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1.
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 , Enoxaparina/administração & dosagem , Oxigenação por Membrana Extracorpórea , Oxigenoterapia/métodos , Trombose/prevenção & controle , Idoso , Anticoagulantes/efeitos adversos , 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
2.
J Thromb Thrombolysis ; 51(3): 595-607, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33586113

RESUMO

A prothrombotic state is reported with severe COVID-19 infection, which can manifest in venous and arterial thrombotic events. Coagulopathy is reflective of more severe disease and anticoagulant thromboprophylaxis is recommended in hospitalized patients. However, the prevalence of thrombosis on the intensive care unit (ICU) remains unclear, including whether this is sufficiently addressed by conventional anticoagulant thromboprophylaxis. We aimed to identify the rate of thrombotic complications in ICU-treated patients with COVID-19, to inform recommendations for diagnosis and management. A systematic review was conducted to assess the incidence of thrombotic complications in ICU-treated patients with COVID-19. Observational studies and registries reporting thrombotic complications in ICU-treated patients were included. Information extracted included patient demographics, use of thromboprophylaxis or anticoagulation, method of identifying thrombotic complications, and reported patient outcomes. In 28 studies including 2928 patients, thrombotic complications occurred in 34% of ICU-managed patients, with deep venous thrombosis reported in 16.1% and pulmonary embolism in 12.6% of patients, despite anticoagulant thromboprophylaxis, and were associated with high mortality. Studies adopting systematic screening for venous thrombosis with Duplex ultrasound reported a significantly higher incidence of venous thrombosis compared to those relying on clinical suspicion (56.3% vs. 11.0%, p < 0.001). Despite thromboprophylaxis, there is a very high incidence of thrombotic complications in patients with COVID-19 on the ICU. Systematic screening identifies many thrombotic complications that would be missed by relying on clinical suspicion and should be employed, with consideration given to increased dose anticoagulant thromboprophylaxis, whilst awaiting results of prospective trials of anticoagulation in this cohort.


Assuntos
/complicações , Trombose/mortalidade , Trombose/virologia , Anticoagulantes/uso terapêutico , Oxigenação por Membrana Extracorpórea , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Trombose/prevenção & controle
3.
Am Heart J ; 235: 12-23, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33577800

RESUMO

BACKGROUND: COVID-19 is associated with both venous and arterial thrombotic complications. While prophylactic anticoagulation is now widely recommended for hospitalized patients with COVID-19, the effectiveness and safety of thromboprophylaxis in outpatients with COVID-19 has not been established. STUDY DESIGN: PREVENT-HD is a double-blind, placebo-controlled, pragmatic, event-driven phase 3 trial to evaluate the efficacy and safety of rivaroxaban in symptomatic outpatients with laboratory-confirmed COVID-19 at risk for thrombotic events, hospitalization, and death. Several challenges posed by the pandemic have necessitated innovative approaches to clinical trial design, start-up, and conduct. Participants are randomized in a 1:1 ratio, stratified by time from COVID-19 confirmation, to either rivaroxaban 10 mg once daily or placebo for 35 days. The primary efficacy end point is a composite of symptomatic venous thromboembolism, myocardial infarction, ischemic stroke, acute limb ischemia, non-central nervous system systemic embolization, all-cause hospitalization, and all-cause mortality. The primary safety end point is fatal and critical site bleeding according to the International Society on Thrombosis and Haemostasis definition. Enrollment began in August 2020 and is expected to enroll approximately 4,000 participants to yield the required number of end point events. CONCLUSIONS: PREVENT-HD is a pragmatic trial evaluating the efficacy and safety of the direct oral anticoagulant rivaroxaban in the outpatient setting to reduce major venous and arterial thrombotic events, hospitalization, and mortality associated with COVID-19.


Assuntos
/complicações , Inibidores do Fator Xa/uso terapêutico , Hospitalização , Pacientes Ambulatoriais , Rivaroxabana/uso terapêutico , Trombose/prevenção & controle , Adulto , Causas de Morte , Método Duplo-Cego , Extremidades/irrigação sanguínea , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/mortalidade , Mortalidade Hospitalar , Humanos , Isquemia/etiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Placebos/uso terapêutico , Rivaroxabana/efeitos adversos , Trombose/mortalidade , Tromboembolia Venosa/mortalidade , Tromboembolia Venosa/prevenção & controle
4.
Eur Rev Med Pharmacol Sci ; 25(3): 1684-1707, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33629339

RESUMO

The mortality of COVID-19 patients is increasing in logarithmic fashion and is mostly observed in older age people and patients having history of chronic ailments like chronic obstructive pulmonary disease (COPD), hypertension, diabetes, cardiovascular & cerebrovascular dysfunction, compromised immunity, renal comorbidities, hepatic, obesity problems etc., and recently investigated thrombotic complications. The molecular underpinnings linking the chronic human diseases with COVID-19 related morbidity and mortality are evolving and poorly understood. The aim of the present review is to discuss the mortality and morbidity in COVID-19 in relation to preexisting comorbidities across the globe, upcoming molecular mechanisms associated with expression profile of ACE2 and viral load, evolving pathophysiology of COVID-19 with special reference to thrombotic complication ('Storm of Blood Clots') and related predictive markers. The levels of plasminogen/plasmin in comorbid diseases of COVID-19 have been elaborated in the framework of risk and benefits of fibrinolysis in COVID-19. We have also attempted to discuss the puzzle of prescribing ARBs and ACEI drugs in COVID-19 management which are routinely prescribed for the management of hypertension in COVID-19 patients. A focused discourse on risk of cardiovascular complications and diabetes in concert with COVID-19 pathogenesis has been presented along with dynamics of SARS-CoV-2 induced immune dysfunctions in COVID-19 patients.


Assuntos
/biossíntese , Trombose/mortalidade , /sangue , Comorbidade , Humanos , Morbidade/tendências , Mortalidade/tendências , Glicoproteína da Espícula de Coronavírus/metabolismo , Trombose/sangue , Trombose/etiologia , Carga Viral
5.
Med Clin (Barc) ; 156(3): 112-117, 2021 02 12.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33342556

RESUMO

OBJECTIVE: To analyze the survival of patients hospitalized with covid-19 and who presented some vascular thrombotic complication. MATERIAL AND METHODS: All consecutive patients with covid-19 who were treated during the months of March and April 2020 at our institution were included. All patients were symptomatic and the thrombotic event objectively confirmed. Patients with deep vein thrombosis (DVT), pulmonary embolism (PE), ischemic stroke, and peripheral arterial thrombosis (PAT) were included. Survival curves for all groups were analyzed using Kaplan-Meier with log rank test, and Cox regression. RESULTS: During the pandemic period from March-1 to April-30, 2943 patients were treated with confirmed covid-19 in our center. Of them, 106 patients showed some symptomatic vascular thrombosis: 13 patients had PAT, 15 ischemic stroke, 20 DVT and 58 PE. Another 11 patients presented multiple vascular thrombosis. Although the mean age was 65 years, there were differences between groups being older those patients with arterial thrombosis. A 67.92% were men. In total, 25 patients died during their hospital admission (23.58%), with differences between groups, being more common in patients with PAT (9 patients out of 13) and ischemic stroke (8 patients out of 15), than in those with DVT (1 patient out of 20) or PE (7 patients out of 58). CONCLUSIONS: The venous thromboembolic risk in these patients is greater than the arterial, but arterial thrombosis when it occurs was associated with high mortality rates. Survival was better in patients with DVT and PE than in patients with ischemic stroke or PAT.


Assuntos
/mortalidade , Mortalidade Hospitalar , Embolia Pulmonar/virologia , Acidente Vascular Cerebral/virologia , Trombose/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/mortalidade , Fatores de Risco , Espanha/epidemiologia , Acidente Vascular Cerebral/mortalidade , Análise de Sobrevida , Trombose/mortalidade
8.
Open Heart ; 7(2)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33106441

RESUMO

OBJECTIVES: To understand the impact of COVID-19 on delivery and outcomes of primary percutaneous coronary intervention (PPCI). Furthermore, to compare clinical presentation and outcomes of patients with ST-segment elevation myocardial infarction (STEMI) with active COVID-19 against those without COVID-19. METHODS: We systematically analysed 348 STEMI cases presenting to the PPCI programme in London during the peak of the pandemic (1 March to 30 April 2020) and compared with 440 cases from the same period in 2019. Outcomes of interest included ambulance response times, timeliness of revascularisation, angiographic and procedural characteristics, and in-hospital clinical outcomes RESULTS: There was a 21% reduction in STEMI admissions and longer ambulance response times (87 (62-118) min in 2020 vs 75 (57-95) min in 2019, p<0.001), but that this was not associated with a delays in achieving revascularisation once in hospital (48 (34-65) min in 2020 vs 48 (35-70) min in 2019, p=0.35) or increased mortality (10.9% (38) in 2020 vs 8.6% (38) in 2019, p=0.28). 46 patients with active COVID-19 were more thrombotic and more likely to have intensive care unit admissions (32.6% (15) vs 9.3% (28), OR 5.74 (95%CI 2.24 to 9.89), p<0.001). They also had increased length of stay (4 (3-9) days vs 3 (2-4) days, p<0.001) and a higher mortality (21.7% (10) vs 9.3% (28), OR 2.72 (95% CI 1.25 to 5.82), p=0.012) compared with patients having PPCI without COVID-19. CONCLUSION: These findings suggest that PPCI pathways can be maintained during unprecedented healthcare emergencies but confirms the high mortality of STEMI in the context of concomitant COVID-19 infection characterised by a heightened state of thrombogenicity.


Assuntos
Infecções por Coronavirus , Procedimentos Clínicos/organização & administração , Prestação Integrada de Cuidados de Saúde/organização & administração , Avaliação de Processos e Resultados em Cuidados de Saúde/organização & administração , Pandemias , Intervenção Coronária Percutânea , Pneumonia Viral , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Idoso , Ambulâncias/organização & administração , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Bases de Dados Factuais , Feminino , Mortalidade Hospitalar , Humanos , Tempo de Internação , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Segurança do Paciente , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Pneumonia Viral/transmissão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Trombose/mortalidade , Trombose/terapia , Fatores de Tempo , Tempo para o Tratamento/organização & administração , Resultado do Tratamento
9.
J Int Med Res ; 48(9): 300060520955037, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32960106

RESUMO

BACKGROUND: The roles of inflammation and hypercoagulation in predicting outcomes of coronavirus disease 2019 (COVID-19) are unclear. METHODS: Adult patients diagnosed with COVID-19 from 28 January 2020 to 4 March 2020 in Tongji Hospital, Wuhan were recruited. Data on related parameters were collected. Univariate analysis and multivariable binary logistic regression were used to explore predictors of critical illness and mortality. RESULTS: In total, 199 and 44 patients were enrolled in the training and testing sets, respectively. Elevated ferritin, tumor necrosis factor-α and D-dimer and decreased albumin concentration were associated with disease severity. Older age, elevated ferritin and elevated interleukin-6 were associated with 28-day mortality. The FAD-85 score, defined as age + 0.01 * ferritin +D-dimer, was used to predict risk of mortality. The sensitivity, specificity and accuracy of FAD-85 were 86.4%, 81.8% and 86.4%, respectively. A nomogram was established using age, ferritin and D-dimer to predict the risk of 28-day mortality. CONCLUSIONS: Thrombo-inflammatory parameters provide key information on the severity and prognosis of COVID-19 and can be used as references for clinical treatment to correct inflammatory and coagulation abnormalities.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/mortalidade , Coagulação Intravascular Disseminada/mortalidade , Pneumonia Viral/mortalidade , Trombose/mortalidade , Adulto , Idoso , Biomarcadores/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Coagulação Intravascular Disseminada/complicações , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/virologia , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Interleucina-6/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Prognóstico , Projetos de Pesquisa , Estudos Retrospectivos , Albumina Sérica/metabolismo , Índice de Gravidade de Doença , Análise de Sobrevida , Trombose/complicações , Trombose/diagnóstico , Trombose/virologia , Fator de Necrose Tumoral alfa/sangue
10.
Arterioscler Thromb Vasc Biol ; 40(10): 2404-2407, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32762443

RESUMO

OBJECTIVE: Alveolar-capillary endothelial cells can be activated by severe acute respiratory syndrome coronavirus 2 infection leading to cytokine release. This could trigger endothelial dysfunction, pyroptosis, and thrombosis, which are the vascular changes, commonly referred to as coronavirus disease 2019 (COVID-19) endotheliopathy. Thus, this study aimed to identify tissue biomarkers associated with endothelial activation/dysfunction and the pyroptosis pathway in the lung samples of patients with COVID-19 and to compare them to pandemic influenza A virus H1N1 subtype 2009 and control cases. Approach and Results: Postmortem lung samples (COVID-19 group =6 cases; H1N1 group =10 cases, and control group =11 cases) were analyzed using immunohistochemistry and the following monoclonal primary antibodies: anti-IL (interleukin)-6, anti-TNF (tumor necrosis factor)-α, anti-ICAM-1 (intercellular adhesion molecule 1), and anticaspase-1. From the result, IL-6, TNF-α, ICAM-1, and caspase-1 showed higher tissue expression in the COVID-19 group than in the H1N1 and control groups. CONCLUSIONS: Our results demonstrated endothelial dysfunction and suggested the participation of the pyroptosis pathway in the pulmonary samples. These conditions might lead to systemic thrombotic events that could impair the clinical staff's efforts to avoid fatal outcomes. One of the health professionals' goals should be to identify the high risk of thrombosis patients early to block endotheliopathy and its consequences.


Assuntos
Infecções por Coronavirus/patologia , Células Endoteliais/citologia , Endotélio Vascular/patologia , Pneumonia Viral/patologia , Trombose/patologia , Doenças Vasculares/patologia , Autopsia , Biópsia por Agulha , Causas de Morte , Infecções por Coronavirus/mortalidade , Células Endoteliais/patologia , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pandemias , Pneumonia Viral/mortalidade , Medição de Risco , Trombose/etiologia , Trombose/mortalidade , Doenças Vasculares/mortalidade , Doenças Vasculares/fisiopatologia
12.
Cardiovasc Drugs Ther ; 34(5): 663-675, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32601780

RESUMO

PURPOSE: The ischemic/bleeding trade-off of continuing dual antiplatelet therapy (DAPT) beyond 1 year after PCI for patients with high thrombotic risk (HTR) as endorsed by 2018 ESC/EACTS myocardial revascularization guidelines remain unknown. METHODS: Patients undergoing coronary stenting between January 2013 and December 2013 from the prospective Fuwai registry were defined as HTR if they met at least 1 ESC/EACTS guideline-endorsed HTR criteria. A total of 4578 patients who were at HTR and were events free at 1 year after the index procedure were evaluated. The primary efficacy outcome was major adverse cardiac and cerebrovascular events (MACCE) (composite of all-cause death, myocardial infarction, or stroke). RESULTS: Median follow-up period was 2.4 years. > 1-year DAPT with clopidogrel and aspirin significantly reduced the risk of MACCE compared with ≤ 1-year DAPT (1.9% vs. 4.6%; hazard ratio (HR): 0.38; 95% confidence interval (CI): 0.27-0.54; P < 0.001), driven by a reduction in all-cause death (0.2% vs. 3.0%; HR, 0.07; 95% CI, 0.03-0.15). Cardiac death and definite/probable stent thrombosis also occurred less frequently in prolonged DAPT group. Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding occurred similarly between both groups (1.1% vs. 0.9%; HR, 1.11; 95% CI, 0.58-2.13; P = 0.763). Similar results were found using multivariable Cox model, propensity score-matched, and inverse probability of treatment weighting analysis. CONCLUSIONS: Among patients with ESC-endorsed HTR who were free from major ischemic or bleeding events 1 year after coronary stenting, continued DAPT beyond 1 year might offer better effectiveness in terms of atherothrombotic events and comparable safety in terms of clinically relevant bleeding compared with ≤ 1-year DAPT. ESC-HTR criteria is an important parameter to take into account in tailoring DAPT prolongation.


Assuntos
Doença da Artéria Coronariana/terapia , Terapia Antiplaquetária Dupla , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/administração & dosagem , Trombose/prevenção & controle , Idoso , Pequim , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Esquema de Medicação , Terapia Antiplaquetária Dupla/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Intervalo Livre de Progressão , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Stents , Trombose/etiologia , Trombose/mortalidade , Fatores de Tempo
13.
Cardiovasc Drugs Ther ; 34(5): 659-662, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32488426

RESUMO

BACKGROUND: The prognostic role of procedural complexity when discontinuing aspirin in patients on oral anticoagulation undergoing percutaneous coronary intervention (PCI) has never been studied. METHODS: Ischaemic events were compared in 256 consecutive patients according to procedural complexity and aspirin on discharge. PCI complexity was defined according to the high-risk features for ischaemic events in the current guidelines RESULTS: Forty percent patients had stable presentation. In patients with complex PCI, ischaemic events were significantly higher when discharged without aspirin (adjusted HR 3.66, (95% CI 1.07 to 12.47), P = 0.038). This was driven from both target vessel failure and de-novo coronary lesions. Ischaemic events were comparable between patients with complex PCI on aspirin and those who underwent non-complex PCI. CONCLUSIONS: Procedural complexity in patients with indication for oral anticoagulation undergoing PCI should be factored in when deciding optimal antithrombotic therapies. Aspirin discontinuation in patients with high-risk PCI features should be discouraged.


Assuntos
Anticoagulantes/administração & dosagem , Aspirina/administração & dosagem , Fibrinolíticos/administração & dosagem , Isquemia Miocárdica/terapia , Intervenção Coronária Percutânea , Trombose/prevenção & controle , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Aspirina/efeitos adversos , Esquema de Medicação , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Masculino , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/mortalidade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Fatores de Risco , Trombose/etiologia , Trombose/mortalidade , Fatores de Tempo , Resultado do Tratamento
14.
Int J Hematol ; 112(3): 377-384, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32514928

RESUMO

Chronic kidney disease (CKD) is a well-known risk factor for venous thromboembolism and cardiovascular (CV) disease development in the general population, but its role in thrombotic risk in essential thrombocythemia (ET) and polycythemia vera (PV) remains poorly understood. This retrospective multicenter study analyzed clinical correlations and the potential impact of CKD on thrombosis development in ET and PV patients. We included 167 patients (76 ET and 91 PV); 25.7% had CKD at diagnosis, defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 for ≥ 3 months. Lower eGFR correlated with advanced age, female sex, higher granulocytes, higher serum C-reactive protein, history of thrombosis, CV risk factors, and the presence of palpable splenomegaly. CKD was univariately associated with inferior thrombosis-free survival in the entire cohort, as well as in both ET and PV patients. These results remained significant in the multivariate Cox regression models when adjusted to disease-specific risk models. Therefore, CKD could be a risk factor for thrombosis in ET and PV patients. Additional studies on a larger number of patients are needed to confirm our findings and to elucidate whether the addition of CKD to the current risk stratification models might improve prognostication in ET and PV patients.


Assuntos
Policitemia Vera/complicações , Insuficiência Renal Crônica/complicações , Trombocitemia Essencial/complicações , Trombose/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Insuficiência Renal Crônica/diagnóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Trombose/mortalidade
15.
Ann Intern Med ; 173(5): 350-361, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32422076

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality. OBJECTIVE: To evaluate the pathologic changes of organ systems and the clinicopathologic basis for severe and fatal outcomes. DESIGN: Prospective autopsy study. SETTING: Single pathology department. PARTICIPANTS: 11 deceased patients with COVID-19 (10 of whom were selected at random for autopsy). MEASUREMENTS: Systematic macroscopic, histopathologic, and viral analysis (SARS-CoV-2 on real-time polymerase chain reaction assay), with correlation of pathologic and clinical features, including comorbidities, comedication, and laboratory values. RESULTS: Patients' age ranged from 66 to 91 years (mean, 80.5 years; 8 men, 3 women). Ten of the 11 patients received prophylactic anticoagulant therapy; venous thromboembolism was not clinically suspected antemortem in any of the patients. Both lungs showed various stages of diffuse alveolar damage (DAD), including edema, hyaline membranes, and proliferation of pneumocytes and fibroblasts. Thrombosis of small and mid-sized pulmonary arteries was found in various degrees in all 11 patients and was associated with infarction in 8 patients and bronchopneumonia in 6 patients. Kupffer cell proliferation was seen in all patients, and chronic hepatic congestion in 8 patients. Other changes in the liver included hepatic steatosis, portal fibrosis, lymphocytic infiltrates and ductular proliferation, lobular cholestasis, and acute liver cell necrosis, together with central vein thrombosis. Additional frequent findings included renal proximal tubular injury, focal pancreatitis, adrenocortical hyperplasia, and lymphocyte depletion of spleen and lymph nodes. Viral RNA was detectable in pharyngeal, bronchial, and colonic mucosa but not bile. LIMITATION: The sample was small. CONCLUSION: COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency. Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation. Studies are needed to further understand the thrombotic complications of COVID-19, together with the roles for strict thrombosis prophylaxis, laboratory and imaging studies, and early anticoagulant therapy for suspected pulmonary arterial thrombosis or thromboembolism. PRIMARY FUNDING SOURCE: None.


Assuntos
Infecções por Coronavirus/mortalidade , Pneumonia Viral/mortalidade , Artéria Pulmonar , Trombose/mortalidade , Idoso , Idoso de 80 Anos ou mais , Autopsia , Betacoronavirus , Feminino , Humanos , Masculino , Pandemias , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real
16.
Thromb Haemost ; 120(5): 832-846, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32369854

RESUMO

BACKGROUND: Low molecular weight heparins (LMWH) are often used as a first-line therapy for the prevention of thrombosis in cancer patients. Preclinical evidence from animal models suggests that LMWH may have antimetastatic properties. Clinical evidence of this effect is inconclusive. The objective of this systematic review is to evaluate the effect of LMWH on overall survival in patients with solid tumor malignancies. METHODS: MEDLINE, Embase, and The Cochrane Central Register of Controlled trials were searched from inception to November 26, 2018. We included randomized controlled trials that compared LMWH to placebo, a no-treatment arm, or a short-term prophylactic course of LMWH in adult patients with solid tumors. The primary outcome was overall survival. Secondary outcomes included progression-free survival, the occurrence of venous thromboembolism, and major bleeding events. The risk of bias was assessed in duplicate using the Cochrane Risk-of-Bias tool. RESULTS: Forty-five articles were included in the review. Overall, no difference in overall survival was observed between groups (risk ratio: 1.00; 95% confidence interval: 0.98-1.02; I2 = 36.5%). In our a priori defined subgroup analyses, the effect was not shown to vary by the type of LMWH, duration of LMWH use, length of study follow-up, comparator used in the study, or the setting in which the LMWH was administered. The majority of studies had an unclear risk of bias for at least one methodological criterion. CONCLUSION: Although LMWH is thought to possess antimetastatic properties and thus have the potential to improve survival in cancer patients, existing data do not support this hypothesis.


Assuntos
Anticoagulantes/administração & dosagem , Heparina de Baixo Peso Molecular/administração & dosagem , Neoplasias/tratamento farmacológico , Trombose/prevenção & controle , Anticoagulantes/efeitos adversos , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Neoplasias/sangue , Neoplasias/diagnóstico , Neoplasias/mortalidade , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Trombose/sangue , Trombose/diagnóstico , Trombose/mortalidade , Fatores de Tempo
17.
Intensive Care Med ; 46(6): 1089-1098, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32367170

RESUMO

PURPOSE: Little evidence of increased thrombotic risk is available in COVID-19 patients. Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection. METHODS: All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included. Medical history, symptoms, biological data and imaging were prospectively collected. Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients. RESULTS: 150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points). Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting. Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO. Most patients (> 95%) had elevated D-dimer and fibrinogen. No patient developed disseminated intravascular coagulation. Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant. Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs. 2.1%, p < 0.008). Coagulation parameters significantly differed between the two groups. CONCLUSION: Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications. Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.


Assuntos
Anticoagulantes/uso terapêutico , Betacoronavirus/patogenicidade , Infecções por Coronavirus/fisiopatologia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Pneumonia Viral/fisiopatologia , Embolia Pulmonar/fisiopatologia , Síndrome Respiratória Aguda Grave/fisiopatologia , Trombose/fisiopatologia , Idoso , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Estado Terminal , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , França/epidemiologia , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Pontuação de Propensão , Estudos Prospectivos , Embolia Pulmonar/complicações , Embolia Pulmonar/mortalidade , Embolia Pulmonar/virologia , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/mortalidade , Síndrome Respiratória Aguda Grave/virologia , Trombose/etiologia , Trombose/mortalidade , Trombose/virologia
18.
Minerva Med ; 111(2): 173-180, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32338843

RESUMO

INTRODUCTION: Clinical data on short mandatory dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy, compared with prolonged DAPT in patients undergoing percutaneous coronary intervention (PCI) are insufficient. We aim to evaluate the effectiveness and safety of P2Y12 inhibitor monotherapy and prolonged DAPT after short mandatory DAPT on cardiovascular events in patients undergoing PCI. EVIDENCE ACQUISITION: A systematic literature search was performed in seven medical databases from building the database until July 2019. Three studies with randomized controlled trial (RCTs), totaling 21,970 patients, were included in this meta-analysis. The included studies were assessed by the Cochrane risk of bias and analyzed by Review Manager v. 5.3 software. EVIDENCE SYNTHESIS: Our result of pooled analysis showed that there was noninferior rates of in major adverse cardiac and cerebrovascular events (MACCE), stroke, myocardial infarction and cardiac death between short mandatory DAPT followed by P2Y12 inhibitor monotherapy and prolonged DAPT in patients undergoing PCI. Pooled analysis showed that short mandatory DAPT followed by P2Y12 inhibitor monotherapy could significantly reduce the risk of bleeding BARC type 2-5 (OR=0.47, 95% CI: 0.31-0.70, P=0.002), compared with prolonged DAPT in patients undergoing PCI. However, Pooled analysis showed that short mandatory DAPT followed by P2Y12 inhibitor monotherapy was not associated with BARC type 3-5, compared with prolonged DAPT. CONCLUSIONS: This meta-analysis demonstrated that short mandatory DAPT followed by P2Y12 inhibitor monotherapy compared with prolonged DAPT resulted in noninferior rates of MACCE, all-cause mortality, cardiac death, stroke, myocardial infarction and stent thrombosis. Furthermore, short mandatory DAPT followed by P2Y12 inhibitor monotherapy could significantly reduce the risk of bleeding BARC type 2-5.


Assuntos
Aspirina/efeitos adversos , Cardiopatias/mortalidade , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Acidente Vascular Cerebral/mortalidade , Aspirina/uso terapêutico , Causas de Morte , Cardiopatias/induzido quimicamente , Humanos , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/mortalidade , Avaliação de Resultados em Cuidados de Saúde , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Stents/efeitos adversos , Acidente Vascular Cerebral/induzido quimicamente , Trombose/induzido quimicamente , Trombose/mortalidade
19.
Transplant Proc ; 52(2): 543-545, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32085861

RESUMO

AIM: To analyze the causes of liver retransplantation (LRT), which mostly depend on recipient factors. MATERIALS AND METHODS: A descriptive, observational, and unicentric study including patients who underwent an LRT in a tertiary medical center between April 2002 and December 2018. Recipient, donor, and liver transplant data were collected. RESULTS: During the period under review a total of 468 transplants were made; among them, 32 (6.8%) were LRT. The most common indication (25%) was hepatic artery thrombosis (HAT) developing ischemic cholangiopathy followed by chronic rejection (21.8%). Late LRT was performed in 71.8%. A total of 96.8% of donations were after brain death with a donor median age of 65 years. Six patients (18.7%) had HAT as a postoperative complication. The recipients' 3-, 6-, and 12-month overall survival was 72.7%, 54.6%, and 51.5%, respectively, and the 5-year was 46.8%. Leading cause of death was septic shock (42.1%). CONCLUSION: In our patients, the most common cause of LRT is HAT. We had an LRT rate of 6.8%, which is consistent with national and international registers.


Assuntos
Artéria Hepática/cirurgia , Transplante de Fígado/mortalidade , Complicações Pós-Operatórias/cirurgia , Reoperação/mortalidade , Doadores de Tecidos/estatística & dados numéricos , Adulto , Idoso , Feminino , Sobrevivência de Enxerto , Humanos , Hepatopatias/mortalidade , Hepatopatias/cirurgia , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Reoperação/métodos , Taxa de Sobrevida , Centros de Atenção Terciária , Trombose/etiologia , Trombose/mortalidade , Trombose/cirurgia
20.
Arch Cardiovasc Dis ; 113(4): 263-275, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32057662

RESUMO

Transcatheter aortic valve replacement (TAVR) has emerged as the treatment of choice for patients with severe aortic stenosis deemed at high or intermediate risk for cardiac surgery. In light of the latest literature advances, TAVR will undoubtedly concern a growing number of patients because of the progressive extension of its indications. Whereas significant efforts have been made to reduce the burden of periprocedural complications, TAVR still exposes patients to a sizeable number of adverse outcomes, including thrombotic and bleeding events. Although contradictory, these two phenomena are closely related to pathophysiological processes inherent to flow disturbances induced by aortic stenosis itself, but also to a complex interaction between bioprosthetic valves and native tissues in frail patients clustering various co-morbidities. Reinforcing this paradigm, multiple TAVR studies have emphasized the view that both thrombosis and bleeding events have a deleterious effect on patient outcomes. Therefore, we sought to perform a comprehensive translational review of the current literature addressing the pathophysiological mechanisms leading to thrombosis and bleeding after TAVR, and underline innovative strategies aimed at reducing these complications.


Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Hemorragia Pós-Operatória/etiologia , Trombose/etiologia , Substituição da Valva Aórtica Transcateter/efeitos adversos , Animais , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Estenose da Valva Aórtica/mortalidade , Tomada de Decisão Clínica , Fibrinolíticos/administração & dosagem , Fibrinolíticos/efeitos adversos , Próteses Valvulares Cardíacas , Humanos , Hemorragia Pós-Operatória/mortalidade , Hemorragia Pós-Operatória/prevenção & controle , Medição de Risco , Fatores de Risco , Trombose/mortalidade , Trombose/prevenção & controle , Fatores de Tempo , Substituição da Valva Aórtica Transcateter/instrumentação , Substituição da Valva Aórtica Transcateter/mortalidade , Pesquisa Médica Translacional , Resultado do Tratamento
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