P=0.07). DISCUSSION: Xa inhibitors were associated with a higher risk of major adverse cardiovascular events and bleeding among HF and CAD or PAD patients. Therefore, Xa inhibitors should be used cautiously in patients with HF and CAD or PAD.


Assuntos
Insuficiência Cardíaca , Doença Arterial Periférica , Inibidores do Fator Xa/efeitos adversos , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Doença Arterial Periférica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Rivaroxabana/efeitos adversos
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