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1.
N Engl J Med ; 385(7): 609-617, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34297496

RESUMO

BACKGROUND: The role of factor XI in the pathogenesis of postoperative venous thromboembolism is uncertain. Abelacimab is a monoclonal antibody that binds to factor XI and locks it in the zymogen (inactive precursor) conformation. METHODS: In this open-label, parallel-group trial, we randomly assigned 412 patients who were undergoing total knee arthroplasty to receive one of three regimens of abelacimab (30 mg, 75 mg, or 150 mg) administered postoperatively in a single intravenous dose or to receive 40 mg of enoxaparin administered subcutaneously once daily. The primary efficacy outcome was venous thromboembolism, detected by mandatory venography of the leg involved in the operation or objective confirmation of symptomatic events. The principal safety outcome was a composite of major or clinically relevant nonmajor bleeding up to 30 days after surgery. RESULTS: Venous thromboembolism occurred in 13 of 102 patients (13%) in the 30-mg abelacimab group, 5 of 99 patients (5%) in the 75-mg abelacimab group, and 4 of 98 patients (4%) in the 150-mg abelacimab group, as compared with 22 of 101 patients (22%) in the enoxaparin group. The 30-mg abelacimab regimen was noninferior to enoxaparin, and the 75-mg and 150-mg abelacimab regimens were superior to enoxaparin (P<0.001). Bleeding occurred in 2%, 2%, and none of the patients in the 30-mg, 75-mg, and 150-mg abelacimab groups, respectively, and in none of the patients in the enoxaparin group. CONCLUSIONS: This trial showed that factor XI is important for the development of postoperative venous thromboembolism. Factor XI inhibition with a single intravenous dose of abelacimab after total knee arthroplasty was effective for the prevention of venous thromboembolism and was associated with a low risk of bleeding. (Funded by Anthos Therapeutics; ANT-005 TKA EudraCT number, 2019-003756-37.).


Assuntos
Anticoagulantes/uso terapêutico , Artroplastia do Joelho , Enoxaparina/uso terapêutico , Fator XI/antagonistas & inibidores , Complicações Pós-Operatórias/prevenção & controle , Tromboembolia Venosa/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Relação Dose-Resposta a Droga , Enoxaparina/efeitos adversos , Fator XI/metabolismo , Feminino , Hemorragia/induzido quimicamente , Humanos , Infusões Intravenosas , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial
2.
Thromb Res ; 205: 120-127, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34311154

RESUMO

BACKGROUND: In intensive-care unit (ICU) patients, pathophysiological changes may affect the pharmacokinetics of enoxaparin and result in underdosing. OBJECTIVES: To develop a pharmacokinetic model of enoxaparin to predict the time-exposure profiles of various thromboprophylactic regimens in COVID-19 ICU-patients. METHODS: This was a retrospective study in ICUs of two French hospitals. Anti-Xa activities from consecutive patients with laboratory-confirmed SARS-CoV-2 infection treated with enoxaparin for the prevention or the treatment of venous thrombosis were used to develop a population pharmacokinetic model using non-linear mixed effects techniques. Monte Carlo simulations were then performed to predict enoxaparin exposure at steady-state after three days of administration. RESULTS: A total of 391 anti-Xa samples were measured in 95 patients. A one-compartment model with first-order kinetics best fitted the data. The covariate analysis showed that enoxaparin clearance (typical value 1.1 L.h-1) was related to renal function estimated by the CKD-EPI formula and volume of distribution (typical value 17.9 L) to actual body weight. Simulation of anti-Xa activities with enoxaparin 40 mg qd indicated that 64% of the patients had peak levels within the range 0.2 to 0.5 IU.mL-1 and 75% had 12-hour levels above 0.1 IU.mL-1. Administration of a total daily dose of at least 60 mg per day improved the probability of target attainment. CONCLUSION: In ICU COVID-19 patients, exposure to enoxaparin is reduced due to an increase in the volume of distribution and clearance. Consequently, enoxaparin 40 mg qd is suboptimal to attain thromboprophylactic anti-Xa levels.


Assuntos
COVID-19 , Enoxaparina , Anticoagulantes , Estado Terminal , Enoxaparina/uso terapêutico , Humanos , Estudos Retrospectivos , SARS-CoV-2
3.
Clin Drug Investig ; 41(8): 723-732, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34328635

RESUMO

BACKGROUND AND OBJECTIVE: Low-dose acetylsalicylic acid (ASA, aspirin) is a well-known and frequently studied drug for primary and secondary prevention of disease due to its anti-inflammatory and coagulopathic effects. COVID-19 complications are attributed to the role of thrombo-inflammation. Studies regarding the use of low-dose ASA in COVID-19 are limited. For this reason, we propose that the use of low-dose ASA may have protective effects in COVID-19-related thromboembolism and lung injury. This study was conducted to assess the efficacy of low-dose ASA compared with enoxaparin, an anticoagulant, for the prevention of thrombosis and mechanical ventilation. METHODS: We conducted a retrospective cohort study on COVID-19-confirmed hospitalized patients at the Mansoura University Quarantine Hospital, outpatients, and home-isolated patients from September to December 2020 in Mansoura governorate, Egypt. Binary logistic regression analysis was used to assess the effect of ASA compared with enoxaparin on thromboembolism, and mechanical ventilation needs. RESULTS: This study included 225 COVID-19 patients. Use of ASA-only (81-162 mg orally daily) was significantly associated with reduced thromboembolism (OR 0.163, p = 0.020), but both low-dose ASA and enoxaparin, and enoxaparin-only (0.5 mg/kg subcutaneously (SC) daily as prophylactic dose or 1 mg/kg SC every 12 hours as therapeutic dose) were more protective (odds ratio [OR] 0.010, OR 0.071, respectively, p < 0.001). Neither ASA-only nor enoxaparin-only were associated with a reduction in mechanical ventilation needs. Concomitant use of low-dose ASA and enoxaparin was associated with reduced mechanical ventilation (OR 0.032, 95% CI 0.004-0.226, p = 0.001). CONCLUSIONS: Low-dose ASA-only use may reduce the incidence of COVID-19-associated thromboembolism, but the reduction may be less than that of enoxaparin-only, and both ASA and enoxaparin. Concomitant use of ASA and enoxaparin demonstrates promising results with regard to the reduction of thrombotic events, and mechanical ventilation needs.


Assuntos
COVID-19 , Trombose , Anticoagulantes/uso terapêutico , Aspirina , Enoxaparina/uso terapêutico , Humanos , Respiração Artificial , Estudos Retrospectivos , SARS-CoV-2 , Trombose/prevenção & controle
4.
Nutrients ; 13(6)2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34199189

RESUMO

Nattokinase (NK) is a serine protease enzyme with fibrinolytic activity. Even if it could be used for the treatment of several diseases, no data have been published supporting its use patients who underwent vascular surgery. In this study, we evaluated both the efficacy and the safety of nattokinase (100 mg/day per os) in patients admitted to vascular surgery. Patients were of both sexes, >18 years of age, with vascular diseases (i.e., deep vein thrombosis, superficial vein thrombosis, venous insufficiency), and naïve to specific pharmacological treatments (anticoagulants or anti-platelets). Patients were divided into three groups. Group 1: patients with deep vein thrombosis, treated with fondaparinux plus nattokinase. Group 2: patients with phlebitis, treated with enoxaparin plus nattokinase. Group 3: patients with venous insufficiency after classical surgery, treated with nattokinase one day later. During the study, we enrolled 153 patients (age 22-92 years), 92 females (60.1%) and 61 males (39.9%;), and documented that nattokinase was able to improve the clinical symptoms (p < 0.01) without the development of adverse drug reactions or drug interactions. Among the enrolled patients, during follow-up, we did not record new cases of vascular diseases. Attention to patients' clinical evolution, monitoring of the INR, and timely and frequent adjustment of dosages represent the cornerstones of the safety of care for patients administered fibrinolytic drugs as a single treatment or in pharmacological combination. Therefore, we can conclude that the use of nattokinase represents an efficient and safe treatment able to both prevent and treat patients with vascular diseases.


Assuntos
Fibrinolíticos/uso terapêutico , Subtilisinas/uso terapêutico , Insuficiência Venosa/tratamento farmacológico , Trombose Venosa/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Enoxaparina/uso terapêutico , Feminino , Fibrinolíticos/efeitos adversos , Fondaparinux/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Subtilisinas/efeitos adversos , Procedimentos Cirúrgicos Vasculares , Adulto Jovem
5.
Viruses ; 13(6)2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34205940

RESUMO

In recent weeks, adverse reactions have been reported after administration of Oxford-AstraZeneca chimpanzee adenovirus vectored vaccine ChAdOx1 nCoV-19 (AZD1222), in particular thrombus formation, which has led several European Countries to discontinue administration of this vaccine. On March 8, 2021, the European Medicines Agency Safety Committee did not confirm this probable association. We report the case of a patient who developed disseminated intravascular coagulation after the first dose of Oxford-Astra Zeneca vaccine, which resolved in a few days with the administration of dexamethasone and enoxaparin. This work demonstrates the safety of the Oxford-Astra Zeneca vaccine and that any development of side effects can be easily managed with a prompt diagnosis and in a short time with a few commonly used drugs.


Assuntos
Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/etiologia , COVID-19/imunologia , Técnicas de Laboratório Clínico , Dexametasona/uso terapêutico , Coagulação Intravascular Disseminada/tratamento farmacológico , Enoxaparina/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Vacinação
6.
Lancet ; 397(10291): 2253-2263, June. 2021. graf, tab
Artigo em Inglês | Sec. Est. Saúde SP, CONASS, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1283800

RESUMO

BACKGROUND: COVID-19 is associated with a prothrombotic state leading to adverse clinical outcomes. Whether therapeutic anticoagulation improves outcomes in patients hospitalised with COVID-19 is unknown. We aimed to compare the efficacy and safety of therapeutic versus prophylactic anticoagulation in this population. METHODS: We did a pragmatic, open-label (with blinded adjudication), multicentre, randomised, controlled trial, at 31 sites in Brazil. Patients (aged ≥18 years) hospitalised with COVID-19 and elevated D-dimer concentration, and who had COVID-19 symptoms for up to 14 days before randomisation, were randomly assigned (1:1) to receive either therapeutic or prophylactic anticoagulation. Therapeutic anticoagulation was in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3­0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30. Prophylactic anticoagulation was standard in-hospital enoxaparin or unfractionated heparin. The primary efficacy outcome was a hierarchical analysis of time to death, duration of hospitalisation, or duration of supplemental oxygen to day 30, analysed with the win ratio method (a ratio >1 reflects a better outcome in the therapeutic anticoagulation group) in the intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding through 30 days. This study is registered with ClinicalTrials.gov (NCT04394377) and is completed. FINDINGS: From June 24, 2020, to Feb 26, 2021, 3331 patients were screened and 615 were randomly allocated (311 [50%] to the therapeutic anticoagulation group and 304 [50%] to the prophylactic anticoagulation group). 576 (94%) were clinically stable and 39 (6%) clinically unstable. One patient, in the therapeutic group, was lost to follow-up because of withdrawal of consent and was not included in the primary analysis. The primary efficacy outcome was not different between patients assigned therapeutic or prophylactic anticoagulation, with 28 899 (34·8%) wins in the therapeutic group and 34 288 (41·3%) in the prophylactic group (win ratio 0·86 [95% CI 0·59­1·22], p=0·40). Consistent results were seen in clinically stable and clinically unstable patients. The primary safety outcome of major or clinically relevant non-major bleeding occurred in 26 (8%) patients assigned therapeutic anticoagulation and seven (2%) assigned prophylactic anticoagulation (relative risk 3·64 [95% CI 1·61­8·27], p=0·0010). Allergic reaction to the study medication occurred in two (1%) patients in the therapeutic anticoagulation group and three (1%) in the prophylactic anticoagulation group. INTERPRETATION: In patients hospitalised with COVID-19 and elevated D-dimer concentration, in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation. Therefore, use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Terapêutica , Coagulação Sanguínea , COVID-19 , Anticoagulantes , Produtos de Degradação da Fibrina e do Fibrinogênio , Heparina/uso terapêutico , Enoxaparina/uso terapêutico , Determinação de Ponto Final , Hemorragia/induzido quimicamente , Hospitalização
7.
Lancet ; 397(10291): 2253-2263, 2021 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-34097856

RESUMO

BACKGROUND: COVID-19 is associated with a prothrombotic state leading to adverse clinical outcomes. Whether therapeutic anticoagulation improves outcomes in patients hospitalised with COVID-19 is unknown. We aimed to compare the efficacy and safety of therapeutic versus prophylactic anticoagulation in this population. METHODS: We did a pragmatic, open-label (with blinded adjudication), multicentre, randomised, controlled trial, at 31 sites in Brazil. Patients (aged ≥18 years) hospitalised with COVID-19 and elevated D-dimer concentration, and who had COVID-19 symptoms for up to 14 days before randomisation, were randomly assigned (1:1) to receive either therapeutic or prophylactic anticoagulation. Therapeutic anticoagulation was in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3-0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30. Prophylactic anticoagulation was standard in-hospital enoxaparin or unfractionated heparin. The primary efficacy outcome was a hierarchical analysis of time to death, duration of hospitalisation, or duration of supplemental oxygen to day 30, analysed with the win ratio method (a ratio >1 reflects a better outcome in the therapeutic anticoagulation group) in the intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding through 30 days. This study is registered with ClinicalTrials.gov (NCT04394377) and is completed. FINDINGS: From June 24, 2020, to Feb 26, 2021, 3331 patients were screened and 615 were randomly allocated (311 [50%] to the therapeutic anticoagulation group and 304 [50%] to the prophylactic anticoagulation group). 576 (94%) were clinically stable and 39 (6%) clinically unstable. One patient, in the therapeutic group, was lost to follow-up because of withdrawal of consent and was not included in the primary analysis. The primary efficacy outcome was not different between patients assigned therapeutic or prophylactic anticoagulation, with 28 899 (34·8%) wins in the therapeutic group and 34 288 (41·3%) in the prophylactic group (win ratio 0·86 [95% CI 0·59-1·22], p=0·40). Consistent results were seen in clinically stable and clinically unstable patients. The primary safety outcome of major or clinically relevant non-major bleeding occurred in 26 (8%) patients assigned therapeutic anticoagulation and seven (2%) assigned prophylactic anticoagulation (relative risk 3·64 [95% CI 1·61-8·27], p=0·0010). Allergic reaction to the study medication occurred in two (1%) patients in the therapeutic anticoagulation group and three (1%) in the prophylactic anticoagulation group. INTERPRETATION: In patients hospitalised with COVID-19 and elevated D-dimer concentration, in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation. Therefore, use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation. FUNDING: Coalition COVID-19 Brazil, Bayer SA.


Assuntos
Anticoagulantes/uso terapêutico , COVID-19/sangue , COVID-19/tratamento farmacológico , Enoxaparina/uso terapêutico , Heparina/uso terapêutico , Rivaroxabana/efeitos adversos , Rivaroxabana/uso terapêutico , Adulto , Idoso , Coagulação Sanguínea/efeitos dos fármacos , Brasil/epidemiologia , Determinação de Ponto Final , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio , Hemorragia/induzido quimicamente , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , SARS-CoV-2 , Resultado do Tratamento
8.
BMJ ; 373: n1038, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33975825

RESUMO

OBJECTIVE: To investigate the use of repurposed and adjuvant drugs in patients admitted to hospital with covid-19 across three continents. DESIGN: Multinational network cohort study. SETTING: Hospital electronic health records from the United States, Spain, and China, and nationwide claims data from South Korea. PARTICIPANTS: 303 264 patients admitted to hospital with covid-19 from January 2020 to December 2020. MAIN OUTCOME MEASURES: Prescriptions or dispensations of any drug on or 30 days after the date of hospital admission for covid-19. RESULTS: Of the 303 264 patients included, 290 131 were from the US, 7599 from South Korea, 5230 from Spain, and 304 from China. 3455 drugs were identified. Common repurposed drugs were hydroxychloroquine (used in from <5 (<2%) patients in China to 2165 (85.1%) in Spain), azithromycin (from 15 (4.9%) in China to 1473 (57.9%) in Spain), combined lopinavir and ritonavir (from 156 (<2%) in the VA-OMOP US to 2,652 (34.9%) in South Korea and 1285 (50.5%) in Spain), and umifenovir (0% in the US, South Korea, and Spain and 238 (78.3%) in China). Use of adjunctive drugs varied greatly, with the five most used treatments being enoxaparin, fluoroquinolones, ceftriaxone, vitamin D, and corticosteroids. Hydroxychloroquine use increased rapidly from March to April 2020 but declined steeply in May to June and remained low for the rest of the year. The use of dexamethasone and corticosteroids increased steadily during 2020. CONCLUSIONS: Multiple drugs were used in the first few months of the covid-19 pandemic, with substantial geographical and temporal variation. Hydroxychloroquine, azithromycin, lopinavir-ritonavir, and umifenovir (in China only) were the most prescribed repurposed drugs. Antithrombotics, antibiotics, H2 receptor antagonists, and corticosteroids were often used as adjunctive treatments. Research is needed on the comparative risk and benefit of these treatments in the management of covid-19.


Assuntos
COVID-19/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Reposicionamento de Medicamentos/métodos , Demandas Administrativas em Assistência à Saúde/estatística & dados numéricos , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Azitromicina/uso terapêutico , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/virologia , Ceftriaxona/uso terapêutico , Criança , Pré-Escolar , China/epidemiologia , Estudos de Coortes , Combinação de Medicamentos , Registros Eletrônicos de Saúde/estatística & dados numéricos , Enoxaparina/uso terapêutico , Feminino , Fluoroquinolonas/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Lactente , Recém-Nascido , Pacientes Internados , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Ritonavir/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/genética , Segurança , Espanha/epidemiologia , Resultado do Tratamento , Estados Unidos/epidemiologia , Vitamina D/uso terapêutico , Adulto Jovem
11.
PLoS One ; 16(5): e0251966, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34015018

RESUMO

OBJECTIVE: The aim of this study was to assess the incidence of deep vein thrombosis (DVT) of the lower limbs, using serial compression ultrasound (CUS) surveillance, in acutely ill patients with COVID-19 pneumonia admitted to a non-ICU setting. METHODS: Multicenter, prospective study of patients with COVID-19 pneumonia admitted to Internal Medicine units. All patients were screened for DVT of the lower limbs with serial CUS. Anticoagulation was defined as: low dose (enoxaparin 20-40 mg/day or fondaparinux 1.5-2.5 mg/day); intermediate dose (enoxaparin 60-80 mg/day); high dose (enoxaparin 120-160 mg or fondaparinux 5-10 mg/day or oral anticoagulation). The primary end-point of the study was the diagnosis of DVT by CUS. RESULTS: Over a two-month period, 227 consecutive patients with moderate-severe COVID-19 pneumonia were enrolled. The incidence of DVT was 13.7% (6.2% proximal, 7.5% distal), mostly asymptomatic. All patients received anticoagulation (enoxaparin 95.6%) at the following doses: low 57.3%, intermediate 22.9%, high 19.8%. Patients with and without DVT had similar characteristics, and no difference in anticoagulant regimen was observed. DVT patients were older (mean 77±9.6 vs 71±13.1 years; p = 0.042) and had higher peak D-dimer levels (5403 vs 1723 ng/mL; p = 0.004). At ROC analysis peak D-dimer level >2000 ng/mL (AUC 0.703; 95% CI 0.572-0.834; p = 0.004) was the most accurate cut-off value able to predict DVT (RR 3.74; 95%CI 1.27-10, p = 0.016). CONCLUSIONS: The incidence of DVT in acutely ill patients with COVID-19 pneumonia is relevant. A surveillance protocol by serial CUS of the lower limbs is useful to timely identify DVT that would go otherwise largely undetected.


Assuntos
COVID-19/diagnóstico por imagem , Trombose Venosa/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , COVID-19/complicações , Enoxaparina/uso terapêutico , Feminino , Fondaparinux/uso terapêutico , Humanos , Incidência , Extremidade Inferior/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Ultrassonografia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/tratamento farmacológico , Trombose Venosa/etiologia
12.
Thromb Res ; 203: 117-120, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33992874

RESUMO

Venothrombolism (VTE) prophylaxis is increasingly utilized in pediatric intensive care units (PICUs). Enoxaparin, a low-molecular weight heparin, is frequently used for this purpose. Enoxaparin can also be used for therapeutic anticoagulation in cases of known thrombus. In such cases, monitoring involves obtaining serum anti- Xa levels with a target value of 0.5-1 units/mL. No monitoring recommendations currently exist for enoxaparin when intended for pediatric VTE prophylaxis. We hypothesize that a clinically important number of patients on VTE prophylaxis with enoxaparin have serum anti-Xa levels consistent with values targeted for therapeutic anticoagulation. We found that over 20% of patients on VTE prophylaxis with enoxaparin had serum anti-Xa levels consistent with true therapeutic anticoagulation (anti-Xa level 0.5-1 units/mL) during their enoxaparin course and 5% achieved values of supratherapeutic anticoagulation (anti-Xa level >1 units/mL). Serum anti-Xa level did not correlate with once versus twice daily dosing, body mass index (BMI), or creatinine level. Blood urea nitrogen (BUN) was found to have a positive odds ratio for an anti-Xa level ≥ 0.5 units/mL. We believe that this incidence of unintended therapeutic anticoagulation indicates a clinically significant number and therefore routine anti-Xa evaluation while on VTE prophylaxis is warranted within our population.


Assuntos
Enoxaparina , Tromboembolia Venosa , Anticoagulantes/uso terapêutico , Criança , Estado Terminal , Esquema de Medicação , Enoxaparina/uso terapêutico , Humanos , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle
13.
Am Heart J ; 238: 1-11, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33891907

RESUMO

BACKGROUND: Observational studies have suggested a higher risk of thrombotic events in patients with coronavirus disease 2019 (COVID-19). Moreover, elevated D-dimer levels have been identified as an important prognostic marker in COVID-19 directly associated with disease severity and progression. Prophylactic anticoagulation for hospitalized COVID-19 patients might not be enough to prevent thrombotic events; therefore, therapeutic anticoagulation regimens deserve clinical investigation. DESIGN: ACTION is an academic-led, pragmatic, multicenter, open-label, randomized, phase IV clinical trial that aims to enroll around 600 patients at 40 sites participating in the Coalition COVID-19 Brazil initiative. Eligible patients with a confirmed diagnosis of COVID-19 with symptoms up to 14 days and elevated D-dimer levels will be randomized to a strategy of full-dose anticoagulation for 30 days with rivaroxaban 20 mg once daily (or full-dose heparin if oral administration is not feasible) vs standard of care with any approved venous thromboembolism prophylaxis regimen during hospitalization. A confirmation of COVID-19 was mandatory for study entry, based on specific tests used in clinical practice (RT-PCR, antigen test, IgM test) collected before randomization, regardless of in the outpatient setting or not. Randomization will be stratified by clinical stability at presentation. The primary outcome is a hierarchical analysis of mortality, length of hospital stay, or duration of oxygen therapy at the end of 30 days. Secondary outcomes include the World Health Organization's 8-point ordinal scale at 30 days and the following efficacy outcomes: incidence of venous thromboembolism , acute myocardial infarction, stroke, systemic embolism, major adverse limb events, duration of oxygen therapy, disease progression, and biomarkers. The primary safety outcomes are major or clinically relevant non-major bleeding according to the International Society on Thrombosis and Haemostasis criteria. SUMMARY: The ACTION trial will evaluate whether in-hospital therapeutic anticoagulation with rivaroxaban for stable patients, or enoxaparin for unstable patients, followed by rivaroxaban through 30 days compared with standard prophylactic anticoagulation improves clinical outcomes in hospitalized patients with COVID-19 and elevated D-dimer levels.


Assuntos
Anticoagulantes/uso terapêutico , COVID-19/complicações , Enoxaparina/uso terapêutico , Rivaroxabana/uso terapêutico , Trombose/prevenção & controle , Administração Oral , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Brasil , COVID-19/sangue , COVID-19/mortalidade , Esquema de Medicação , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hemorragia/induzido quimicamente , Hospitalização , Humanos , Oxigenoterapia , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Trombose/etiologia , Fatores de Tempo
14.
Surg Obes Relat Dis ; 17(6): 1218-1225, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33814315

RESUMO

BACKGROUND: Venous thromboembolism (VTE) is one of the most common causes of postoperative mortality following bariatric surgery. The majority of VTE events occur after discharge from the hospital. Little consensus exists regarding who should receive extended enoxaparin thromboprophylaxis or how they should be dosed, namely whether to use weight-based or BMI-stratified dosing strategies. OBJECTIVES: Provide an overview of the risk factors associated with VTE in procedures among bariatric patients including the use of predictive tools to stratify risk and the various approaches to enoxaparin chemoprophylaxis in obesity. SETTING: Multiple centers. METHODS: A review of the literature identified studies evaluating risk factors for VTE including demographic characteristics, co-morbidities, and operative factors. The use of calculators to stratify patients by risk and approaches to extended thromboprophylaxis in obesity were evaluated as well. RESULTS: VTE was associated with increased age, weight, male sex, and prior history of VTE, all frequently included in risk calculators. Outside of those major risk factors, there is little consensus about the importance of patient diagnoses. Weight-based dosing was often superior to standardized dosing in studies across disciplines in generating target anti-Xa levels however there is no consistent association of reduced risk of VTE with therapeutic anti-Xa levels. CONCLUSIONS: Risk calculators may be a valuable tool for identifying patients at high-risk for VTE, but their efficacy depends on the rating algorithm and inclusion of various risk factors and is methodologically limited by prophylactic interventions. Future work should consider if biochemical factors should be included in patient stratification approaches in particular when defining the ideal chemoprophylaxis approach. Transparency and consistency in data collection and reporting is needed to better assess and inform the ideal dosing strategy to prevent VTE following bariatric surgery.


Assuntos
Cirurgia Bariátrica , Tromboembolia Venosa , Assistência ao Convalescente , Anticoagulantes/uso terapêutico , Cirurgia Bariátrica/efeitos adversos , Enoxaparina/uso terapêutico , Humanos , Masculino , Alta do Paciente , Fatores de Risco , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
15.
Vopr Virusol ; 66(1): 47-54, 2021 03 07.
Artigo em Russo | MEDLINE | ID: mdl-33683065

RESUMO

INTRODUCTION: Interferons are produced in response to the presence of pathogens in cells and are responsible for the proper formation of immune reaction. Preliminary data obtained in studies of properties of recombinant interferon gamma (IFN-γ) that involved patients with community-acquired pneumonia (including bacterial), acute respiratory viral infection (ARVI), influenza and new coronavirus infection have shown promising results.The purpose of the study was to assess the effect of subcutaneous administration of IFN-γ in patients with viral pneumonia on the changes of vital signs and the duration of hospital stay. MATERIAL AND METHODS: An open-label, randomized, low-interventional study included patients with moderate new coronavirus infection COVID-19 over 18 years of age of both sexes. IFN-γ 500,000 IU was administered s/c, daily, once a day, during 5 days. RESULTS: IFN-y in addition to complex therapy of the disease resulted in more favorable changes in the stabilization of vital signs, as well as in reduced length of fever and hospital stay by 2 days what allows suggesting a positive effect of this substance on the recovery processes in patients with moderate COVID-19. Special emphasis should be made to the fact that patients who received recombinant IFN- γ experienced no progression of respiratory failure and required no transfer to intensive care unit. DISCUSSION: This study confirms earlier obtained data on the positive effect of IFN-y on the rate of clinical stabilization and recovery of patients with community-acquired pneumonia and viral infections. Presented results are limited to a small number of patients; further study of drug properties in post-marketing studies is required. CONCLUSION: Progress in the treatment of patients with moderate COVID-19 by adding recombinant IFN-γ to the complex therapy may reasonably expand the range of existing treatment options for this infection.


Assuntos
Anti-Infecciosos/uso terapêutico , Anticoagulantes/uso terapêutico , COVID-19/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Interferon gama/uso terapêutico , Idoso , Ampicilina/uso terapêutico , Azitromicina/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , COVID-19/imunologia , COVID-19/patologia , COVID-19/virologia , Enoxaparina/uso terapêutico , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença , Resultado do Tratamento , Vancomicina/uso terapêutico
16.
J Med Virol ; 93(7): 4303-4318, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33666246

RESUMO

Here we analyze hospitalized andintensive care unit coronavirus disease 2019 (COVID-19) patient outcomes from the international VIRUS registry (https://clinicaltrials.gov/ct2/show/NCT04323787). We find that COVID-19 patients administered unfractionated heparin but not enoxaparin have a higher mortality-rate (390 of 1012 = 39%) compared to patients administered enoxaparin but not unfractionated heparin (270 of 1939 = 14%), presenting a risk ratio of 2.79 (95% confidence interval [CI]: [2.42, 3.16]; p = 4.45e-52). This difference persists even after balancing on a number of covariates including demographics, comorbidities, admission diagnoses, and method of oxygenation, with an increased mortality rate on discharge from the hospital of 37% (268 of 733) for unfractionated heparin versus 22% (154 of 711) for enoxaparin, presenting a risk ratio of 1.69 (95% CI: [1.42, 2.00]; p = 1.5e-8). In these balanced cohorts, a number of complications occurred at an elevated rate for patients administered unfractionated heparin compared to patients administered enoxaparin, including acute kidney injury, acute cardiac injury, septic shock, and anemia. Furthermore, a higher percentage of Black/African American COVID patients (414 of 1294 [32%]) were noted to receive unfractionated heparin compared to White/Caucasian COVID patients (671 of 2644 [25%]), risk ratio 1.26 (95% CI: [1.14, 1.40]; p = 7.5e-5). After balancing upon available clinical covariates, this difference in anticoagulant use remained statistically significant (311 of 1047 [30%] for Black/African American vs. 263 of 1047 [25%] for White/Caucasian, p = .02, risk ratio 1.18; 95% CI: [1.03, 1.36]). While retrospective studies cannot suggest any causality, these findings motivate the need for follow-up prospective research into the observed racial disparity in anticoagulant use and outcomes for severe COVID-19 patients.


Assuntos
Anticoagulantes/uso terapêutico , COVID-19/mortalidade , Enoxaparina/uso terapêutico , Disparidades em Assistência à Saúde , Heparina/uso terapêutico , Trombose/prevenção & controle , Anticoagulantes/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , COVID-19/sangue , COVID-19/tratamento farmacológico , Enoxaparina/efeitos adversos , Feminino , Heparina/efeitos adversos , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Trombose/tratamento farmacológico
17.
Rev. iberoam. micol ; 38(1): 16-18, ene.-mar. 2021. ilus
Artigo em Inglês | IBECS | ID: ibc-202390

RESUMO

BACKGROUND: Patients with severe viral pneumonia are likely to receive high-dose immunomodulatory drugs to prevent clinical worsening. Aspergillus species have been described as frequent secondary pneumonia agents in severely ill influenza patients receiving steroids. COVID-19 patients admitted to Intensive Care Unit (ICU) are receiving steroids as part of their treatment and they share clinical characteristics with other patients with severe viral pneumonias. COVID-19 patients receiving steroids should be considered a putative risk group of invasive aspergillosis. CASE REPORT: We are reporting a SARS-CoV-2/Aspergillus section Fumigati coinfection in an elderly intubated patient with a history of pulmonary embolism treated with corticosteroids. The diagnosis was made following the ad hoc definitions described for patients admitted to ICU with severe influenza, including clinical criteria (fever for 3 days refractory to the appropriate antibiotic therapy, dyspnea, pleural friction rub, worsening of respiratory status despite antibiotic therapy and need of ventilator support), a radiological criterion (pulmonary infiltrate) and a mycological criterion (several positive galactomannan tests on serum with ratio ≥0.5). In addition, Aspergillus section Fumigati DNA was found in serum and blood samples. These tests were positive 4 weeks after the patient was admitted to the ICU. The patient received voriconazole and after two month in ICU his respiratory status improved; he was discharged after 6 weeks of antifungal treatment. CONCLUSIONS: Severely ill COVID-19 patients would be considered a new aspergillosis risk group. Galactomannan and Aspergillus DNA detection would be useful methods for Aspergillus infection diagnosis as they allow avoiding the biosafety issues related to these patients


ANTECEDENTES: Los pacientes con neumonía viral grave reciben altas dosis de fármacos inmunomoduladores para prevenir el empeoramiento clínico. Los pacientes con influenza grave que reciben esteroides tienen neumonías secundarias causadas por Aspergillus con una frecuencia relativamente alta. Los pacientes con COVID-19 ingresados en la unidad de cuidados intensivos (UCI) reciben dicha medicación como parte de su tratamiento, y comparten con otro tipo de pacientes muchas de las características clínicas de otras neumonías virales graves. Estos pacientes deberían considerarse como un grupo de riesgo de aspergilosis invasiva. CASO CLÍNICO: Se presenta un caso de coinfección por SARS-CoV-2 y Aspergillus de la sección Fumigati en un paciente intubado de edad avanzada con antecedentes de embolia pulmonar y tratado con corticosteroides. El diagnóstico siguió las definiciones ad hoc descritas para pacientes ingresados en la UCI con gripe grave. El paciente cumplía varios criterios clínicos (fiebre durante 3 días refractaria al tratamiento antibiótico apropiado, disnea, fricción pleural, empeoramiento del estado respiratorio a pesar del tratamiento antibiótico y la necesidad de soporte respiratorio), el criterio radiológico (infiltrado pulmonar) y un criterio micológico (test de galactomanano positivo en suero, (ratio ≥0,5). Además, se detectó ADN de Aspergillus de la sección Fumigati en muestras de suero y sangre del paciente. Estas pruebas fueron positivas 4 semanas después de que el paciente ingresara en la UCI. El paciente recibió tratamiento con voriconazol, y después de 2 meses en la UCI mejoró su estado pulmonar; fue dado de alta después de 6 semanas de tratamiento antifúngico. CONCLUSIONES: Los pacientes gravemente enfermos con COVID-19 deberían considerarse un nuevo grupo de riesgo para la aspergilosis. La detección de galactomanano y ADN de Aspergillus son métodos útiles para el diagnóstico de infección por este hongo al evitar los problemas de bioseguridad en estos pacientes


Assuntos
Humanos , Masculino , Idoso , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Aspergillus fumigatus/isolamento & purificação , Imunocompetência , Imunossupressores/efeitos adversos , Aspergilose Pulmonar/complicações , Metilprednisolona/efeitos adversos , Vírus da SARS/isolamento & purificação , Infecções por Coronavirus/virologia , Acetaminofen/uso terapêutico , Anti-Infecciosos/uso terapêutico , Coinfecção/microbiologia , Enoxaparina/uso terapêutico , Hidroxicloroquina/uso terapêutico , Imunossupressores/uso terapêutico , Aspergilose Pulmonar/microbiologia , Metilprednisolona/uso terapêutico , Pseudomonas aeruginosa/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real
18.
BMJ Case Rep ; 14(3)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33727290

RESUMO

We present a case of a giant ovarian cyst in a 20-year-old woman who presented atypically at our Emergency Department with left-sided back pain followed by acute left leg swelling. Blood tests showed significantly raised C-Reactive Protein and D-Dimer. CT-Abdomen-Pelvis demonstrated a large mass in the region of the right ovary with suspicious heterogeneous filling defects in the left external iliac vein, confirmed as a left-sided deep-vein thrombosis on ultrasound Doppler. MRI revealed the lesion to be cystic and the deep venous thrombosis was treated with twice-daily Clexane. Prior to removal of the cyst, an Inferior Vena Cava Filter was placed to reduce thromboembolic risk. The cyst was resected without complication and the postoperative period was uneventful. This case occurred while face-to-face services were limited by COVID-19 and illustrates the need for robust systemic measures to safeguard patients against the emergency sequelae of insidious gynaecological pathology.


Assuntos
Dor nas Costas/etiologia , Diagnóstico por Imagem/métodos , Cistos Ovarianos/complicações , Cistos Ovarianos/diagnóstico por imagem , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologia , Adulto , Diagnóstico Diferencial , Enoxaparina/uso terapêutico , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Perna (Membro) , Imageamento por Ressonância Magnética , Cistos Ovarianos/cirurgia , Ovário/diagnóstico por imagem , Ovário/cirurgia , Tomografia Computadorizada por Raios X , Ultrassonografia Doppler , Trombose Venosa/tratamento farmacológico , Adulto Jovem
19.
Crit Care Med ; 49(4): e369-e380, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33566465

RESUMO

OBJECTIVES: We explored the age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin against central venous catheter-associated deep venous thrombosis in critically ill children. DESIGN: Post hoc analysis of a Bayesian phase 2b randomized clinical trial. SETTING: Seven PICUs. PATIENTS: Children less than 18 years old with newly inserted central venous catheter. INTERVENTIONS: Enoxaparin started less than 24 hours after insertion of central venous catheter and adjusted to anti-Xa level of 0.2-0.5 international units/mL versus usual care. MEASUREMENTS AND MAIN RESULTS: Of 51 children randomized, 24 were infants less than 1 year old. Risk ratios of central venous catheter-associated deep venous thrombosis with prophylaxis with enoxaparin were 0.98 (95% credible interval, 0.37-2.44) in infants and 0.24 (95% credible interval, 0.04-0.82) in older children greater than or equal to 1 year old. Infants and older children achieved anti-Xa level greater than or equal to 0.2 international units/mL at comparable times. While central venous catheter was in situ, endogenous thrombin potential, a measure of thrombin generation, was 223.21 nM.min (95% CI, 8.78-437.64 nM.min) lower in infants. Factor VIII activity, a driver of thrombin generation, was also lower in infants by 45.1% (95% CI, 15.7-74.4%). Median minimum platelet count while central venous catheter was in situ was higher in infants by 39 × 103/mm3 (interquartile range, 17-61 × 103/mm3). Central venous catheter:vein ratio was not statistically different. Prophylaxis with enoxaparin was less efficacious against central venous catheter-associated deep venous thrombosis at lower factor VIII activity and at higher platelet count. CONCLUSIONS: The relatively lesser contribution of thrombin generation on central venous catheter-associated thrombus formation in critically ill infants potentially explains the age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin.


Assuntos
Anticoagulantes/uso terapêutico , Cateterismo Venoso Central/efeitos adversos , Estado Terminal/terapia , Enoxaparina/uso terapêutico , Trombose Venosa/prevenção & controle , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Avaliação de Resultados em Cuidados de Saúde , Profilaxia Pré-Exposição/estatística & dados numéricos , Trombose/prevenção & controle
20.
Am J Gastroenterol ; 116(7): 1447-1464, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33630766

RESUMO

INTRODUCTION: Current guidelines recommend anticoagulation as the mainstay of portal vein thrombosis (PVT) treatment in cirrhosis. However, because of the heterogeneity of PVT, anticoagulation alone does not always achieve satisfactory results. This study aimed to prospectively evaluate an individualized management algorithm using a wait-and-see strategy (i.e., no treatment), anticoagulation, and transjugular intrahepatic portosystemic shunt (TIPS) to treat PVT in cirrhosis. METHODS: Between February 2014 and June 2018, 396 consecutive patients with cirrhosis with nonmalignant PVT were prospectively included in a tertiary care center, of which 48 patients (12.1%) were untreated, 63 patients (15.9%) underwent anticoagulation, 88 patients (22.2%) underwent TIPS, and 197 patients (49.8%) received TIPS plus post-TIPS anticoagulation. The decision of treatment option mainly depends on the stage of liver disease (symptomatic portal hypertension or not) and degree and extension of thrombus. RESULTS: During a median 31.7 months of follow-up period, 312 patients (81.3%) achieved partial (n = 25) or complete (n = 287) recanalization, with 9 (3.1%) having rethrombosis, 64 patients (16.2%) developed major bleeding (anticoagulation-related bleeding in 7 [1.8%]), 88 patients (22.2%) developed overt hepatic encephalopathy, and 100 patients (25.3%) died. In multivariate competing risk regression models, TIPS and anticoagulation were associated with a higher probability of recanalization. Long-term anticoagulation using enoxaparin or rivaroxaban rather than warfarin was associated with a decreased risk of rethrombosis and an improved survival, without increasing the risk of bleeding. However, the presence of complete superior mesenteric vein thrombosis was associated with a lower recanalization rate, increased risk of major bleeding, and poor prognosis. DISCUSSION: In patients with cirrhosis with PVT, the individualized treatment algorithm achieves a high-probability recanalization, with low rates of portal hypertensive complications and adverse events.


Assuntos
Anticoagulantes/uso terapêutico , Hemorragia/epidemiologia , Encefalopatia Hepática/epidemiologia , Mortalidade , Veia Porta , Derivação Portossistêmica Transjugular Intra-Hepática/métodos , Trombose/terapia , Conduta Expectante , Adulto , Idoso , Algoritmos , Terapia Combinada , Enoxaparina/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Rivaroxabana/uso terapêutico , Índice de Gravidade de Doença , Trombose/etiologia , Varfarina/uso terapêutico
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