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1.
Medicine (Baltimore) ; 99(35): e21922, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871929

RESUMO

RATIONALE: Cancer-related stroke has been regarded as an emerging subtype of ischemic event. Acute treatment for this subtype may include the antiplatelet agents, anticoagulants, or endovascular intervention. PATIENT CONCERNS: A 63-year-old woman with sudden-onset right hemiparesis and conscious change was sent to our emergency department. The patient had underlying sigmoid adenocarcinoma and received chemotherapy FOLFIRI (FOL, folinic acid; F, fluorouracil; and IRI, irinotecan) with targeted therapy cetuximab following lower anterior resection since the diagnosis was made. DIAGNOSES: Brain magnetic resonance angiography revealed a filling defect in left carotid bulb, and neurosonography showed a thick atherosclerotic plaque (size 4.9 mm) in the left internal carotid artery on day 5 after the onset of stroke. INTERVENTIONS: During the first three hours after onset, administration of IV tissue plasminogen activator did not resolve the thrombus. Dabigatran (110 mg bid) started on day 7. OUTCOMES: The atherosclerotic plaque dissolved on day 24. The patient recovered her muscle strength but still had nonfluent speech in mild extent. LESSONS: Thrombolytic and anticoagulant medications in this patient suggested the thrombus formation with fibrin-rich content which may be attributable to both cancer and chemotherapy. Dabigatran, an oral anticoagulant, had a benefit for this subtype of ischemic stroke among patients with cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antitrombinas/uso terapêutico , Trombose das Artérias Carótidas/terapia , Artéria Carótida Interna , Infarto da Artéria Cerebral Média/induzido quimicamente , Terapia Trombolítica , Adenocarcinoma/complicações , Adenocarcinoma/tratamento farmacológico , Administração Oral , Trombose das Artérias Carótidas/diagnóstico por imagem , Artéria Carótida Interna/diagnóstico por imagem , Dabigatrana/uso terapêutico , Feminino , Humanos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Angiografia por Ressonância Magnética , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/terapia , Neoplasias do Colo Sigmoide/complicações , Neoplasias do Colo Sigmoide/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico
2.
Trials ; 21(1): 769, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895056

RESUMO

OBJECTIVES: To assess the effect of anticoagulation with bivalirudin administered intravenously on gas-exchange in patients with COVID-19 and respiratory failure using invasive mechanical ventilation. TRIAL DESIGN: This is a single centre parallel group, superiority, randomized (1:1 allocation ratio) controlled trial. PARTICIPANTS: All patients admitted to the Hamad Medical Corporation -ICU in Qatar for COVID-19 associated respiratory distress and in need of mechanical ventilation are screened for eligibility. INCLUSION CRITERIA: all adult patients admitted to the ICU who test positive for COVID-19 by PCR-test and in need for mechanical ventilation are eligible for inclusion. Upon crossing the limit of D-dimers (1.2 mg/L) these patients are routinely treated with an increased dose of anticoagulant according to our local protocol. This will be the start of randomization. EXCLUSION CRITERIA: pregnancy, allergic to the drug, inherited coagulation abnormalities, no informed consent. INTERVENTION AND COMPARATOR: The intervention group will receive the anticoagulant bivalirudin intravenously with a target aPTT of 45-70 sec for three days while the control group will stay on the standard treatment with low-molecular-weight heparins /unfractionated heparin subcutaneously (see scheme in Additional file 1). All other treatment will be unchanged and left to the attending physicians. MAIN OUTCOMES: As a surrogate parameter for clinical improvement and primary outcome we will use the PaO2/FiO2 (P/F) ratio. RANDOMISATION: After inclusion, the patients will be randomized using a closed envelope method into the conventional treatment group, which uses the standard strategy and the experimental group which receives anticoagulation treatment with bivalirudin using an allocation ratio of 1:1. BLINDING (MASKING): Due to logistical and safety reasons (assessment of aPTT to titrate the study drug) only the data-analyst will be blinded to the groups. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): We performed a sample size calculation and assumed the data for P/F ratio (according to literature) is normally distributed and used the mean which would be: 160 and SD is 80. We expect the treatment will improve this by 30%. In order to reach a power of 80% we would need 44 patients per group (in total 88 patients). Taking approximately 10% of dropout into account we will include 100 patients (50 in each group). TRIAL STATUS: The local registration number is MRC-05-082 with the protocol version number 2. The date of approval is 18th June 2020. Recruitment started on 28th June and is expected to end in November 2020. TRIAL REGISTRATION: The protocol is registered before starting subject recruitment under the title: "Anticoagulation in patients suffering from COVID-19 disease. The ANTI-CO Trial" in ClinicalTrials.org with the registration number: NCT04445935 . Registered on 24 June 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 2). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Antitrombinas/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Fragmentos de Peptídeos/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Respiração Artificial , Síndrome do Desconforto Respiratório do Adulto/terapia , Anticoagulantes/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/sangue , Estado Terminal , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Hirudinas , Humanos , Pandemias , Tempo de Tromboplastina Parcial , Pneumonia Viral/sangue , Catar , Proteínas Recombinantes/uso terapêutico
3.
Medicine (Baltimore) ; 99(33): e21681, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872038

RESUMO

The aging of the population has resulted in atrial fibrillation (AF) becoming increasingly prevalent. Treatment focuses on the prevention of thromboembolism through the use of catheter ablation or drug therapy with anticoagulants, such as warfarin or direct oral anticoagulants (DOACs). Dabigatran-induced exfoliative esophagitis has been reported as a rare side effect of DOACs. Although most cases are mild, some result in severe outcomes. However, the etiology of exfoliative esophagitis remains incompletely understood. The aim of this study is to investigate the etiology of exfoliative esophagitis and identify its risk factors by observational study.The participants were 524 patients using anticoagulants who received catheter ablation for AF and subsequently underwent upper gastrointestinal endoscopy at University of Tsukuba Hospital. Exfoliative esophagitis was noted in 21 (4.0%) patients. Potential risk factors for exfoliative esophagitis were examined retrospectively by comparing patients with and without this condition across the following parameters that were extracted retrospectively from the electronic medical records: physical characteristics, comorbidities, blood-based cardiac markers, echocardiographic and endoscopic findings, and current medications.Regarding physical characteristics, patients with exfoliative esophagitis had significantly higher body weight and BMI. No association was observed between exfoliative esophagitis and comorbidities. Associations were also not found for cardiac markers, echocardiographic findings, or endoscopic findings. In terms of current medications, patients receiving oral dabigatran showed the highest prevalence of exfoliative esophagitis at 8.8% (13/148). The adjusted odds ratio of dabigatran for exfoliative esophagitis was 10.3 by multivariable logistic regression analysis.Obesity and oral dabigatran were found to be significant risk factors for exfoliative esophagitis.


Assuntos
Antitrombinas/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/efeitos adversos , Esofagite/induzido quimicamente , Idoso , Fibrilação Atrial/complicações , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Estudos Retrospectivos , Fatores de Risco
5.
Khirurgiia (Mosk) ; (7): 68-75, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32736466

RESUMO

The paper is a narrative review of the literature on the use of direct oral anticoagulants (DOACs) for the VTE treatment in challenging patients: senile age (≥75 years), impaired renal function (estimated glomerular filtration rate ≤50 ml/min), fragility (one of the previous characteristics and/or bodyweight ≤50 kg). The paper discusses the studies of EINSTEIN DVT and PE (rivaroxaban), AMPLIFY (apixaban), HOKUSAI-VTE (edoxaban), RE-COVER I and II (dabigatran) in the focus of the secondary analysis in the pre-specified patient's subgroups, as well as their pooled analyzes and meta-analyzes. Based on the results of this review, it was concluded that in a subgroup of senile age patients, dabigatran increases the risk of major bleeding by 4.8 times and has no advantages over vitamin K antagonists (VKA); rivaroxaban and apixaban retain superiority over VKA on the safety outcomes and reduce the risk of major bleeding by 73% and 77%. In the subgroup of patients with impaired renal function, the use of apixaban and dabigatran is associated with an increase in the risk of major bleeding by 6.5 and 7.3 times, and these DOACs do not have advantages over VKA; rivaroxaban retains its superiority over VKA and reduces the risk of major bleeding by 78%. For fragile patients, a secondary analysis is available only for rivaroxaban, which remains superior to VKA on safety endpoints and reduces the risk of major bleeding by 73%. In the absence of direct comparisons between the available DOACs, the presented data can be used as a rational approach for the choice of appropriate treatment for VTE in challenging patients.


Assuntos
Dabigatrana/efeitos adversos , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Insuficiência Renal/complicações , Rivaroxabana/efeitos adversos , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Fatores Etários , Idoso , Antitrombinas , Dabigatrana/administração & dosagem , Idoso Fragilizado , Humanos , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Rivaroxabana/administração & dosagem , Tromboembolia Venosa/complicações
6.
Paediatr Respir Rev ; 35: 20-24, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32653469

RESUMO

Since the initial description in 2019, the novel coronavirus SARS-Cov-2 infection (COVID-19) pandemic has swept the globe. The most severe form of the disease presents with fever and shortness of breath, which rapidly deteriorates to respiratory failure and acute lung injury (ALI). COVID-19 also presents with a severe coagulopathy with a high rate of venous thromboembiolism. In addition, autopsy studies have revealed co-localized thrombosis and inflammation, which is the signature of thromboinflammation, within the pulmonary capillary vasculature. While the majority of published data is on adult patients, there are parallels to pediatric patients. In our experience as a COVID-19 epicenter, children and young adults do develop both the coagulopathy and the ALI of COVID-19. This review will discuss COVID-19 ALI from a hematological perspective with discussion of the distinct aspects of coagulation that are apparent in COVID-19. Current and potential interventions targeting the multiple thromboinflammatory mechanisms will be discussed.


Assuntos
Lesão Pulmonar Aguda/sangue , Infecções por Coronavirus/sangue , Inflamação/sangue , Pneumonia Viral/sangue , Trombose/sangue , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/fisiopatologia , Anticoagulantes/uso terapêutico , Antitrombinas/uso terapêutico , Betacoronavirus , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/imunologia , Transtornos da Coagulação Sanguínea/fisiopatologia , Capilares/imunologia , Capilares/fisiopatologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Endotélio Vascular/imunologia , Endotélio Vascular/fisiopatologia , Inibidores do Fator Xa/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/fisiopatologia , Pandemias , Ativação Plaquetária , Inibidores da Agregação de Plaquetas/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Embolia Pulmonar/sangue , Embolia Pulmonar/imunologia , Embolia Pulmonar/fisiopatologia , Trombina/imunologia , Trombina/metabolismo , Trombose/tratamento farmacológico , Trombose/imunologia , Trombose/fisiopatologia
7.
PLoS One ; 15(7): e0235511, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32645042

RESUMO

BACKGROUND: There is recent new evidence regarding the combined use of direct oral antiocoagulants and antiplatelet agents in patients with Atrial Fibrillation undergoing PCI. PURPOSE: To compare the efficacy of dual antithrombotic treatment (DAT) including a direct oral anticoagulant (DOAC) and an antiplatelet agent versus triple antithrombotic treatment (TAT) with a vitamin K antagonist (VKA). DATA SOURCES: PubMed, SCOPUS and Google Scholar from through 09/09/2019; references of eligible studies; relevant scientific sessions abstracts and cardiology websites. STUDY SELECTION: Randomized controlled trials that compared DAT including a DOAC with TAT including a VKA and that reported at least the rates of stroke, Stent thrombosis and bleeding. DATA EXTRACTION: Two investigators independently extracted study data and assessed study quality. DATA SYNTHESIS: Four randomized trials that compared DAT including a DOAC with TAT including a VKA were available. Among these, one trial included two independent treatment arms with different DOAC dose, both compared against TAT. For this reason, the two arms were treated independently, resulting in 5 randomized comparisons available for meta-analysis, with a total of 8654 patients involved. The primary safety endpoint was significantly lower in the DAT arm (14.4%) compared to the TAT arm (23%) (RD = -0.08; p<0.001). In addition, we found no significant difference in the incidence of stroke between the treatment arms (p = 0.23). Similarly, no significant difference in the incidence of Stent Thrombosis between the treatment arms (p = 0.08). LIMITATIONS: All trials included were open-label, even though data were blindly analyzed. Qualifying criteria are heterogeneous. CONCLUSIONS: Compared TAT including a VKA, a therapeutic DAT regimen including a DOAC was associated with a significant reduction of the primary safety endpoint in AF patients undergoing PCI with stent implantation for an ACS or chronic coronary syndrome, while no significant difference was found in the rate of ischemic adverse events, including stroke, acute myocardial infarction or stent thrombosis.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Antitrombinas/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/uso terapêutico , Síndrome Coronariana Aguda/cirurgia , Antitrombinas/administração & dosagem , Antitrombinas/efeitos adversos , Fibrilação Atrial/cirurgia , Ensaios Clínicos como Assunto , Combinação de Medicamentos , Humanos , Inibidores da Agregação de Plaquetas/administração & dosagem
8.
Am J Cardiol ; 128: 120-126, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32650905

RESUMO

Women and patients with incomplete revascularization (IR) have a worse prognosis after ST elevation myocardial infarction (STEMI). However, the extent to which IR affects outcomes for women with STEMI compared with men is not well characterized. Thus, we examined late outcomes of 589 consecutive STEMI patients who received percutaneous coronary intervention and assessed SYNTAX scores (SS), both at baseline and after all procedures (residual SS). A residual SS >8 defined IR. The primary end point was cardiac death or myocardial infarction (MI), with median follow-up of 3.6 years [interquartile range [IQR] 2.6 to 4.7]. Women (n = 123) had lower baseline SSs 15.0 [IQR 9 to 20], than men (n = 466), 16.0 [IQR 9 to 20; p = 0.02. After all planned procedures, the residual SS was 5.0 [IQR 0 to 9] in women and 5.0 (IQR 1 to 11] in men, p = 0.37. Cardiac death or MI occurred in (97/589) patients (16%), 24% (30/123) in women and 14% (67/466) in men (hazard ratio [HR] 1.75; 95% confidence intervals [CI] 1.14 to 2.69; p = 0.01). In patients with residual SYNTAX score (rSS) >8 cardiac death or MI occurred in 43% (15/35) of women and 23% 36/158 men (HR 2.14; 95% CI 1.17 to 3.91; p = 0.01). In patients with rSS = 0 to 8 cardiac death or MI occurred in 17% (15/88) of women and 10% of men (31/308) (HR 1.68; 95% CI 0.91 to 3.12; p = 0.10; interaction p value 0.58). Multivariate analysis found women were 1.77 times more likely than men to experience cardiac death or MI (95% CI 1.13 to 2.77; p = 0.01). In conclusion, we found despite a lower burden of disease at presentation and no difference in rates of IR between men and women, outcome differences were substantial. Women with rSS >8 were twice as likely as men with the same rSS to experience cardiac death or MI post-STEMI. Differences remained significant postrisk adjustment.


Assuntos
Cardiopatias/mortalidade , Infarto do Miocárdio/epidemiologia , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Terapia Trombolítica , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antitrombinas/uso terapêutico , Feminino , Seguimentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Modelos de Riscos Proporcionais , Recidiva , Fatores Sexuais , Stents , Resultado do Tratamento
9.
Medicine (Baltimore) ; 99(27): e20533, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629634

RESUMO

BACKGROUND: This study aims to check the effect of hirudin on serum matrix metalloproteinase-9 (SMMP9) in patients with acute cerebral infarction (ACI). METHODS: For acquisition of obtained data of included studies, we will undertake comprehensive search from the following electronic databases: MEDLINE, Embase, Cochrane Library, CINAHL, WANGFANG database, VIP database, CBM database, and China National Knowledge Infrastructure from their inceptions to the March 31, 2020. No restrictions of language and publication status will be applied to all database sources. Two investigators will independently undertake study selection, data extraction, and study quality. Any different opinions between 2 investigators will be solved by a third investigator through consultation. Study quality will be assessed using Cochrane risk of bias tool, and level of evidence for outcome results will be identified using the Grading of Recommendations Assessment, Development, and Evaluation method. We will use RevMan 5.3 software for statistical analysis. RESULTS: From this study, we will evaluate the effect of hirudin on SMMP9 in patients with ACI. CONCLUSION: The findings of this study will provide evidence to ensure the effect of hirudin on SMMP9 in patients with ACI.


Assuntos
Antitrombinas/uso terapêutico , Infarto Cerebral/tratamento farmacológico , Terapia com Hirudina , Metaloproteinase 9 da Matriz/sangue , Infarto Cerebral/sangue , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
10.
Medicine (Baltimore) ; 99(27): e21025, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629725

RESUMO

BACKGROUND: Given the huge burden of atrial fibrillation (AF) and AF-related stroke in Asia, stroke prevention represents an urgent issue in this region. We herein performed a network meta-analysis to examine the role of non-vitamin K antagonist oral anticoagulants (NOACs) in Asian patients with AF. METHODS: A systematic search of the publications was conducted in PubMed and Embase databases for eligible studies until July 2019. The odds ratios (ORs) and 95% confidence intervals (CIs) were regarded as the effect estimates. The surface under the cumulative ranking area (SUCRA) for the ranking probabilities was calculated. RESULTS: A total of 17 studies were included. For comparisons of NOACs vs warfarin, dabigatran (OR = 0.77, 95% CI 0.68-0.86), rivaroxaban (OR = 0.72, 95% CI 0.65-0.81), apixaban (OR = 0.56, 95% CI 0.49-0.65), but not edoxaban reduced the risk of stroke or systemic embolism, wheres dabigatran (OR = 0.56, 95% CI 0.41-0.76), rivaroxaban (OR = 0.66, 95% CI 0.50-0.86), apixaban (OR = 0.49, 95% CI 0.36-0.66), and edoxaban (OR = 0.34, 95% CI 0.24-0.49) decreased the risk of major bleeding. In reducing the risk of stroke or systemic embolism, apixaban and rivaroxaban ranked the best and second best (SUCRA 0.2% and 31.4%, respectively), followed by dabigatran (50.2%), edoxaban (75.2%), and warfarin (93.0%). In reducing the risk of major bleeding, edoxaban, and apixaban ranked the best and second best (1.5% and 30.8%, respectively), followed by dabigatran (48.4%), rivaroxaban (69.2%), and warfarin (100%). CONCLUSION: NOACs were at least as effective as warfarin, but more safer in Asians with AF. Apixaban was superior to other NOACs for reducing stroke or systemic embolism, while edoxaban showed a better safety profile than other NOACs.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Varfarina/uso terapêutico , Administração Oral , Idoso , Antitrombinas/uso terapêutico , Ásia/epidemiologia , Grupo com Ancestrais do Continente Asiático/etnologia , Efeitos Psicossociais da Doença , Dabigatrana/uso terapêutico , Embolia/prevenção & controle , Inibidores do Fator Xa/uso terapêutico , Feminino , Hemorragia/prevenção & controle , Humanos , Masculino , Metanálise em Rede , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Segurança , Acidente Vascular Cerebral/epidemiologia , Tiazóis/uso terapêutico
12.
A A Pract ; 14(7): e01236, 2020 May.
Artigo em Inglês | MEDLINE | ID: covidwho-601387

RESUMO

Critically ill patients with coronavirus disease 2019 (COVID-19) have been observed to be hypercoagulable, but the mechanisms for this remain poorly described. Factor VIII is a procoagulant factor that increases during inflammation and is cleaved by activated protein C. To our knowledge, there is only 1 prior study of factor VIII and functional protein C activity in critically ill patients with COVID-19. Here, we present a case series of 10 critically ill patients with COVID-19 who had severe elevations in factor VIII activity and low normal functional protein C activity, which may have contributed to hypercoagulability.


Assuntos
Infecções por Coronavirus/sangue , Fator VIII/metabolismo , Pneumonia Viral/sangue , Proteína C/metabolismo , Síndrome do Desconforto Respiratório do Adulto/sangue , Trombofilia/sangue , Lesão Renal Aguda/epidemiologia , Lesão Renal Aguda/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antitrombinas/metabolismo , Betacoronavirus , Proteína C-Reativa/metabolismo , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Estado Terminal , Diabetes Mellitus/epidemiologia , Dislipidemias/epidemiologia , Oxigenação por Membrana Extracorpórea , Feminino , Ferritinas/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Humanos , Hipertensão/epidemiologia , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Pandemias , Tempo de Tromboplastina Parcial , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Tempo de Protrombina , Diálise Renal , Insuficiência Renal Crônica/epidemiologia , Respiração Artificial , Síndrome do Desconforto Respiratório do Adulto/epidemiologia , Síndrome do Desconforto Respiratório do Adulto/terapia
13.
A A Pract ; 14(7): e01236, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32539272

RESUMO

Critically ill patients with coronavirus disease 2019 (COVID-19) have been observed to be hypercoagulable, but the mechanisms for this remain poorly described. Factor VIII is a procoagulant factor that increases during inflammation and is cleaved by activated protein C. To our knowledge, there is only 1 prior study of factor VIII and functional protein C activity in critically ill patients with COVID-19. Here, we present a case series of 10 critically ill patients with COVID-19 who had severe elevations in factor VIII activity and low normal functional protein C activity, which may have contributed to hypercoagulability.


Assuntos
Infecções por Coronavirus/sangue , Fator VIII/metabolismo , Pneumonia Viral/sangue , Proteína C/metabolismo , Síndrome do Desconforto Respiratório do Adulto/sangue , Trombofilia/sangue , Lesão Renal Aguda/epidemiologia , Lesão Renal Aguda/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antitrombinas/metabolismo , Betacoronavirus , Proteína C-Reativa/metabolismo , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Estado Terminal , Diabetes Mellitus/epidemiologia , Dislipidemias/epidemiologia , Oxigenação por Membrana Extracorpórea , Feminino , Ferritinas/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Humanos , Hipertensão/epidemiologia , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Pandemias , Tempo de Tromboplastina Parcial , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Tempo de Protrombina , Diálise Renal , Insuficiência Renal Crônica/epidemiologia , Respiração Artificial , Síndrome do Desconforto Respiratório do Adulto/epidemiologia , Síndrome do Desconforto Respiratório do Adulto/terapia
14.
Am Heart J ; 225: 38-43, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32485328

RESUMO

BACKGROUND: Previous studies have implied the efficacy and safety of argatroban plus recombinant tissue-type plasminogen activator (r-tPA) in patients with acute ischemic stroke. Further trials are needed to establish convincing conclusions in a large sample size. RESEARCH DESIGN AND METHODS: Argatroban plus r-tPA for Acute Ischemic Stroke (ARAIS) trial is a multicenter, prospective, randomized, open-label, and blind-end point trial. The trial proposes to randomize 808 patients with acute ischemic stroke National Institutes of Health Stroke Scale (NIHSS score≥ 6 at the time of randomization) within 4.5 hours of symptom onset to receive argatroban (100 µg/kg bolus followed by an infusion of 1.0 µg/kg per minute for 48 hours) plus r-tPA or r-tPA alone. The primary end point is the proportion of patients with an excellent outcome of no clinically significant residual stroke deficits (modified Rankin scale 0-1) at 90 days. Secondary end points include the proportion of patients with a good outcome (modified Rankin scale 0-2) at 90 days, early neurological improvement (NIHSS score ≥2-point decrease) at 48 hours, early neurological deterioration (NIHSS score ≥4-point increase) at 48 hours, decrease in the NIHSS score from baseline to 14 days, and stroke recurrence or other vascular events at 90 days. Safety end points include symptomatic intracerebral hemorrhage, parenchymal hematoma type 2, and major systemic bleeding. CONCLUSION: ARAIS trial will evaluate whether argatroban plus r-tPA is superior to r-tPA alone in improving functional outcomes in acute ischemic stroke patients in a large sample population.


Assuntos
Antitrombinas/uso terapêutico , Ácidos Pipecólicos/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Adulto Jovem
15.
Medicine (Baltimore) ; 99(21): e20200, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481289

RESUMO

RATIONALE: Idarucizumab is a specific reversal agent for patients with bleeding related to the anticoagulant dabigatran. There are no prior descriptions of Idarucizumab administration in the prehospital setting for intracranial hemorrhage. PATIENT CONCERNS: An 82-year-old woman treated with dabigatran for atrial fibrillation developed acute focal weakness. This led to activation of emergency medical services and assessment in the mobile stroke unit (MSU). DIAGNOSIS: Computed tomography of the brain performed in the MSU revealed an acute subdural hematoma. INTERVENTIONS: The patient was treated with Idarucizumab in the MSU. OUTCOMES: The subdural hematoma was treated with a burr hole evacuation and the patient was discharged to a rehabilitation facility without residual focal neurological deficits. LESSONS: Idarucizumab can be used safely and effectively to treat dabigatran-associated intracranial hemorrhage in the prehospital setting.


Assuntos
Antitrombinas/efeitos adversos , Dabigatrana/efeitos adversos , Hematoma Subdural/induzido quimicamente , Hematoma Subdural/tratamento farmacológico , Administração Intravenosa , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Antitrombinas/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/uso terapêutico , Serviços Médicos de Emergência , Feminino , Hematoma Subdural/diagnóstico por imagem , Hematoma Subdural/cirurgia , Humanos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Trepanação/métodos
18.
Am J Hematol ; 95(7): 863-869, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32350907

RESUMO

Ecarin is derived from venom of Echis carinatus, and will activate prothrombin into meizothrombin which will then cleave fibrinogen to result in clot formation. Ecarin based testing has been described for decades, but these assays were typically restricted to reference or speciality coagulation laboratories. This test was initially described for the assessment of direct thrombin inhibitors (eg, bivalirudin lepirudin, or argatroban) and was not affected by heparins or heparinoids. Ecarin based assays were rarely used for anticoagulation monitoring until the emergence of the direct oral thrombin inhibitor dabigatran etexilate in 2010. As this test was mentioned in the prescribing information for dabigatran etexilate, there was increased interest for use by clinical laboratories as the preferred method for assessing the anticoagulant effect of this drug. The purpose of this document is to review the current status of ecarin based assays for assessing dabigatran. This is with the understanding that these methods can also be exploited for determining the anticoagulation effect of parenteral direct thrombin inhibitors, such as argatroban and bivalirudin.


Assuntos
Antitrombinas/farmacocinética , Dabigatrana/farmacocinética , Monitoramento de Medicamentos , Endopeptidases/química , Antitrombinas/uso terapêutico , Testes de Coagulação Sanguínea , Dabigatrana/uso terapêutico , Humanos
19.
Cardiovasc Ther ; 2020: 9783630, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32405324

RESUMO

Introduction: Anticoagulants such as argatroban and heparins (low-molecular-weight and unfractionated) play an immense role in preventing thromboembolic complications in clinical practice. Nevertheless, they can also have a negative effect on the immune system. This study is aimed at investigating the influence of these substances on polymorphonuclear neutrophils (PMNs), whose nonspecific defense mechanisms can promote thrombogenesis. Methods: Blood samples from 30 healthy volunteers were investigated, whereby PMNs were isolated by density gradient centrifugation and incubated with 0.8 µg/mL of argatroban, 1.0 U/mL of low-molecular-weight heparin (LMWH), 1.0 U/mL of unfractionated heparin (UFH), or without drug (control). A collagen-cell mixture was prepared and filled into 3D µ-slide chemotaxis chambers (IBIDI® GmbH, Germany). Stimulation was initiated by using a chemokine gradient of n-formyl-methionine-leucyl-phenylalanine (fMLP), and microscopic observation was conducted for 4.5 hours. The cells' track length and track straightness, as well as the number of attracted granulocytes, level of ROS (reactive oxygen species) production, and NET (neutrophil extracellular traps) formation, were analyzed and categorized into migration distances and time periods. Results: All three anticoagulants led to significantly reduced PMN track lengths, with UFH having the biggest impact. The number of tracks observed in the UFH group were significantly reduced compared to the control group. Additionally, the UFH group demonstrated a significantly lower track straightness compared to the control. ROS production and NET formation were unaffected. Conclusion: Our data provide evidence that anticoagulants have an inhibitory effect on the extent of PMN migration and chemotactic migration efficiency, thus indicating their potential immune-modulatory and prothrombotic effects.


Assuntos
Anticoagulantes/efeitos adversos , Antitrombinas/efeitos adversos , Quimiotaxia de Leucócito/efeitos dos fármacos , Enoxaparina/efeitos adversos , Granulócitos/efeitos dos fármacos , Ácidos Pipecólicos/efeitos adversos , Adulto , Armadilhas Extracelulares/metabolismo , Feminino , Granulócitos/imunologia , Granulócitos/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Espécies Reativas de Oxigênio/metabolismo , Adulto Jovem
20.
J Thromb Haemost ; 18(6): 1320-1323, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: covidwho-116313

RESUMO

BACKGROUND: Antiviral drugs are administered in patients with severe COVID-19 respiratory syndrome, including those treated with direct oral anticoagulants (DOACs). Concomitant administration of antiviral agents has the potential to increase their plasma concentration. A series of patients managed in the Cremona Thrombosis Center were admitted at Cremona Hospital for SARS-CoV-2 and started antiviral drugs without stopping DOAC therapy. DOAC plasma levels were measured in hospital and results compared with those recorded before hospitalization. METHODS: All consecutive patients on DOACs were candidates for administration of antiviral agents (lopinavir, ritonavir, or darunavir). Plasma samples for DOAC measurement were collected 2to 4 days after starting antiviral treatment, at 12 hours from the last dose intake in patients on dabigatran and apixaban, and at 24 hours in those on rivaroxaban and edoxaban. For each patient, C-trough DOAC level, expressed as ng/mL, was compared with the one measured before hospitalization. RESULTS: Of the 1039 patients hospitalized between February 22 and March 15, 2020 with COVID-19 pneumonia and candidates for antiviral therapy, 32 were on treatment with a DOAC. DOAC was stopped in 20 and continued in the remaining 12. On average, C-trough levels were 6.14 times higher during hospitalization than in the pre-hospitalization period. CONCLUSION: DOAC patients treated with antiviral drugs show an alarming increase in DOAC plasma levels. In order to prevent bleeding complications, we believe that physicians should consider withholding DOACs from patients with SARS-CoV-2 and replacing them with alternative parenteral antithrombotic strategies for as long as antiviral agents are deemed necessary and until discharge.


Assuntos
Antitrombinas/sangue , Antivirais/efeitos adversos , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Dabigatrana/sangue , Inibidores do Fator Xa/sangue , Pneumonia Viral/tratamento farmacológico , Pirazóis/sangue , Piridinas/sangue , Piridonas/sangue , Tiazóis/sangue , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Antitrombinas/administração & dosagem , Antitrombinas/efeitos adversos , Antivirais/administração & dosagem , Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Dabigatrana/administração & dosagem , Dabigatrana/efeitos adversos , Darunavir/efeitos adversos , Interações Medicamentosas , Monitoramento de Medicamentos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Itália , Lopinavir/efeitos adversos , Masculino , Pandemias , Segurança do Paciente , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Medição de Risco , Fatores de Risco , Ritonavir/efeitos adversos , Índice de Gravidade de Doença , Tiazóis/administração & dosagem , Tiazóis/efeitos adversos
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