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1.
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 , 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
2.
Rev Med Suisse ; 16(706): 1718-1720, 2020 Sep 16.
Artigo em Francês | MEDLINE | ID: mdl-32936558

RESUMO

Atrial fibrillation is a common cardiac disease of aging. The risk of stroke and bad prognosis increase with age and atrial fibrillation. Compared with younger people, elderly people have higher risks for both thrombosis and bleeding. Stroke prevention with oral anticoagulants is the cornerstone of the management of atrial fibrillation but is often questioned because of the risk of bleeding, furthermore comorbidities, comedications, fall risks, poor compliance. These factors frequently found in frail elderly patients complicate the management of antithrombotic therapy. This article reviews the evidence for the risks and benefits of anticoagulation in the elderly with atrial fibrillation, by comparing the new oral anticoagulants to vitamin K antagonists.


Assuntos
Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Fibrilação Atrial , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Idoso , Fibrinolíticos , Humanos , Medição de Risco , Fatores de Risco , Vitamina K/antagonistas & inibidores
3.
Emerg Med Clin North Am ; 38(4): 871-889, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32981623

RESUMO

Massive gastrointestinal hemorrhage is a life-threatening condition that can result from numerous causes and requires skilled resuscitation to decrease patient morbidity and mortality. Successful resuscitation begins with placement of large-bore intravenous or intraosseous access; early blood product administration; and early consultation with a gastroenterologist, interventional radiologist, and/or surgeon. Activate a massive transfusion protocol when initial red blood cell transfusion does not restore effective perfusion or the patient's shock index is greater than 1.0. Promptly reverse coagulopathies secondary to oral anticoagulant or antiplatelet use. Use thromboelastography or rotational thromboelastometry to guide further transfusions. Secure a definitive airway and minimize aspiration.


Assuntos
Hemorragia Gastrointestinal/terapia , Manuseio das Vias Aéreas , Antibacterianos/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticoagulantes/efeitos adversos , Antifibrinolíticos/uso terapêutico , Oclusão com Balão , Fatores de Coagulação Sanguínea/administração & dosagem , Transfusão de Sangue/métodos , Cateteres , Serviço Hospitalar de Emergência , Fator Xa/administração & dosagem , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Humanos , Infusões Intraósseas , Infusões Intravenosas , Anamnese , Exame Físico , Inibidores da Bomba de Prótons/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Ressuscitação , Tromboelastografia , Vasoconstritores/uso terapêutico
5.
Int Heart J ; 61(5): 865-871, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32921667

RESUMO

Bleeding complication has been considered as a serious problem in current percutaneous coronary interventions (PCI). Fortunately, several groups have already reported the effectiveness of protamine use just after PCI to immediately remove any arterial sheath. However, there is a concern that protamine reversal may increase non-occlusive thrombus and, in turn, lead to mid-term cardiovascular events such as target vessel revascularization (TVR) or stent thrombosis. Thus, the purpose of this study was to evaluate whether protamine use following elective PCI was associated with mid-term clinical outcomes. In total, 472 patients were included in this study; subsequently, they were divided into protamine group (n = 142) and non-protamine group (n = 330). The primary endpoint was the composite of ischemia-driven TVR and stent thrombosis. The median follow-up period was determined to be at 562 days. In total, 32 primary endpoints were observed during the study period, and the incidence of primary endpoints tended to be greater in the protamine group than in the non-protamine group (P = 0.056). However, the lesion length, the degree of calcification, and the prevalence of hemodialysis were significantly determined greater in the protamine group than in the non-protamine group. In the multivariate Cox proportional hazards model, the use of protamine (versus non-protamine: hazard ratio 0.542 and 95% confidence interval 0.217-1.355, P = 0.191) was deemed not to be associated with the primary endpoint after controlling legion length, calcification, and hemodialysis. In conclusion, immediate protamine use following elective PCI did not increase mid-term ischemia-driven TVR or stent thrombosis. However, immediate protamine use after PCI should be discussed further for the safety of the patient.


Assuntos
Estenose Coronária/cirurgia , Antagonistas de Heparina/uso terapêutico , Intervenção Coronária Percutânea/métodos , Complicações Pós-Operatórias/epidemiologia , Hemorragia Pós-Operatória/prevenção & controle , Protaminas/uso terapêutico , Trombose/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Estudos de Casos e Controles , Estenose Coronária/epidemiologia , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Heparina/efeitos adversos , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Revascularização Miocárdica/estatística & dados numéricos , Complicações Pós-Operatórias/induzido quimicamente , Hemorragia Pós-Operatória/induzido quimicamente , Modelos de Riscos Proporcionais , Diálise Renal , Estudos Retrospectivos , Stents , Trombose/induzido quimicamente , Calcificação Vascular/epidemiologia
6.
An Sist Sanit Navar ; 43(2): 251-254, 2020 Aug 31.
Artigo em Espanhol | MEDLINE | ID: mdl-32865189

RESUMO

Infection caused by SARS-CoV-2 (COVID-19) is associated with an increased risk of thromboembolic disease. So-me authors recommend anticoagulation at therapeutic doses for, at least, the most severely ill patients; this practice is not free of risks, which is why only thromboembolic prophylaxis is recommended by other consensuses. In the case of previously anticoagulated patients, changing the oral anticoagulant for a low molecular weight heparin (LMWH) is generally recommended. We present the cases of two patients admitted due to COVID-19, without serious clinical data, in whom anticoagulation (acenocoumarol and rivaroxaban, respectively) was replaced by LMWH at therapeutic doses, both presenting abdominal bleeding. This type of bleeding is an infrequent complication in anticoagulated patients, but the concurrence of two cases in a short period of time in the context of the COVID-19 pandemic leads us to consider that there is not yet any clear evidence on therapeutic anticoagulation in SARS-CoV-2 infection.


Assuntos
Anticoagulantes/efeitos adversos , Betacoronavirus , Infecções por Coronavirus/complicações , Hematoma/induzido quimicamente , Pneumonia Viral/complicações , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/virologia , Abdome , Acenocumarol/efeitos adversos , Acenocumarol/uso terapêutico , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Feminino , Hematoma/diagnóstico , Heparina de Baixo Peso Molecular/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Pandemias , Rivaroxabana/efeitos adversos , Rivaroxabana/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico
7.
Medicine (Baltimore) ; 99(36): e22028, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899057

RESUMO

Comparison of different anticoagulants in blood management and complications with tranexamic acid (TXA) in total hip arthroplasty (THA) is unclear. Our aim was to compare the efficacy and safety among receiving nadroparin calcium, enoxaparin sodium or rivaroxaban after TXA in THA.150 patients undergoing primary unilateral THA were received 15 mg/kg intravenous TXA (IV-TXA) before skin incision, followed by 1 of nadroparin calcium (Group A), enoxaparin sodium (Group B), or rivaroxaban (Group C) randomly during hospitalization. The primary outcome was hidden blood loss (HBL). Other outcomes such as the maximum hemoglobin (Hb) drop, total blood loss (TBL), the volume of drainage, transfusion rate, length of hospital stay (LOS), and complications were also compared.There were no statistically significant differences in HBL, the maximum hemoglobin (Hb) drop, transfusion rate, and complications among 3 groups. LOS was significantly higher for patients in Group B than Group A (P = .026). Neither deep venous thrombosis (DVT) nor pulmonary embolism (PE) occurred in any group.There were no differences in efficacy and safety in patients undergoing THA receiving nadroparin calcium, enoxaparin sodium, or rivaroxaban after anti-fibrinolysis with TXA.


Assuntos
Anticoagulantes/efeitos adversos , Antifibrinolíticos/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Ácido Tranexâmico/efeitos adversos , Administração Intravenosa , Idoso , Anticoagulantes/administração & dosagem , Antifibrinolíticos/administração & dosagem , Artroplastia de Quadril/efeitos adversos , Transfusão de Sangue/estatística & dados numéricos , China/epidemiologia , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Feminino , Hemoglobinas/análise , Hospitalização , Humanos , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Nadroparina/administração & dosagem , Nadroparina/efeitos adversos , Sangue Oculto , Estudos Retrospectivos , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Segurança , Ácido Tranexâmico/administração & dosagem , Resultado do Tratamento
8.
Trials ; 21(1): 770, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907635

RESUMO

OBJECTIVES: The OVID study will demonstrate whether prophylactic-dose enoxaparin improves survival and reduces hospitalizations in symptomatic ambulatory patients aged 50 or older diagnosed with COVID-19, a novel viral disease characterized by severe systemic, pulmonary, and vessel inflammation and coagulation activation. TRIAL DESIGN: The OVID study is conducted as a multicentre open-label superiority randomised controlled trial. PARTICIPANTS: Inclusion Criteria 1. Signed patient informed consent after being fully informed about the study's background. 2. Patients aged 50 years or older with a positive test for SARS-CoV2 in the past 5 days and eligible for ambulatory treatment. 3. Presence of respiratory symptoms (i.e. cough, sore throat, or shortness of breath) or body temperature >37.5° C. 4. Ability of the patient to travel to the study centre by private transportation, performed either by an accompanying person from the same household or by the patient themselves 5. Ability to comply with standard hygiene requirements at the time of in-hospital visit, including a face mask and hand disinfectant. 6. Ability to walk from car to study centre or reach it by wheelchair transport with the help of an accompanying person from the same household also complying with standard hygiene requirements. 7. Ability to self-administer prefilled enoxaparin injections after instructions received at the study centre or availability of a person living with the patient to administer enoxaparin. Exclusion Criteria 1. Any acute or chronic condition posing an indication for anticoagulant treatment, e.g. atrial fibrillation, prior venous thromboembolism (VTE), acute confirmed symptomatic VTE, acute coronary syndrome. 2. Anticoagulant thromboprophylaxis deemed necessary in view of the patient's history, comorbidity or predisposing strong risk factors for thrombosis: a. Any of the following events occurring in the prior 30 days: fracture of lower limb, hospitalization for heart failure, hip/knee replacement, major trauma, spinal cord injury, stroke, b. previous VTE, c. histologically confirmed malignancy, which was diagnosed or treated (surgery, chemotherapy, radiotherapy) in the past 6 months, or recurrent, or metastatic, or inoperable. 3. Any clinically relevant bleeding (defined as bleeding requiring hospitalization, transfusion, surgical intervention, invasive procedures, occurring in a critical anatomical site, or causing disability) within 30 days prior to randomization or sign of acute bleeding. 4. Intracerebral bleeding at any time in the past or signs/symptoms consistent with acute intracranial haemorrhage. 5. Haemoglobin <8 g/dL and platelet count <50 x 109 cells/L confirmed by recent laboratory test (<90 days). 6. Subjects with any known coagulopathy or bleeding diathesis, including known significant liver disease associated with coagulopathy. 7. Severe renal insufficiency (baseline creatinine clearance <30 mL/min calculated using the Cockcroft-Gault formula) confirmed by recent laboratory test (<90 days). 8. Contraindications to enoxaparin therapy, including prior heparin-induced thrombocytopenia and known hypersensitivity. 9. Current use of dual antiplatelet therapy. 10. Participation in other interventional studies over the past 30 days. 11. Non-compliance or inability to adhere to treatment or lack of a family environment or support system for home treatment. 12. Cognitive impairment and/or inability to understand information provided in the study information. Patient enrolment will take place at seven Swiss centres, including five university hospitals and two large cantonal hospitals. INTERVENTION AND COMPARATOR: Patients randomized to the intervention group will receive subcutaneous enoxaparin at the recommended dose of 4,000 IU anti-Xa activity (40 mg/0.4 ml) once daily for 14 days. Patients randomized to the comparator group will receive no anticoagulation. MAIN OUTCOMES: Primary outcome: a composite of any hospitalization or all-cause death occurring within 30 days of randomization. SECONDARY OUTCOMES: (i) a composite of cardiovascular events, including deep vein thrombosis (including catheter-associated), pulmonary embolism, myocardial infarction/myocarditis, arterial ischemia including mesenteric and extremities, acute splanchnic vein thrombosis, or ischemic stroke within 14 days, 30 days, and 90 days of randomization; (ii) each component of the primary efficacy outcome, within 14 days, 30 days, and 90 days of randomization; (iii) net clinical benefit (accounting for the primary efficacy outcome, composite cardiovascular events, and major bleeding), within 14 days, 30 days, and 90 days of enrolment; (iv) primary efficacy outcome, within 14 days, and 90 days of enrolment; (v) disseminated intravascular coagulation (ISTH criteria, in-hospital diagnosis) within 14 days, 30 days, and 90 days of enrolment. RANDOMISATION: Patients will undergo block stratified randomization (by age: 50-70 vs. >70 years; and by study centre) with a randomization ratio of 1:1 with block sizes varying between 4 and 8. Randomization will be performed after the signature of the informed consent for participation and the verification of the eligibility criteria using the electronic data capture software (REDCAP, Vanderbilt University, v9.1.24). BLINDING (MASKING): In this open-label study, no blinding procedures will be used. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size calculation is based on the parameters α = 0.05 (2-sided), power: 1-ß = 0.8, event rate in experimental group, pexp = 0.09 and event rate in control group, pcon = 0.15. The resulting total sample size is 920. To account for potential dropouts, the total sample size was fixed to 1000 with 500 patients in the intervention group and 500 in the control group. TRIAL STATUS: Protocol version 1.0, 14 April 2020. Protocol version 3.0, 18 May 2020 Recruiting start date: June 2020. Last Patient Last Visit: March 2021. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04400799 First Posted: May 26, 2020 Last Update Posted: July 16, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). 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
Anticoagulantes/administração & dosagem , Betacoronavirus/patogenicidade , Coagulação Sanguínea/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Enoxaparina/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Trombose/prevenção & controle , Anticoagulantes/efeitos adversos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Enoxaparina/efeitos adversos , Estudos de Equivalência como Asunto , Interações Hospedeiro-Patógeno , Humanos , Estudos Multicêntricos como Assunto , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Trombose/sangue , Trombose/diagnóstico , Trombose/virologia , Fatores de Tempo , Resultado do Tratamento
9.
Crit Rev Oncol Hematol ; 154: 103074, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32911455

RESUMO

Novel Oral Anticoagulants (NOACs) have been considered for treating cancer-related venous thromboembolism (VTE), but safety issues have been raised. We performed a systematic review and pairwise meta-analysis of the efficacy and safety of NOACs versus low molecular weight heparin (LMWH) in this setting. Four randomized controlled trials were included, providing data on 2894 patients. Compared to LMWH, NOACs were associated with a significantly lower risk of VTE recurrence and were not associated with an increased risk of major bleedings (MB). NOACs were non inferior to LMWH for a composite outcome of VTE recurrence and MB, pulmonary embolism recurrence and all-cause mortality; however, NOACs were associated with an increased risk of clinically relevant nonmajor bleedings (CRNMB) and gastrointestinal MB. In conclusion, in patients with cancer-related VTE, NOACs are effective and safe in reducing VTE recurrence compared to LMWH. An increased risk of CNRMB and GI MB should nonetheless be considered.


Assuntos
Neoplasias/complicações , Neoplasias/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia , Administração Oral , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Heparina de Baixo Peso Molecular/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos
11.
PLoS One ; 15(8): e0238233, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32866192

RESUMO

OBJECTIVE: To identify risk factors for bleeding in atrial fibrillation (AF) patients treated with anti-coagulants such as warfarin, apixaban, edoxaban, dabigatran, rivaroxaban using a large claims database. METHODS: A claims database for 8926 AF patients from 2004 to 2016 was obtained from JMDC. Inc. We performed a retrospective cohort study in 2796 Japanese AF patients with 4-month screening and 12-month observation periods. Polypharmacy was defined as prescription of over six drugs. Logistic regression analysis was conducted after stratification based on the presence and absence of cerebrovascular diseases to detect the predictive factors for bleeding. RESULTS: Polypharmacy was observed in 815 of 2796 (29.1%) patients. A total of 371 AF patients (13.3%) experienced bleeding in the 12-month observation period. Bleeding risk assessment using multiple logistic regression analysis revealed that the odds ratio for the number of co-administered drugs in the elderly (age for ≥60, ≤74) was not significant in those without and with cerebrovascular diseases (1.05 [0.99-1.12], N.S. and 1.10 [0.96-1.27], N.S.). In contrast, in the young (age for <60), the number of co-administered drugs was a significant predictive factor in those without and with cerebrovascular diseases (1.09 [1.03-1.16], p = 0.0054 and 1.20 [1.05-1.36], p = 0.0059). Other observed predictors were"history of bleeding" in young and elderly, but "polypharmacy" and "start from warfarin" were observed in only young. CONCLUSION: We determined the bleeding risk in the clinical setting using a large claims database. Physicians and pharmacists need to monitor patients for the initial bleeding signs, particularly in those with these predictive risk factors.


Assuntos
Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Hemorragia/induzido quimicamente , Gerenciamento de Dados/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco
12.
J Clin Pharmacol ; 60(11): 1411-1415, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32885463

RESUMO

The pathophysiology of respiratory failure associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains under investigation. One hypothesis is that progressive endothelial damage from the virus leads to microvascular thrombosis. It is uncertain if empiric therapeutic anticoagulation provides benefit over standard deep vein thrombosis (DVT) prophylaxis in critically ill patients with SARS-CoV-2. A retrospective cohort study was performed to evaluate adult patients admitted to the intensive care unit at 3 hospitals with polymerase chain reaction-confirmed SARS-CoV-2-associated respiratory failure requiring invasive mechanical ventilation. A Kaplan-Meier survival analysis was used to compare patients who were initiated on therapeutic anticoagulation prior to the time of intubation and those receiving standard DVT prophylaxis doses. The primary outcome was the difference in the 28-day mortality of patients between the 2 groups. Twenty-eight-day mortality did not differ between groups, occurring in 26.1% of patients who received therapeutic anticoagulation and 29.5% of those who received a prophylactic dose only (hazard ratio, 0.52; P = .055). There was no difference in 28-day mortality between groups in patients who were admitted with a serum D-dimer ≥ 2 µg/mL (hazard ratio, 0.67; P = .41). Empiric therapeutic anticoagulation in patients who require invasive mechanical ventilation for confirmed SARS-CoV-2 infection does not improve 28-day mortality compared with standard DVT prophylaxis, even among those with elevated D-dimer levels.


Assuntos
Anticoagulantes/uso terapêutico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Estado Terminal/mortalidade , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/mortalidade , Idoso , Anticoagulantes/efeitos adversos , Estudos de Coortes , Infecções por Coronavirus/tratamento farmacológico , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/tratamento farmacológico , Respiração Artificial , Insuficiência Respiratória/tratamento farmacológico , Estudos Retrospectivos , Análise de Sobrevida
13.
Lancet Haematol ; 7(10): e746-e755, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32976752

RESUMO

BACKGROUND: Study-level meta-analyses provide high-certainty evidence that heparin reduces the risk of symptomatic venous thromboembolism for patients with cancer; however, whether the benefits and harms associated with heparin differ by cancer type is unclear. This individual participant data meta-analysis of randomised controlled trials examines the effect of heparin on survival, venous thromboembolism, and bleeding in patients with cancer in general and by type. METHODS: In this systematic review and meta-analysis we searched MEDLINE, Embase, and The Cochrane Library for randomised controlled trials comparing parenteral anticoagulants with placebo or standard care in ambulatory patients with solid tumours and no indication for anticoagulation published from the inception of each database to January 14, 2017, and updated it on May 14, 2020, without language restrictions. We calculated the effect of parenteral anticoagulant administration on all-cause mortality, venous thromboembolism occurrence, and bleeding related outcomes through multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect, adjusting for age, cancer type, and metastatic status. Interaction terms were tested to investigate effects in predefined subgroups. This study is registered with PROSPERO, CRD42013003526. FINDINGS: We obtained individual participant data from 14 of 20 eligible randomised controlled trials (8278 [79%] of 10 431 participants; 4139 included in the low-molecular-weight heparin group and 4139 in the control group). Meta-analysis showed an adjusted relative risk (RR) of mortality at 1 year of 0·99 (95% CI 0·93-1·06) and a hazard ratio of 1·01 (95% CI 0·96-1·07). The number of patients with venous thromboembolic events was 158 (4·0%) of 3958 with available data in the low-molecular-weight heparin group compared with 279 (7·1%) of 3957 in the control group. Major bleeding events occurred in 71 (1·7%) of 4139 patients in the control population and 88 (2·1%) in the low-molecular-weight heparin group, and minor bleeding events in 478 (12·1%) of 3945 patients with available data in the control group and 652 (16·6%) of 3937 patients in the low-molecular-weight heparin group. The adjusted RR was 0·58 (95% CI 0·47-0·71) for venous thromboembolism, 1·27 (0·92-1·74) for major bleeding, and 1·34 (1·19-1·51) for minor bleeding. Prespecified subgroup analysis of venous thromboembolism occurrence by cancer type identified the most certain benefit from heparin treatment in patients with lung cancer (RR 0·59 [95% CI 0·42-0·81]), which dominated the overall reduction in venous thromboembolism. Certainty of the evidence for the outcomes ranged from moderate to high. INTERPRETATION: Low-molecular-weight heparin reduces risk of venous thromboembolism without increasing risk of major bleeding compared with placebo or standard care in patients with solid tumours, but it does not improve survival. FUNDING: Canadian Institutes of Health Research.


Assuntos
Anticoagulantes/uso terapêutico , Heparina/uso terapêutico , Neoplasias/complicações , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Heparina de Baixo Peso Molecular/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Análise de Sobrevida
14.
BMJ ; 370: m2177, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32759284

RESUMO

Pulmonary embolism is a common and potentially fatal cardiovascular disorder that must be promptly diagnosed and treated. The diagnosis, risk assessment, and management of pulmonary embolism have evolved with a better understanding of efficient use of diagnostic and therapeutic options. The use of either clinical probability adjusted or age adjusted D-dimer interpretation has led to a reduction in diagnostic imaging to exclude pulmonary embolism. Direct oral anticoagulation therapies are safe, effective, and convenient treatments for most patients with acute venous thromboembolism, with a lower risk of bleeding than vitamin K antagonists. These oral therapeutic options have opened up opportunities for safe outpatient management of pulmonary embolism in selected patients. Recent clinical trials exploring the use of systemic thrombolysis in intermediate to high risk pulmonary embolism suggest that this therapy should be reserved for patients with evidence of hemodynamic compromise. The role of low dose systemic or catheter directed thrombolysis in other patient subgroups is uncertain. After a diagnosis of pulmonary embolism, all patients should be assessed for risk of recurrent venous thromboembolism to guide duration of anticoagulation. Patients with a venous thromboembolism associated with a strong, transient, provoking risk factor can safely discontinue anticoagulation after three months of treatment. Patients with an ongoing strong risk factor, such as cancer, or unprovoked events are at increased risk of recurrent events and should be considered for extended treatment. The use of a risk prediction score can help to identify patients with unprovoked venous thromboembolism who can benefit from extended duration therapy. Despite major advances in the management of pulmonary embolism, up to half of patients report chronic functional limitations. Such patients should be screened for chronic thromboembolic pulmonary hypertension, but only a small proportion will have this as the explanation of their symptoms. In the remaining patients, future studies are needed to understand the pathophysiology and explore interventions to improve quality of life.


Assuntos
Anticoagulantes/uso terapêutico , Neoplasias/complicações , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/terapia , Administração Oral , Anticoagulantes/efeitos adversos , Angiografia por Tomografia Computadorizada , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinolíticos/uso terapêutico , Humanos , Imagem de Perfusão , Gravidez , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/etiologia , Recidiva , Medição de Risco , Fatores de Risco , Filtros de Veia Cava , Tromboembolia Venosa/tratamento farmacológico
15.
PLoS One ; 15(8): e0235628, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32745092

RESUMO

BACKGROUND: Emerging evidence suggests aspirin may be an effective venous thromboembolism (VTE) prophylaxis for orthopaedic trauma patients, with fewer bleeding complications. We used a patient-centered weighted composite outcome to globally evaluate aspirin versus low-molecular-weight heparin (LMWH) for VTE prevention in fracture patients. METHODS: We conducted an open-label randomized clinical trial of adult patients admitted to an academic trauma center with an operative extremity fracture, or a pelvis or acetabular fracture. Patients were randomized to receive LMWH (enoxaparin 30-mg) twice daily (n = 164) or aspirin 81-mg twice daily (n = 165). The primary outcome was a composite endpoint of bleeding complications, deep surgical site infection, deep vein thrombosis, pulmonary embolism, and death within 90 days of injury. A Global Rank test and weighted time to event analysis were used to determine the probability of treatment superiority for LMWH, given a 9% patient preference margin for oral administration over skin injections. RESULTS: Overall, 18 different combinations of outcomes were experienced by patients in the study. Ninety-nine patients in the aspirin group (59.9%) and 98 patients in the LMWH group (59.4%) were event-free within 90 days of injury. Using a Global Rank test, the LMWH had a 50.4% (95% CI, 47.7-53.2%, p = 0.73) probability of treatment superiority over aspirin. In the time to event analysis, LMWH had a 60.5% probability of treatment superiority over aspirin with considerable uncertainty (95% CI, 24.3-88.0%, p = 0.59). CONCLUSION: The findings of the Global Rank test suggest no evidence of superiority between LMWH or aspirin for VTE prevention in fracture patients. LMWH demonstrated a 60.5% VTE prevention benefit in the weighted time to event analysis. However, this difference did not reach statistical significance and was similar to the elicited patient preferences for aspirin.


Assuntos
Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Enoxaparina/uso terapêutico , Fibrinolíticos/uso terapêutico , Fraturas Ósseas/complicações , Tromboembolia Venosa/prevenção & controle , Adulto , Idoso , Anticoagulantes/efeitos adversos , Aspirina/efeitos adversos , Enoxaparina/efeitos adversos , Feminino , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Tromboembolia Venosa/complicações , Adulto Jovem
16.
Am J Gastroenterol ; 115(10): 1609-1616, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32796176

RESUMO

INTRODUCTION: Although current literature has addressed gastrointestinal presentations including nausea, vomiting, diarrhea, abnormal liver chemistries, and hyperlipasemia as possible coronavirus disease 2019 (COVID-19) manifestations, the risk and type of gastrointestinal bleeding (GIB) in this population is not well characterized. METHODS: This is a matched case-control (1:2) study with 41 cases of GIB (31 upper and 10 lower) in patients with COVID-19 and 82 matched controls of patients with COVID-19 without GIB. The primary objective was to characterize bleeding etiologies, and our secondary aim was to discuss outcomes and therapeutic approaches. RESULTS: There was no difference in the presenting symptoms of the cases and controls, and no difference in severity of COVID-19 manifestations (P > 0.05) was observed. Ten (32%) patients with upper GIB underwent esophagogastroduodenoscopy and 5 (50%) patients with lower GIBs underwent flexible sigmoidoscopy or colonoscopy. The most common upper and lower GIB etiologies were gastric or duodenal ulcers (80%) and rectal ulcers related to rectal tubes (60%), respectively. Four of the esophagogastroduodenoscopies resulted in therapeutic interventions, and the 3 patients with rectal ulcers were referred to colorectal surgery for rectal packing. Successful hemostasis was achieved in all 7 cases that required interventions. Transfusion requirements between patients who underwent endoscopic therapy and those who were conservatively managed were not significantly different. Anticoagulation and rectal tube usage trended toward being a risk factor for GIB, although it did not reach statistical significance. DISCUSSION: In COVID-19 patients with GIB, compared with matched controls of COVID-19 patients without GIB, there seemed to be no difference in initial presenting symptoms. Of those with upper and lower GIB, the most common etiology was peptic ulcer disease and rectal ulcers from rectal tubes, respectively. Conservative management seems to be a reasonable initial approach in managing these complex cases, but larger studies are needed to guide management.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Hemorragia Gastrointestinal/epidemiologia , Úlcera Péptica/epidemiologia , Pneumonia Viral/complicações , Doenças Retais/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Transfusão de Sangue/estatística & dados numéricos , Estudos de Casos e Controles , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Endoscopia/estatística & dados numéricos , Enema/efeitos adversos , Enema/instrumentação , Feminino , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Técnicas Hemostáticas/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Úlcera Péptica/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Doenças Retais/etiologia , Doenças Retais/terapia , Fatores de Risco
17.
J Cardiothorac Vasc Anesth ; 34(11): 3006-3012, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32828653

RESUMO

OBJECTIVE: Anticoagulation may be a challenge in coronavirus disease 2019 (COVID-19) extracorporeal membrane oxygenation due to endothelial injury and dysregulation of coagulation, which may increase the risk of thrombotic and bleeding complications. This report was created to describe the authors' single institutional experience, with emphasis on the high rate of intracranial hemorrhage for the first 10 patients with COVID-19 placed on venovenous extracorporeal membrane oxygenation (VV ECMO). DESIGN: Case series, retrospective analysis. SETTING: Single institution. PARTICIPANTS: Ten patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, mortality, stroke rate, and length of stay data were collected in all patients. In addition, laboratory values of D-dimer and C-reactive protein and standard measurements of prothrombin and activated partial thromboplastin time were collected on all patients. Ten patients, each confirmed with COVID-19 via reverse transcription-polymerase chain reaction, were supported on VV ECMO for acute respiratory distress syndrome (ARDS) for a mean duration of 9.4 ± 7 days. Four of 10 patients had hemorrhagic strokes, 3 of which resulted in death. At 30 days after initiation of VV ECMO, a total of 7 survivors included 6 patients discharged from the hospital and 1 patient who remained in the intensive care unit. CONCLUSIONS: In this small study of 10 patients, intracranial hemorrhage was a common complication, resulting in a high rate of death. The authors urge caution in the anticoagulation management of VV ECMO for patients with severe ARDS and COVID-19 patients. Close monitoring of all hematologic parameters is recommended during ECMO support while awaiting larger, multicenter studies to examine the best practice.


Assuntos
Anticoagulantes/administração & dosagem , Betacoronavirus , Infecções por Coronavirus/terapia , Oxigenação por Membrana Extracorpórea/efeitos adversos , Hemorragias Intracranianas/etiologia , Pneumonia Viral/terapia , Anticoagulantes/efeitos adversos , Infecções por Coronavirus/epidemiologia , Oxigenação por Membrana Extracorpórea/métodos , Feminino , Seguimentos , Humanos , Hemorragias Intracranianas/diagnóstico , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Estudos Retrospectivos
18.
J Investig Med High Impact Case Rep ; 8: 2324709620944091, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32720827

RESUMO

COVID-19 (coronavirus disease-2019) infection is a highly prothrombotic state, resulting from a dysregulation of the coagulation cascade. Therefore, thromboprophylaxis is strongly recommended in these patients, with some experts even advocating for therapeutic dosing to prevent thromboembolic events. Heparin-induced thrombocytopenia (HIT) is a well-known complication of heparin therapy. In this article, we report a case of HIT in a patient with COVID-19. A 63-year-old male presented with 1 week of dry cough and diarrhea. He had a positive nasopharyngeal COVID-19 reverse-transcriptase-polymerase chain reaction. On admission, the platelet count and liver function tests were within normal limits. During his hospitalization, he developed a right femoral deep venous thrombosis and was started on therapeutic anticoagulation. Due to worsening respiratory failure, he was intubated and mechanically ventilated. Between days 11 and 12 of hospitalization, platelet count dropped from 304 000 to 96 000 cells/µL. He had a high pretest probability for HIT with a 4T score of 6 and a positive anti-PF4/heparin antibody. Heparin drip was discontinued and was switched to argatroban. The serotonin release assay eventually returned positive, which confirmed the diagnosis of HIT. We also discuss potential overdiagnosis of HIT in COVID-19 through 4 cases with false-positive HIT antibodies.


Assuntos
Anticoagulantes/efeitos adversos , Infecções por Coronavirus/complicações , Heparina/efeitos adversos , Pneumonia Viral/complicações , Trombocitopenia/induzido quimicamente , Trombose Venosa/tratamento farmacológico , Trombose Venosa/etiologia , Betacoronavirus , Humanos , Perna (Membro)/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Pandemias
20.
J Stroke Cerebrovasc Dis ; 29(8): 104984, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32689588

RESUMO

BACKGROUND AND PURPOSE: Patients with the Coronavirus Disease of 2019 (COVID-19) are at increased risk for thrombotic events and mortality. Various anticoagulation regimens are now being considered for these patients. Anticoagulation is known to increase the risk for adverse bleeding events, of which intracranial hemorrhage (ICH) is one of the most feared. We present a retrospective study of 33 patients positive for COVID-19 with neuroimaging-documented ICH and examine anticoagulation use in this population. METHODS: Patients over the age of 18 with confirmed COVID-19 and radiographic evidence of ICH were included in this study. Evidence of hemorrhage was confirmed and categorized by a fellowship trained neuroradiologist. Electronic health records were analyzed for patient information including demographic data, medical history, hospital course, laboratory values, and medications. RESULTS: We identified 33 COVID-19 positive patients with ICH, mean age 61.6 years (range 37-83 years), 21.2% of whom were female. Parenchymal hemorrhages with mass effect and herniation occurred in 5 (15.2%) patients, with a 100% mortality rate. Of the remaining 28 patients with ICH, 7 (25%) had punctate hemorrhages, 17 (60.7%) had small- moderate size hemorrhages, and 4 (14.3%) had a large single site of hemorrhage without evidence of herniation. Almost all patients received either therapeutic dose anticoagulation (in 22 [66.7%] patients) or prophylactic dose (in 3 [9.1] patients) prior to ICH discovery. CONCLUSIONS: Anticoagulation therapy may be considered in patients with COVID-19 though the risk of ICH should be taken into account when developing a treatment regimen.


Assuntos
Anticoagulantes/efeitos adversos , Betacoronavirus/patogenicidade , Coagulação Sanguínea/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Hemorragias Intracranianas/induzido quimicamente , Pneumonia Viral/tratamento farmacológico , Acidente Vascular Cerebral/induzido quimicamente , Trombose/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Feminino , Interações entre Hospedeiro e Microrganismos , Humanos , Hemorragias Intracranianas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagem , Trombose/sangue , Trombose/diagnóstico , Trombose/virologia , Fatores de Tempo , Resultado do Tratamento
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