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1.
BMJ Case Rep ; 14(10)2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620636

RESUMO

Wunderlich syndrome is a rare condition characterised by acute spontaneous non-traumatic renal haemorrhage into the subcapsular and perirenal spaces. Our case of anti-GAD65-associated autoimmune encephalitis (AE), aged 30 years, developed this complication following use of enoxaparin and was managed by selective glue embolisation of subsegmental branches of right renal cortical arteries. Our case had opsoclonus as one of the clinical manifestations, which has till now been described in only two patients of this AE. This patient received all forms of induction therapies (steroids, plasmapheresis, intravenous immunoglobulin and rituximab) following which she had good improvement in her clinical condition. The good response to immunotherapy is also a point of discussion as this has been rarely associated with anti-GAD65 AE.


Assuntos
Encefalite , Encefalite Límbica , Transtornos da Motilidade Ocular , Enoxaparina/efeitos adversos , Feminino , Humanos , Doenças Raras
3.
J Thromb Haemost ; 19(9): 2225-2234, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34236768

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with coagulopathy but the optimal prophylactic anticoagulation therapy remains uncertain and may depend on COVID-19 severity. OBJECTIVE: To compare outcomes in hospitalized adults with severe COVID-19 treated with standard prophylactic versus intermediate dose enoxaparin. METHODS: We conducted a multi-center, open-label, randomized controlled trial comparing standard prophylactic dose versus intermediate dose enoxaparin in adults who were hospitalized with COVID-19 and admitted to an intensive care unit (ICU) and/or had laboratory evidence of coagulopathy. Patients were randomly assigned in a 1:1 ratio to receive standard prophylactic dose enoxaparin or intermediate weight-adjusted dose enoxaparin. The primary outcome was all-cause mortality at 30 days. Secondary outcomes included arterial or venous thromboembolism and major bleeding. RESULTS: A total of 176 patients (99 males and 77 females) underwent randomization. In the intention-to-treat population, all-cause mortality at 30 days was 15% for intermediate dose enoxaparin and 21% for standard prophylactic dose enoxaparin (odds ratio, 0.66; 95% confidence interval, 0.30-1.45; P = .31 by Chi-square test). Unadjusted Cox proportional hazards modeling demonstrated no significant difference in mortality between intermediate and standard dose enoxaparin (hazard ratio, 0.67; 95% confidence interval, 0.33-1.37; P = .28). Arterial or venous thrombosis occurred in 13% of patients assigned to intermediate dose enoxaparin and 9% of patients assigned to standard dose enoxaparin. Major bleeding occurred in 2% of patients in each arm. CONCLUSION: In hospitalized adults with severe COVID-19, standard prophylactic dose and intermediate dose enoxaparin did not differ significantly in preventing death or thrombosis at 30 days.


Assuntos
COVID-19 , Trombose , Adulto , Anticoagulantes/efeitos adversos , Enoxaparina/efeitos adversos , Feminino , Humanos , Masculino , SARS-CoV-2
4.
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
5.
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
6.
JAMA ; 325(16): 1620-1630, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33734299

RESUMO

Importance: Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis. Objective: To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized trial with a 2 × 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020. Interventions: Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. Main Outcomes and Measures: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 ×103/µL). All outcomes were blindly adjudicated. Results: Among 600 randomized patients, 562 (93.7%) were included in the primary analysis (median [interquartile range] age, 62 [50-71] years; 237 [42.2%] women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% [95% CI, -6.6% to 9.8%]; odds ratio, 1.06 [95% CI, 0.76-1.48]; P = .70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% [1-sided 97.5% CI, -∞ to 3.4%]; odds ratio, 1.83 [1-sided 97.5% CI, 0.00-5.93]), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% [95% CI, 0.4%-3.8%]; P = .01). Conclusions and Relevance: Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04486508.


Assuntos
Anticoagulantes/administração & dosagem , COVID-19/complicações , Enoxaparina/administração & dosagem , Oxigenação por Membrana Extracorpórea , Oxigenoterapia/métodos , Trombose/prevenção & controle , Idoso , Anticoagulantes/efeitos adversos , COVID-19/mortalidade , Esquema de Medicação , Enoxaparina/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Hospitalização , Humanos , Unidades de Terapia Intensiva , Irã (Geográfico) , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Avaliação de Resultados em Cuidados de Saúde , Embolia Pulmonar/epidemiologia , Trombocitopenia/induzido quimicamente , Trombose/etiologia , Trombose/mortalidade , Resultado do Tratamento , Trombose Venosa/epidemiologia , Trombose Venosa/mortalidade
7.
Medicine (Baltimore) ; 100(11): e25216, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33726018

RESUMO

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) have been widely used for stroke prevention in atrial fibrillation (AF) and the treatment and prevention of venous thromboembolism. There is an issue with safety, especially in clinically relevant bleeding. We performed a network meta-analysis to evaluate the risk of major gastrointestinal (GI) bleeding associated with NOACs. METHODS: Interventions were warfarin, enoxaparin, apixaban, dabigatran, edoxaban, and rivaroxaban. The primary outcome was the incidence of major GI bleeding. A subgroup analysis was performed according to the following indications: AF, deep venous thrombosis/pulmonary embolism, and postsurgical prophylaxis. RESULTS: A total of 29 randomized controlled trials (RCTs) and 4 large observation population studies were included. Compared with warfarin, apixaban showed a decreased the risk of major GI bleeding (relative risk [RR] 0.54, 95% confidence interval [CI] 0.25-0.76), and rivaroxaban tended to increase this risk (RR 1.40, 95% CI 1.06-1.85). Dabigatran (RR 1.25, 95% CI 0.98-1.60), edoxaban (RR 1.07, 95% CI 0.69-1.65), and enoxaparin (RR 1.24, 95% CI 0.63-2.43) did not significantly increase the risk of GI bleeding than did warfarin. In the subgroup analysis, according to indications, apixaban showed a decreased risk of major GI bleeding (RR 0.50, 95% CI 0.34-0.74) than did warfarin in AF studies. Dabigatran (RR 2.36, 95% CI 1.55-3.60, and rivaroxaban (RR 1.75, 95% CI 1.10-6.41) increased the risk of major GI bleeding than did apixaban. An analysis of studies on venous thromboembolism or pulmonary embolism showed that no individual NOAC or enoxaparin was associated with an increased risk of major GI bleeding compared to warfarin. CONCLUSION: Individual NOACs had varying profiles of GI bleeding risk. Results of analyses including only RCTs and those including both RCTs and population studies showed similar trends, but also showed several differences.


Assuntos
Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Hemorragia Gastrointestinal/induzido quimicamente , Embolia Pulmonar/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Adulto , Idoso , Fibrilação Atrial/complicações , Dabigatrana/efeitos adversos , Enoxaparina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metanálise em Rede , Estudos Observacionais como Assunto , Embolia Pulmonar/complicações , Pirazóis/efeitos adversos , Piridinas/efeitos adversos , Piridonas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Tiazóis/efeitos adversos , Tromboembolia Venosa/complicações , Varfarina/efeitos adversos
8.
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
10.
BMJ ; 372: n311, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33574135

RESUMO

OBJECTIVE: To evaluate whether early initiation of prophylactic anticoagulation compared with no anticoagulation was associated with decreased risk of death among patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United States. DESIGN: Observational cohort study. SETTING: Nationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated national healthcare system. PARTICIPANTS: All 4297 patients admitted to hospital from 1 March to 31 July 2020 with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and without a history of anticoagulation. MAIN OUTCOME MEASURES: The main outcome was 30 day mortality. Secondary outcomes were inpatient mortality, initiating therapeutic anticoagulation (a proxy for clinical deterioration, including thromboembolic events), and bleeding that required transfusion. RESULTS: Of 4297 patients admitted to hospital with covid-19, 3627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3600) of treated patients received subcutaneous heparin or enoxaparin. 622 deaths occurred within 30 days of hospital admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospital stay. Using inverse probability of treatment weighted analyses, the cumulative incidence of mortality at 30 days was 14.3% (95% confidence interval 13.1% to 15.5%) among those who received prophylactic anticoagulation and 18.7% (15.1% to 22.9%) among those who did not. Compared with patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30 day mortality (hazard ratio 0.73, 95% confidence interval 0.66 to 0.81). Similar associations were found for inpatient mortality and initiation of therapeutic anticoagulation. Receipt of prophylactic anticoagulation was not associated with increased risk of bleeding that required transfusion (hazard ratio 0.87, 0.71 to 1.05). Quantitative bias analysis showed that results were robust to unmeasured confounding (e-value lower 95% confidence interval 1.77 for 30 day mortality). Results persisted in several sensitivity analyses. CONCLUSIONS: Early initiation of prophylactic anticoagulation compared with no anticoagulation among patients admitted to hospital with covid-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events. These findings provide strong real world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with covid-19 on hospital admission.


Assuntos
Anticoagulantes/uso terapêutico , COVID-19/mortalidade , Enoxaparina/uso terapêutico , Tromboembolia/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , COVID-19/complicações , Enoxaparina/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , SARS-CoV-2 , Tromboembolia/virologia , Fatores de Tempo , Estados Unidos/epidemiologia
11.
Laryngoscope ; 131(9): 1946-1951, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33533493

RESUMO

OBJECTIVE/HYPOTHESIS: Anticoagulant and antiplatelet medications (ACAP) are known to be associated with an increased risk for epistaxis. There are conflicting results regarding the impact of Novel Oral Anticoagulants (NOAC) on epistaxis and its severity. STUDY DESIGN: Retrospective chart review of patients who were admitted to the ED in our tertiary level hospital with a diagnosis of epistaxis during the years 2012 to 2018. METHODS: Retrospective analysis of patients presenting to tertiary level emergency otolaryngological care during the years 2012 to 2018. The impact of various ACAP medications on epistaxis severity, hospital admission, and recurrence was analyzed. RESULTS: A total of 470 patients were identified. Two hundred and twenty-nine patients (49%), were not on any anticoagulant/antiplatelet (ACAP) medications (controls) and 241 patients (51%) were taking at least one ACAP medication (ACAP group). Patients in the ACAP group were at a higher risk for severe epistaxis (OR = 1.8, P < .05) and were more likely to be hospitalized (OR = 2.17, P < .05). Surprisingly, the risk for recurrence was similar in the ACAP and control groups (15%, P > .05). Compared to controls, Warfarin and Enoxaparin increased the overall risk for severe epistaxis (OR = 4.4, P < .05) and for hospital admission (OR = 2.1, P < .05). Specifically, an increased risk for posterior tamponade (OR = 19, P < .001), significant blood loss (OR = 4.4, P = .032), and blood transfusion (OR = 4.7, P = .007) were identified as well. Interestingly, NOACs were not associated with increased risk for severe epistaxis, hospital admission, tamponade, and significant blood loss or blood transfusion compared to controls. CONCLUSIONS: Compared to older generation anticoagulants and antiplatelet medications, NOACs demonstrated an improved safety profile, in terms of epistaxis severity, need for hospital admission and outcomes. These results may suggest a more conservative approach and less hospitalization when treating epistaxis in patients receiving NOACs. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1946-1951, 2021.


Assuntos
Anticoagulantes/efeitos adversos , Epistaxe/induzido quimicamente , Inibidores do Fator Xa/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Varfarina/efeitos adversos , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Estudos de Casos e Controles , Enoxaparina/efeitos adversos , Epistaxe/diagnóstico , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Inibidores da Agregação Plaquetária/administração & dosagem , Recidiva , Estudos Retrospectivos , Segurança , Índice de Gravidade de Doença , Varfarina/administração & dosagem
13.
Ann Pharmacother ; 55(9): 1120-1126, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33455432

RESUMO

BACKGROUND: Venous thromboembolism (VTE) is a complication of cancer, for which low-molecular-weight heparin (LMWH) remains the preferred anticoagulant. Enoxaparin is traditionally dosed using weight. In certain populations, monitoring anti-Xa levels for therapeutic effect provides pharmacokinetic guidance for dose adjustments. There is a paucity of data regarding anti-Xa-directed enoxaparin dosing for treatment of VTE in patients with cancer. OBJECTIVE: This study aims to evaluate efficacy (recurrent VTE) and safety (major bleed) between enoxaparin anti-Xa-guided dose adjustments and weight-based dosing in patients with cancer-associated VTE. METHODS: This single-center, retrospective cohort study examined patients treated with enoxaparin for cancer-associated VTE using data from electronic health records. RESULTS: There were 674 patients who met the inclusion criteria, with 283 receiving anti-Xa-directed dose adjustments. Recurrent VTE, major bleed, or all-cause death occurred in 102 of 283 patients (36%) in the anti-Xa cohort and 166 of 391 patients (42.5%) in the weight-based cohort (hazard ratio [HR] = 0.73; 95% CI = 0.57-0.93; P = 0.01). When death was removed from the composite end point, there was no significant difference between the cohorts in recurrent VTE or major bleed (HR = 1.18; P = 0.38). In the anti-Xa cohort, a total of 1584 anti-Xa peak levels were collected, with 1324 (83.6%) drawn correctly in relation to enoxaparin administration. Of those, 714 (53.9%) were within therapeutic range. CONCLUSION AND RELEVANCE: Patients with cancer receiving anti-Xa-guided enoxaparin dose adjustments for initial VTE, compared with weight-based dosing, had no significant difference in the rate of recurrent VTE or major bleed.


Assuntos
Neoplasias , Tromboembolia Venosa , Anticoagulantes/efeitos adversos , Enoxaparina/efeitos adversos , Inibidores do Fator Xa/efeitos adversos , Heparina de Baixo Peso Molecular , Humanos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Estudos Retrospectivos , Tromboembolia Venosa/tratamento farmacológico
16.
J Thromb Thrombolysis ; 51(2): 286-292, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32794132

RESUMO

Coagulopathy represents one of the most important determinants of morbidity and mortality in coronavirus disease-19 (COVID-19). Whether standard thromboprophylaxis is sufficient or higher doses are needed, especially in severe patients, is unknown. To evaluate the safety of intermediate dose regimens of low-weight molecular heparin (LWMH) in COVID-19 patients with pneumonia, particularly in older patients. We retrospectively evaluated 105 hospitalized patients (61 M, 44 F; mean age 73.7 years) treated with subcutaneous enoxaparin: 80 mg/day in normal weight and mild-to-moderate impair or normal renal function; 40 mg/day in severe chronic renal failure or low bodyweight (< 45 kg); 100 mg/day if bodyweight was higher than 100 kg. All the patients had radiologically confirmed pneumonia and 63.8% had severe COVID-19. None of the patients had fatal haemorrhage; two (1.9%) patients had a major bleeding event (one spontaneous hematoma and one gastrointestinal bleeding). Only 6.7% of patients needed transfusions of red blood cells. One thrombotic event (pulmonary embolism) was observed. When compared to younger patients, patients older than 85 years had a higher mortality (40% vs 13.3%), but not an increased risk of bleeding or need for blood transfusion. The use of an intermediate dose of LWMH appears to be feasible and data suggest safety in COVID-19 patients, although further studies are needed.


Assuntos
COVID-19/tratamento farmacológico , Enoxaparina/administração & dosagem , SARS-CoV-2 , Trombose/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , COVID-19/etiologia , COVID-19/mortalidade , Enoxaparina/efeitos adversos , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Falência Renal Crônica/complicações , Falência Renal Crônica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombose/etiologia
18.
Crit Care Med ; 49(3): e235-e246, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33372745

RESUMO

OBJECTIVES: We obtained preliminary evidence on the efficacy of early prophylaxis on the risk of central venous catheter-associated deep venous thrombosis and its effect on thrombin generation in critically ill children. DESIGN: Bayesian phase 2b randomized clinical trial. SETTING: Seven PICUs. PATIENTS: Children less than 18 years old with a newly inserted central venous catheter and at low risk of bleeding. INTERVENTION: Enoxaparin adjusted to anti-Xa level of 0.2-0.5 international units/mL started at less than 24 hours after insertion of central venous catheter (enoxaparin arm) versus usual care without placebo (usual care arm). MEASUREMENTS AND MAIN RESULTS: At the interim analysis, the proportion of central venous catheter-associated deep venous thrombosis on ultrasonography in the usual care arm, which was 54.2% of 24 children, was significantly higher than that previously reported. This resulted in misspecification of the preapproved Bayesian analysis, reversal of direction of treatment effect, and early termination of the randomized clinical trial. Nevertheless, with 30.4% of 23 children with central venous catheter-associated deep venous thrombosis on ultrasonography in the enoxaparin arm, risk ratio of central venous catheter-associated deep venous thrombosis was 0.55 (95% credible interval, 0.24-1.11). Including children without ultrasonography, clinically relevant central venous catheter-associated deep venous thrombosis developed in one of 27 children (3.7%) in the enoxaparin arm and seven of 24 (29.2%) in the usual care arm (p = 0.02). Clinically relevant bleeding developed in one child randomized to the enoxaparin arm. Response profile of endogenous thrombin potential, a measure of thrombin generation, was not statistically different between trial arms. CONCLUSIONS: These findings suggest the efficacy and safety of early prophylaxis that should be validated in a pivotal randomized clinical trial.


Assuntos
Anticoagulantes/administração & dosagem , Cateterismo Venoso Central/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Enoxaparina/administração & dosagem , Trombose Venosa/prevenção & controle , Adolescente , Anticoagulantes/efeitos adversos , Teorema de Bayes , Criança , Pré-Escolar , Estado Terminal , Método Duplo-Cego , Esquema de Medicação , Enoxaparina/efeitos adversos , Humanos , Masculino , Profilaxia Pré-Exposição
19.
J Cardiovasc Pharmacol ; 76(4): 369-371, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33027192

RESUMO

The use of heparin has been shown to decrease the mortality in hospitalized patients with severe COVID-19. The aim of our study was to evaluate the clinical impact of venous thromboembolism prophylaxis with fondaparinux versus enoxaparin among 100 hospitalized COVID-19 patients. The incidence of pulmonary embolism, deep venous thrombosis, major bleeding (MB), clinically relevant non-MB, acute respiratory distress syndrome, and in-hospital mortality was compared between patients on fondaparinux versus enoxaparin therapy. The 2 groups were homogeneous for demographic, laboratory, and clinical characteristics. In a median follow-up of 28 (IQR: 12-45) days, no statistically significant difference in venous thromboembolism (14.5% vs. 5.3%; P = 0.20), MB and clinically relevant non-MB (3.2% vs. 5.3%, P = 0.76), ARDS (17.7% vs. 15.8%; P = 0.83), and in-hospital mortality (9.7% vs. 10.5%; P = 0.97) has been shown between the enoxaparin group versus the fondaparinux group. Our preliminary results support the hypothesis of a safe and effective use of fondaparinux among patients with COVID-19 hospitalized in internal medicine units.


Assuntos
Antitrombinas/uso terapêutico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Fondaparinux/uso terapêutico , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Trombose Venosa/etiologia , Trombose Venosa/prevenção & controle , Idoso , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Antitrombinas/efeitos adversos , COVID-19 , Enoxaparina/efeitos adversos , Enoxaparina/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Feminino , Fondaparinux/efeitos adversos , Hemorragia/induzido quimicamente , Mortalidade Hospitalar , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pandemias , Embolia Pulmonar/complicações , Estudos Retrospectivos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/prevenção & controle , Trombose Venosa/epidemiologia
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