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1.
BMJ Case Rep ; 13(9)2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948531

RESUMO

We are reporting a middle-aged male patient with polycythaemia vera comorbidity. The patient was exhibiting symptoms including fever, cough and shortness of breath and was found to have acute pulmonary embolism. He was diagnosed with SARS-CoV-2. This case suggests that a high index of suspicion should be taken into consideration for thromboembolic events, when treating patients with COVID-19 with breathing difficulty and low oxygen saturation levels, especially in those who have underlying predisposing conditions for coagulopathy.


Assuntos
Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Policitemia Vera/complicações , Embolia Pulmonar/etiologia , Betacoronavirus , Angiografia por Tomografia Computadorizada , Infecções por Coronavirus/sangue , Diabetes Mellitus Tipo 2/complicações , Ecocardiografia , Fibrinolíticos/uso terapêutico , Heparina/uso terapêutico , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Policitemia Vera/sangue , Artéria Pulmonar/diagnóstico por imagem , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/tratamento farmacológico , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/uso terapêutico , Tomografia Computadorizada por Raios X , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/etiologia
2.
Korean J Gastroenterol ; 76(3): 164-166, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32969365

RESUMO

The World Health Organization has declared novel coronavirus disease 2019 (COVID-19) a global public health emergency. Although respiratory symptoms predominate in COVID-19, thrombosis can occur in patients with COVID-19. This paper reports a case of an 82-year-old female with a prior medical history of hypertension, diabetes presenting with fever and cough, and was diagnosed with COVID-19. The patient subsequently developed progressively worsening of abdominal distention, tenderness, and underwent emergent laparotomy. She was found to have a gangrenous colon. This case adds to the limited literature regarding the extrapulmonary complications of COVID-19.


Assuntos
Colite/diagnóstico , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Trombose Venosa/diagnóstico , Abdome/diagnóstico por imagem , Abdome/cirurgia , Doença Aguda , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Betacoronavirus/isolamento & purificação , Colite/patologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Feminino , Heparina/uso terapêutico , Humanos , Laparotomia , Necrose , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Tomografia Computadorizada por Raios X , Trombose Venosa/complicações , Trombose Venosa/tratamento farmacológico
3.
Trials ; 21(1): 769, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895056

RESUMO

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


Assuntos
Antitrombinas/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Fragmentos de Peptídeos/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Respiração Artificial , Síndrome do Desconforto Respiratório do Adulto/terapia , Anticoagulantes/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/sangue , Estado Terminal , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Hirudinas , Humanos , Pandemias , Tempo de Tromboplastina Parcial , Pneumonia Viral/sangue , Catar , Proteínas Recombinantes/uso terapêutico
4.
Int Heart J ; 61(5): 993-998, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32921671

RESUMO

Venous thromboembolism (VTE) is a life-threatening complication after trauma. Several studies have reported VTE prophylaxis using low-molecular-weight heparin; however, there is no consensus for prophylaxis after trauma. This study aimed to assess the efficacy and safety of our new anticoagulation therapy protocol using unfractionated heparin (UFH) plus intermittent pneumatic compression (IPC) to prevent post-traumatic VTE in high-risk trauma patients.This study enrolled 70 trauma patients who were admitted to the emergency medical center of Nagasaki University Hospital and had Risk Assessment Profile (RAP) scores ≥ 5. After stopping bleeding at the trauma site, all patients received intravenous UFH (10,000 U/day) plus IPC, which was continued for 14 days or until the patients could walk. On days 7 and 14, all patients underwent lower extremity sonography for deep-vein thrombosis screening. VTE incidences between patients with the above intervention and historical controls with IPC alone were compared.No significant differences in age, sex, and the RAP score were observed between the 105 controls and intervention patients. VTE occurrence was fewer in patients with the intervention (14.3%) than in the controls (28.6%; P = 0.029). No hemorrhagic complications occurred after UFH administration. Multivariable logistic analysis revealed a significant association between the intervention and low incidence of VTE (odds ratio: 0.390; 95% confidence interval: 0.163-0.913; P = 0.030).Routine UFH administration with IPC may prevent post-traumatic VTE without adverse events.


Assuntos
Anticoagulantes/uso terapêutico , Heparina/uso terapêutico , Dispositivos de Compressão Pneumática Intermitente , Embolia Pulmonar/prevenção & controle , Tromboembolia Venosa/prevenção & controle , Trombose Venosa/prevenção & controle , Ferimentos e Lesões/terapia , Idoso , Estudos de Coortes , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Hospitalização , Humanos , Escala de Gravidade do Ferimento , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tempo de Tromboplastina Parcial , Medição de Risco , Trombofilia/sangue , Ferimentos e Lesões/sangue
5.
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
6.
Adv Biol Regul ; 77: 100735, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32773098

RESUMO

The novel Corona virus infection (Covid-19) first identified in China in December 2019 has rapidly progressed in pandemic leading to significant mortality and unprecedented challenge for healthcare systems. Although the clinical spectrum of Covid-19 is variable, acute respiratory failure and systemic coagulopathy are common in severe Covid-19 patients. Lung is an important target of the SARS-CoV-2 virus causing eventually acute respiratory distress syndrome associated to a thromboinflammatory state. The cytokinic storm, thromboinflammation and pulmonary tropism are the bedrock of tissue lesions responsible for acute respiratory failure and for prolonged infection that may lead to multiple organ failure and death. The thrombogenicity of this infectious disease is illustrated by the high frequency of thromboembolic events observed even in Covid-19 patients treated with anticoagulation. Increased D-Dimers, a biomarker reflecting activation of hemostasis and fibrinolysis, and low platelet count (thrombocytopenia) are associated with higher mortality in Covid-19 patients. In this review, we will summarize our current knowledge on the thromboembolic manifestations, the disturbed hemostatic parameters, and the thromboinflammatory conditions associated to Covid-19 and we will discuss the modalities of anticoagulant treatment or other potential antithrombotic options.


Assuntos
Anticoagulantes/uso terapêutico , Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Síndrome da Liberação de Citocina/complicações , Coagulação Intravascular Disseminada/complicações , Pneumonia Viral/complicações , Embolia Pulmonar/complicações , Insuficiência Respiratória/complicações , Doença Aguda , Biomarcadores/sangue , Plaquetas/efeitos dos fármacos , Plaquetas/patologia , Plaquetas/virologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/virologia , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/tratamento farmacológico , Coagulação Intravascular Disseminada/virologia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Heparina/uso terapêutico , Interações Hospedeiro-Patógeno , Humanos , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/virologia , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/tratamento farmacológico , Insuficiência Respiratória/virologia , Análise de Sobrevida
7.
Saudi Med J ; 41(8): 779-790, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32789417

RESUMO

[No Abstract Available]    Saudi Med J 2020; Vol. 41 (8): 779-790doi: 10.15537/smj.2020.8.25222 How to cite this article:Yaser A. Faden, Nadia A. Alghilan,  Samiha H. Alawami, Eman S. Alsulmi, Hythem A. Alsum, Yasir A. Katib, Yasser S. Sabr, Fadwah H. Tahir, Nabeel S. Bondagji. Saudi Society of Maternal-Fetal Medicine guidance on pregnancy and coronavirus disease 2019. Saudi Med J 2020; Vol. 41 (8): 779-790. doi: 10.15537/smj.2020.8.25222.


Assuntos
Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Complicações Infecciosas na Gravidez/terapia , Cuidado Pré-Natal/métodos , Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus , Anormalidades Congênitas/virologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/transmissão , Estado Terminal , Parto Obstétrico/métodos , Feminino , Heparina/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Recém-Nascido , Transmissão Vertical de Doença Infecciosa , Sulfato de Magnésio/uso terapêutico , Pandemias , Perinatologia , Equipamento de Proteção Individual , Pneumonia Viral/transmissão , Cuidado Pós-Natal , Gravidez , Resultado da Gravidez , Arábia Saudita , Sociedades Médicas , Tromboembolia/prevenção & controle , Tocolíticos/uso terapêutico
8.
Zhonghua Xin Xue Guan Bing Za Zhi ; 48(8): 648-654, 2020 Aug 24.
Artigo em Chinês | MEDLINE | ID: mdl-32847320

RESUMO

Objective: To compare the safety and efficacy of bivalirudin versus unfractionated heparin during perioperative period of percutaneous coronary intervention(PCI) in real-world. Methods: A total of 13 097 serial patients who underwent PCI from January 2016 to November 2018 in the Northern Theater Command were enrolled in the present study. Patients were stratified as the bivalirudin group or the heparin group according to antithrombotic therapy during PCI. The primary efficiency endpoint was 30-day net adverse clinical event(NACE), defined as all-cause death, re-infarction, urgent target lesion revascularization (uTLR), stroke or any bleeding. The second efficiency endpoint was 30-day major cardiac and cerebral events (MACCE), defined as all-cause death, re-infarction, uTLR and stroke. Additional end points included the rates of stent thrombosis at 30 days. Propensity scores included clinical and demographic variables, with 1∶2 matching. Compared the incidence of events above between the two groups before and after matching. Results: Among the 13 097 included patients(age was (61±10) years old), 3 421 (26.1%) were female. And 2 734 patients were divided into the bivalirudin group, and 10 363 patients to the heparin group(5 468 after matching). Before propensity score matching, patients in bivalirudin group were older and received higher levels of CRUSADE score than heparin group. These patients were more likely to have hypertension and more with ST-segment elevation acute coronary syndromes(all P<0.05). After propensity score matching, the incidence of 30-day NACE(3.8%(103/2 734) vs.5.0%(271/5 468), P=0.015) and any bleeding (2.0%(54/2 734) vs. 2.8%(151/5 468), P=0.032) in the bivalirudin group were lower than that in the heparin group, but the incidence of MACCE (1.9%(51/2 734) vs. 2.3%(127/5 468), P=0.180) and stent thrombosis (0.1%(2/2 734) vs. 0.1%(3/5 468), P=1.000) were comparable between the two groups. Conclusion: The risk of bleeding and the incidence of NACE are significantly lower for patients using bivalirudin during perioperative period of PCI compared to heparin, without significant differences in ischemic events.


Assuntos
Heparina/uso terapêutico , Intervenção Coronária Percutânea , Idoso , Anticoagulantes/uso terapêutico , Feminino , Hirudinas , Humanos , Pessoa de Meia-Idade , Fragmentos de Peptídeos , Período Perioperatório , Proteínas Recombinantes , Resultado do Tratamento
9.
EBioMedicine ; 59: 102969, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32853989

RESUMO

Coronavirus disease-2019 (COVID-19) is associated with severe inflammation in mainly the lung, and kidney. Reports suggest a beneficial effect of the use of heparin/low molecular weight heparin (LMWH) on mortality in COVID-19. In part, this beneficial effect could be explained by the anticoagulant properties of heparin/LMWH. Here, we summarise potential beneficial, non-anticoagulant mechanisms underlying treatment of COVID-19 patients with heparin/LMWH, which include: (i) Inhibition of heparanase activity, responsible for endothelial leakage; (ii) Neutralisation of chemokines, and cytokines; (iii) Interference with leukocyte trafficking; (iv) Reducing viral cellular entry, and (v) Neutralisation of extracellular cytotoxic histones. Considering the multiple inflammatory and pathogenic mechanisms targeted by heparin/LMWH, it is warranted to conduct clinical studies that evaluate therapeutic doses of heparin/LMWH in COVID-19 patients. In addition, identification of specific heparin-derived sequences that are functional in targeting non-anticoagulant mechanisms may have even higher therapeutic potential for COVID-19 patients, and patients suffering from other inflammatory diseases.


Assuntos
Anti-Inflamatórios/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Heparina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Betacoronavirus/isolamento & purificação , Betacoronavirus/fisiologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Glucuronidase/antagonistas & inibidores , Glucuronidase/metabolismo , Heparina/metabolismo , Heparina/farmacologia , Heparina de Baixo Peso Molecular/metabolismo , Heparina de Baixo Peso Molecular/farmacologia , Heparina de Baixo Peso Molecular/uso terapêutico , Histonas/sangue , Histonas/metabolismo , Humanos , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Internalização do Vírus/efeitos dos fármacos
10.
Curr Probl Cardiol ; 45(9): 100648, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32703535

RESUMO

The exceptional outbreak of COVID-19 pandemic has let the scientific community to work closely and quickly learnt things in a very short period of time. This has let us recognize that thromboembolic complications are responsible for morbidity and mortality among the COVID-19 infected patients. Available data have suggested a possible multifactorial basis of these complications, and while efforts are being made to treat this infection, preventive measures with the use of systemic anticoagulation were quickly adopted to deal with this issue. Despite obvious benefits as appeared with the use of systemic anticoagulation, most of the emerged data were retrospective, hence raise questions on the possible interplay of the confounders as well as long-term benefits and safety of systemic anticoagulation.


Assuntos
Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/sangue , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Tromboembolia/sangue , Betacoronavirus , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/etiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/tratamento farmacológico , Coagulação Intravascular Disseminada/etiologia , Células Endoteliais , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Tromboembolia/tratamento farmacológico , Tromboembolia/etiologia , Receptores Toll-Like/metabolismo , Fator de von Willebrand/metabolismo
14.
Clin Rheumatol ; 39(9): 2529-2543, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32654082

RESUMO

The pathogenesis of Coronavirus disease 2019 (COVID-19) is gradually being comprehended. A high number of thrombotic episodes are reported, along with the mortality benefits of heparin. COVID-19 can be viewed as a prothrombotic disease. We overviewed the available evidence to explore this possibility. We identified various histopathology reports and clinical case series reporting thromboses in COVID-19. Also, multiple coagulation markers support this. COVID-19 can be regarded as a risk factor for thrombosis. Applying the principles of Virchow's triad, we described abnormalities in the vascular endothelium, altered blood flow, and platelet function abnormalities that lead to venous and arterial thromboses in COVID-19. Endothelial dysfunction, activation of the renin-angiotensin-aldosterone system (RAAS) with the release of procoagulant plasminogen activator inhibitor (PAI-1), and hyperimmune response with activated platelets seem to be significant contributors to thrombogenesis in COVID-19. Stratifying risk of COVID-19 thromboses should be based on age, presence of comorbidities, D-dimer, CT scoring, and various blood cell ratios. Isolated heparin therapy may not be sufficient to combat thrombosis in this disease. There is an urgent need to explore newer avenues like activated protein C, PAI-1 antagonists, and tissue plasminogen activators (tPA). These should be augmented with therapies targeting RAAS, antiplatelet drugs, repurposed antiinflammatory, and antirheumatic drugs. Key Points • Venous and arterial thromboses in COVID-19 can be viewed through the prism of Virchow's triad. • Endothelial dysfunction, platelet activation, hyperviscosity, and blood flow abnormalities due to hypoxia, immune reactions, and hypercoagulability lead to thrombogenesis in COVID-19. • There is an urgent need to stratify COVID-19 patients at risk for thrombosis using age, comorbidities, D-dimer, and CT scoring. • Patients with COVID-19 at high risk for thrombosis should be put on high dose heparin therapy.


Assuntos
Infecções por Coronavirus/sangue , Endotélio Vascular/metabolismo , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/sangue , Trombofilia/sangue , Trombose/sangue , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anticoagulantes/uso terapêutico , Betacoronavirus/metabolismo , Plaquetas , Viscosidade Sanguínea , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/metabolismo , Endotélio Vascular/fisiopatologia , Produtos de Degradação da Fibrina e do Fibrinogênio , Fibrinogênio/metabolismo , Fibrinolíticos/uso terapêutico , Heparina/uso terapêutico , Humanos , Pandemias , Inibidor 1 de Ativador de Plasminogênio/sangue , Ativação Plaquetária , Inibidores da Agregação de Plaquetas/uso terapêutico , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/metabolismo , Índice de Gravidade de Doença , Trombofilia/etiologia , Trombofilia/metabolismo , Trombose/tratamento farmacológico , Trombose/etiologia , Ativador de Plasminogênio Tecidual/sangue , Ativador de Plasminogênio Tecidual/uso terapêutico
15.
BMC Infect Dis ; 20(1): 476, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631238

RESUMO

BACKGROUND: Blood culture-negative endocarditis (BCNE) is diagnosed in 2-7% of patients with infective endocarditis (IE) and recent antibiotic use is a known risk factor. Altered mental status may be a presenting symptom. Besides empiric antibiotics, intravenous anticoagulation using heparin may have a role in the management of such patients. CASE PRESENTATION: A 23-year-old male patient was referred to our center with fever, altered mental status and abnormal gait. Neurologic examination revealed Wernicke's aphasia. Cardiac auscultation revealed systolic murmur at the left sternal border. ECG (electrocardiogram) was unremarkable. Brain MRI showed multiple cerebellar lesions. Transthoracic echocardiography (TTE) demonstrated three large masses on the right ventricle (RV), tricuspid valve (TV), and anterior mitral valve (MV) leaflet. Blood cultures (three sets) were negative. Intravenous heparin therapy was administered. After 48 h, the second TTE demonstrated that one valvular lesion disappeared and the other two lesions showed a significant decrease in size. The patient's neurological symptoms resolved gradually. Further workup for collagen vascular disorders did not show any abnormality. CONCLUSION: BCNE should be considered in patients with fever and neurologic manifestations. TTE should be performed to detect valvular abnormalities. Intravenous heparin could be used in such patients when TTE demonstrate valvular vegetations.


Assuntos
Anticoagulantes/uso terapêutico , Afasia de Wernicke/tratamento farmacológico , Hemocultura , Ecocardiografia , Endocardite Bacteriana/diagnóstico por imagem , Heparina/uso terapêutico , Administração Intravenosa , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Anticoagulantes/administração & dosagem , Afasia de Wernicke/microbiologia , Endocardite Bacteriana/sangue , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Heparina/administração & dosagem , Humanos , Masculino , Valva Mitral/diagnóstico por imagem , Valva Mitral/patologia , Resultado do Tratamento , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/patologia , Adulto Jovem
16.
Bone Joint J ; 102-B(7_Supple_B): 71-77, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32600195

RESUMO

AIMS: We studied the safety and efficacy of multimodal thromboprophylaxis in patients with a history of venous thromboembolism (VTE) who undergo total hip arthroplasty (THA) within the first 120 postoperative days, and the mortality during the first year. Multimodal prophylaxis includes discontinuation of procoagulant medications, VTE risk stratification, regional anaesthesia, an intravenous bolus of unfractionated heparin prior to femoral preparation, rapid mobilization, the use of pneumatic compression devices, and chemoprophylaxis tailored to the patient's risk of VTE. METHODS: Between 2004 to 2018, 257 patients with a proven history of VTE underwent 277 primary elective THA procedures by two surgeons at a single institution. The patients had a history of deep vein thrombosis (DVT) (186, 67%), pulmonary embolism (PE) (43, 15.5%), or both (48, 17.5%). Chemoprophylaxis included aspirin (38 patients), anticoagulation (215 patients), or a combination of aspirin and anticoagulation (24 patients). A total of 50 patients (18%) had a vena cava filter in situ at the time of surgery. Patients were followed for 120 days to record complications, and for one year to record mortality. RESULTS: Postoperative VTE was diagnosed in seven patients (2.5%): DVT in five, and PE with and without DVT in one patient each. After hospitalization, three patients required readmiss-ion for evacuation of a haematoma, one for wound drainage, and one for monitoring of an elevated international normalized ratio (INR). Seven patients died (2.5%). One patient died five months postoperatively of a PE during open thrombectomy. She had discontinued anticoagulation. One patient died of a haemorrhagic stroke while receiving Coumadin. PE or bleeding was not suspected in the remaining five fatalities. CONCLUSION: Multimodal prophylaxis is safe and effective in patients with a history of VTE. Postoperative anticoagulation should be prudent as very few patients developed VTE (2.5%) or died of suspected or confirmed PE. Mortality during the first year was mostly unrelated to either VTE or bleeding. Cite this article: Bone Joint J 2020;102-B(7 Supple B):71-77.


Assuntos
Artroplastia de Quadril , Tromboembolia Venosa/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestesia por Condução , Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Quimioprevenção , Deambulação Precoce , Procedimentos Cirúrgicos Eletivos , Feminino , Seguimentos , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Dispositivos de Compressão Pneumática Intermitente , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Complicações Pós-Operatórias , Estudos Retrospectivos , Fatores de Risco , Rivaroxabana/uso terapêutico , Varfarina/uso terapêutico
17.
Swiss Med Wkly ; 150: w20301, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32640479

RESUMO

AIMS OF THE STUDY: Many centres have noticed a high number of venous thromboembolism (VTE) events among critically ill inpatients with COVID-19 pneumonia. The aims of this study were (1) to summarise the reported risk of VTE associated with COVID-19 infections and (2) to summarise guidance documents on thromboprophylaxis in COVID-19 patients, in a systematic review. METHODS: We systematically searched for peer-reviewed evidence on the risk of VTE in patients with COVID-19, in PubMed, Embase and Twitter, and for guidelines or guidance documents for thromboprophylaxis, from international or national societies relevant to the field of thrombosis and haemostasis, up to April 30 2020. RESULTS: We found 11 studies (1 clinical trial, 7 retrospective cohorts and 3 prospective cohorts), which included a range of 16 to 388 in patients with COVID-19 (total of 1369 inpatients). The diagnoses of COVID-19 and VTE were of high quality, but the follow-up was often unclear. Most studies reported universal in-hospital thromboprophylaxis. Among all inpatients and among intensive care unit (ICU) inpatients with COVID-19, reported risks of VTE were 4.4–8.2% (three studies) and 0–35.3% (six studies), respectively. Two studies at least partially screened for VTE in ICU inpatients with COVID-19, and found risks of 24.7–53.8%. We found 12 guidelines for thromboprophylaxis of COVID-19 patients. The majority suggested universal pharmacological thromboprophylaxis in all COVID-19 inpatients, but there was heterogeneity in the suggested intensity of thromboprophylaxis: seven advised considering intensified doses of heparin according to the clinical or biological severity of the disease, especially in the ICU setting. CONCLUSIONS: Venous thromboembolism very commonly complicates the clinical course of inpatients with COVID-19, despite thromboprophylaxis. The risk appears highest among critically ill inpatients. We found no estimates of risks among outpatients. Many questions remain unresolved, as delineated by the heterogeneity of national and international guidelines. This situation calls for fast randomised clinical trials, comparing different schemes of thromboprophylaxis in COVID-19 inpatients.


Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Embolia Pulmonar/epidemiologia , Tromboembolia Venosa/epidemiologia , Trombose Venosa/epidemiologia , Anticoagulantes/uso terapêutico , Betacoronavirus , Fondaparinux/uso terapêutico , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Pandemias , Guias de Prática Clínica como Assunto , Embolia Pulmonar/prevenção & controle , Risco , Tromboembolia Venosa/prevenção & controle , Trombose Venosa/prevenção & controle
18.
Anal Chem ; 92(16): 10930-10934, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32678978

RESUMO

The emergence and rapid proliferation of the novel coronavirus (SARS-CoV-2) resulted in a global pandemic, with over 6,000,000 cases and nearly 400,000 deaths reported worldwide by the end of May 2020. A rush to find a cure prompted re-evaluation of a range of existing therapeutics vis-à-vis their potential role in treating COVID-19, placing a premium on analytical tools capable of supporting such efforts. Native mass spectrometry (MS) has long been a tool of choice in supporting the mechanistic studies of drug/therapeutic target interactions, but its applications remain limited in the cases that involve systems with a high level of structural heterogeneity. Both SARS-CoV-2 spike protein (S-protein), a critical element of the viral entry to the host cell, and ACE2, its docking site on the host cell surface, are extensively glycosylated, making them challenging targets for native MS. However, supplementing native MS with a gas-phase ion manipulation technique (limited charge reduction) allows meaningful information to be obtained on the noncovalent complexes formed by ACE2 and the receptor-binding domain (RBD) of the S-protein. Using this technique in combination with molecular modeling also allows the role of heparin in destabilizing the ACE2/RBD association to be studied, providing critical information for understanding the molecular mechanism of its interference with the virus docking to the host cell receptor. Both short (pentasaccharide) and relatively long (eicosasaccharide) heparin oligomers form 1:1 complexes with RBD, indicating the presence of a single binding site. This association alters the protein conformation (to maximize the contiguous patch of the positive charge on the RBD surface), resulting in a notable decrease in its ability to associate with ACE2. The destabilizing effect of heparin is more pronounced in the case of the longer chains due to the electrostatic repulsion between the low-pI ACE2 and the heparin segments not accommodated on the RBD surface. In addition to providing important mechanistic information on attenuation of the ACE2/RBD association by heparin, the study demonstrates the yet untapped potential of native MS coupled to gas-phase ion chemistry as a means of facilitating rational repurposing of the existing medicines for treating COVID-19.


Assuntos
Infecções por Coronavirus/patologia , Heparina/metabolismo , Espectrometria de Massas/métodos , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/patologia , Betacoronavirus/isolamento & purificação , Betacoronavirus/metabolismo , Sítios de Ligação , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Gases/química , Heparina/farmacologia , Heparina/uso terapêutico , Humanos , Simulação de Dinâmica Molecular , Pandemias , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/genética , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Ligação Proteica , Domínios Proteicos , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do Vírus/efeitos dos fármacos
19.
Cochrane Database Syst Rev ; 7: CD010525, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32692430

RESUMO

BACKGROUND: People undergoing major amputation of the lower limb are at increased risk of venous thromboembolism (VTE). Risk factors for VTE in amputees include advanced age, sedentary lifestyle, longstanding arterial disease and an identifiable hypercoagulable condition. Evidence suggests that pharmacological prophylaxis (e.g. heparin, factor Xa inhibitors, vitamin K antagonists, direct thrombin inhibitors, antiplatelets) is effective in preventing deep vein thrombosis (DVT), but is associated with an increased risk of bleeding. Mechanical prophylaxis (e.g. antiembolism stockings, intermittent pneumatic compression and foot impulse devices), on the other hand, is non-invasive and has minimal side effects. However, mechanical prophylaxis is not always appropriate for people with contraindications such as peripheral arterial disease (PAD), arteriosclerosis or bilateral lower limb amputations. It is important to determine the most effective thromboprophylaxis for people undergoing major amputation and whether this is one treatment alone or in combination with another. This is an update of the review first published in 2013. OBJECTIVES: To determine the effectiveness of thromboprophylaxis in preventing VTE in people undergoing major amputation of the lower extremity. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase and Cumulative Index to Nursing and Allied Health Literature databases, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 5 November 2019. We planned to undertake reference checking of identified trials to identify additional studies. We did not apply any language restrictions. SELECTION CRITERIA: We included randomised controlled trials and quasi-randomised controlled trials which allocated people undergoing a major unilateral or bilateral amputation (e.g. hip disarticulation, transfemoral, knee disarticulation and transtibial) of the lower extremity to different types or regimens of thromboprophylaxis (including pharmacological or mechanical prophylaxis) or placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted data and assessed risk of bias. We resolved any disagreements by discussion. Outcomes of interest were VTE (DVT and pulmonary embolism (PE)), mortality, adverse events and bleeding. We used GRADE criteria to assess the certainty of the evidence. The two included studies compared different treatments, so we could not pool the data in a meta-analysis. MAIN RESULTS: We did not identify any eligible new studies for this update. Two studies with a combined total of 288 participants met the inclusion criteria for this review. Unfractionated heparin compared to low molecular weight heparin One study compared unfractionated heparin with low molecular weight heparin and found no evidence of a difference between the treatments in the prevention of DVT (odds ratio (OR) 1.23, 95% confidence interval (CI) 0.28 to 5.35; 75 participants; very low-certainty evidence). No bleeding events occurred in either group. Deaths and adverse events were not reported. This study was open-label and therefore at a high risk of performance bias. Additionally, the study did not report the method of randomisation, so the risk of selection bias was unclear. Heparin compared to placebo In the second study, there was no evidence of a benefit from heparin use in preventing PE when compared to placebo (OR 0.84, 95% CI 0.35 to 2.01; 134 participants; low-certainty evidence). Similarly, no evidence of improvement was detected when the level of amputation was considered, with a similar incidence of PE between the two treatment groups: above knee amputation (OR 0.79, 95% CI 0.31 to 1.97; 94 participants; low-certainty evidence); and below knee amputation (OR 1.53, 95% CI 0.09 to 26.43; 40 participants; low-certainty evidence). Ten participants died during the study; five underwent a post-mortem and three were found to have had a recent PE, all of whom had been on placebo (low-certainty evidence). Bleeding events were reported in less than 10% of participants in both treatment groups, but the study did not present specific data (low-certainty evidence). There were no reports of other adverse events. This study did not report the methods used to conceal allocation of treatment, so it was unclear whether selection bias occurred. However, this study appeared to be free from all other sources of bias. No study looked at mechanical prophylaxis. AUTHORS' CONCLUSIONS: We did not identify any eligible new studies for this update. As we only included two studies in this review, each comparing different interventions, there is insufficient evidence to make any conclusions regarding the most effective thromboprophylaxis regimen in people undergoing lower limb amputation. Further large-scale studies of good quality are required.


Assuntos
Amputação/efeitos adversos , Anticoagulantes/uso terapêutico , Heparina/uso terapêutico , Extremidade Inferior/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Embolia Pulmonar/prevenção & controle , Tromboembolia Venosa/prevenção & controle , Amputação/métodos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Tromboembolia Venosa/etiologia
20.
J Mol Cell Cardiol ; 146: 32-40, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32681845

RESUMO

SARS-CoV-2 causes a phenotype of pneumonia with diverse manifestation, which is termed as coronavirus disease 2019 (COVID-19). An impressive high transmission rate allows COVID-19 conferring enormous challenge for clinicians worldwide, and developing to a pandemic level. Combined with a series of complications, a part of COVID-19 patients progress into severe cases, which critically contributes to the risk of fatality. To date, coagulopathy has been found as a prominent feature of COVID-19 and severe coagulation dysfunction may be associated with poor prognosis. Coagulopathy in COVID-19 may predispose patients to hypercoagulability-related disorders including thrombosis and even fatal vascular events. Inflammatory storm, uncontrolled inflammation-mediated endothelial injury and renin angiotensin system (RAS) dysregulation are the potential mechanisms. Ongoing efforts made to develop promising therapies provide several potential strategies for hypercoagulability in COVID-19. In this review, we introduce the clinical features of coagulation and the increased vascular thrombotic risk conferred by coagulopathy according to present reports about COVID-19. The potential underlying mechanisms and emerging therapeutic avenues are discussed, emphasizing an urgent need for effective interventions.


Assuntos
Anticoagulantes/uso terapêutico , Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Síndrome da Liberação de Citocina/complicações , Coagulação Intravascular Disseminada/complicações , Pneumonia Viral/complicações , Embolia Pulmonar/complicações , Insuficiência Respiratória/complicações , Doença Aguda , Betacoronavirus/imunologia , Biomarcadores/sangue , Plaquetas/efeitos dos fármacos , Plaquetas/patologia , Plaquetas/virologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/mortalidade , Síndrome da Liberação de Citocina/virologia , Coagulação Intravascular Disseminada/tratamento farmacológico , Coagulação Intravascular Disseminada/mortalidade , Coagulação Intravascular Disseminada/virologia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Heparina/uso terapêutico , Interações Hospedeiro-Patógeno/imunologia , Humanos , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Pandemias , Tempo de Tromboplastina Parcial , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/mortalidade , Embolia Pulmonar/virologia , Insuficiência Respiratória/tratamento farmacológico , Insuficiência Respiratória/mortalidade , Insuficiência Respiratória/virologia , Análise de Sobrevida
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