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1.
Clin Appl Thromb Hemost ; 27: 1076029620987629, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33443456

RESUMO

Coagulation activation has been reported in several cohorts of patients Coronavirus Disease 2019 (COVID-19). However, the true burden of systemic coagulopathy in COVID-19 remains unknown. In this systematic review and meta-analysis, we performed a literature search using PubMed, EMBASE, and Cochrane Database to identify studies that reported the prevalence of systemic coagulopathy using established criteria in patients with COVID-19. The primary outcome was the prevalence of systemic coagulopathy (disseminated intravascular coagulation [DIC] and/or sepsis-induced coagulopathy [SIC]). Pooled prevalences and 95% confidence intervals [CIs] were calculated using random-effects model. A total of 5 studies including 1210 patients with confirmed COVID-19 were included. The pooled prevalence of systemic coagulopathy was 7.1% (95%CI: 3.2%,15.3%, I2 = 93%). The pooled prevalence of DIC (N = 721) and SIC (N = 639) were 4.3% (95%CI 1.7%, 10.4%, I2 = 84%) and 16.2% (95%CI: 9.3%, 26.8%, I2 = 74%), respectively. Only 2 studies reported the prevalence of elevated D-dimer levels with the pooled prevalence of 84.6% (95%CI: 52.0%,96.5%, I2 = 94%). Average D-dimer and fibrinogen levels were remarkably increased, while platelet counts, PT, and aPTT ratios were minimally affected in COVID-19. The estimated prevalence of systemic coagulopathy in patients with COVID-19 was low despite D-dimer elevation in most patients. Relatively low systemic coagulopathy in COVID-19 may contribute to the high incidence of thrombosis rather than bleeding in patients with COVID-19.


Assuntos
Coagulação Intravascular Disseminada , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Sepse , Trombose , /sangue , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/epidemiologia , Feminino , Humanos , Masculino , Contagem de Plaquetas , Prevalência , Sepse/sangue , Sepse/epidemiologia , Trombose/sangue , Trombose/epidemiologia
2.
Cell Death Dis ; 12(1): 50, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33414384

RESUMO

Novel coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state, characterized by abnormal coagulation parameters and by increased incidence of cardiovascular complications. With this study, we aimed to investigate the activation state and the expression of transmembrane proteins in platelets of hospitalized COVID-19 patients. We investigated transmembrane proteins expression with a customized mass cytometry panel of 21 antibodies. Platelets of 8 hospitalized COVID-19 patients not requiring intensive care support and without pre-existing conditions were compared to platelets of healthy controls (11 donors) with and without in vitro stimulation with thrombin receptor-activating peptide (TRAP). Mass cytometry of non-stimulated platelets detected an increased surface expression of activation markers P-Selectin (0.67 vs. 1.87 median signal intensity for controls vs. patients, p = 0.0015) and LAMP-3 (CD63, 0.37 vs. 0.81, p = 0.0004), the GPIIb/IIIa complex (4.58 vs. 5.03, p < 0.0001) and other adhesion molecules involved in platelet activation and platelet-leukocyte interactions. Upon TRAP stimulation, mass cytometry detected a higher expression of P-selectin in COVID-19 samples compared to controls (p < 0.0001). However, we observed a significantly reduced capacity of COVID-19 platelets to increase the expression of activation markers LAMP-3 and P-Selectin upon stimulation with TRAP. We detected a hyperactivated phenotype in platelets during SARS-CoV-2 infection, consisting of highly expressed platelet activation markers, which might contribute to the hypercoagulopathy observed in COVID-19. In addition, several transmembrane proteins were more highly expressed compared to healthy controls. These findings support research projects investigating antithrombotic and antiplatelet treatment regimes in COVID-19 patients, and provide new insights on the phenotypical platelet expression during SARS-CoV-2 infection.


Assuntos
Plaquetas/patologia , Leucócitos/patologia , Trombose/epidemiologia , Adulto , Plaquetas/metabolismo , Plaquetas/virologia , /virologia , Estudos de Casos e Controles , Feminino , Alemanha/epidemiologia , Humanos , Leucócitos/metabolismo , Leucócitos/virologia , Masculino , Pessoa de Meia-Idade , Selectina-P/metabolismo , Fragmentos de Peptídeos/metabolismo , Fenótipo , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Trombose/virologia
3.
Viruses ; 13(2)2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33499228

RESUMO

Since the emergence of COVID-19, many publications have reported associations with ABO blood types. Despite between-study discrepancies, an overall consensus has emerged whereby blood group O appears associated with a lower risk of COVID-19, while non-O blood types appear detrimental. Two major hypotheses may explain these findings: First, natural anti-A and anti-B antibodies could be partially protective against SARS-CoV-2 virions carrying blood group antigens originating from non-O individuals. Second, O individuals are less prone to thrombosis and vascular dysfunction than non-O individuals and therefore could be at a lesser risk in case of severe lung dysfunction. Here, we review the literature on the topic in light of these hypotheses. We find that between-study variation may be explained by differences in study settings and that both mechanisms are likely at play. Moreover, as frequencies of ABO phenotypes are highly variable between populations or geographical areas, the ABO coefficient of variation, rather than the frequency of each individual phenotype is expected to determine impact of the ABO system on virus transmission. Accordingly, the ABO coefficient of variation correlates with COVID-19 prevalence. Overall, despite modest apparent risk differences between ABO subtypes, the ABO blood group system might play a major role in the COVID-19 pandemic when considered at the population level.


Assuntos
Sistema ABO de Grupos Sanguíneos/sangue , Suscetibilidade a Doenças/sangue , /epidemiologia , Suscetibilidade a Doenças/epidemiologia , Suscetibilidade a Doenças/microbiologia , Suscetibilidade a Doenças/patologia , Humanos , Incidência , Isoanticorpos/sangue , Microbiota , Razão de Chances , Trombose/sangue , Trombose/epidemiologia , Trombose/microbiologia
5.
Angiology ; 72(1): 50-61, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32806925

RESUMO

To evaluate clinical implication of prediabetes, we compared a 2-year major clinical outcome including patient-oriented composite outcomes (POCOs), stent thrombosis (ST), and stroke between prediabetes and diabetes in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD). A total of 4097 patients with STEMI and MVD (normoglycemia [group A: 1001], prediabetes [group B: 1518], and diabetes [group C: 1578]) who received drug-eluting stents were evaluated. Patient-oriented composite outcomes were defined as all-cause death, recurrent myocardial infarction (MI), or any repeat revascularization. The cumulative incidences of POCOs, ST, and stroke were similar between groups B and C. The cumulative incidences of all-cause death (adjusted hazard ratio [aHR]: 1.483; 95% CI: 1.027-2.143; P = .036) and all-cause death or MI (aHR: 1.429, 95% CI: 1.034-1.974; P = .031) were higher in group B than in group A. The cumulative incidences of all-cause death (aHR: 1.563; 95% CI: 1.089-2.243; P = .015), cardiac death (aHR: 1.661; 95% CI: 1.123-2.457; P = .011), and all-cause death or MI were higher in group C than in group A. In conclusion, prediabetes could potentially have a similar impact as diabetes on major clinical outcomes in patients with STEMI and MVD.


Assuntos
Diabetes Mellitus/epidemiologia , Stents Farmacológicos , Intervenção Coronária Percutânea , Estado Pré-Diabético/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Fatores Etários , Idoso , Reanimação Cardiopulmonar , Estudos de Coortes , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Choque Cardiogênico/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Trombose/epidemiologia
7.
N Z Med J ; 133(1526): 45-54, 2020 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-33332339

RESUMO

AIMS: The incidence of left ventricular (LV) thrombus following ST segment elevation myocardial infarction (STEMI) has reduced with modern reperfusion therapies. There is scant local data on the incidence and outcomes of LV thrombus in the contemporary era of rapid reperfusion. METHODS: Patients with STEMI admitted to Auckland City Hospital between January 2014 and December 2015 were identified using the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry and their clinical notes were retrospectively reviewed. RESULTS: Among the 997 patients admitted with STEMI, 53 patients (5%) had LV thrombus. Most patients with LV thrombus had an anterior STEMI (87%). The median time from admission to echocardiography was 48 hours (range 6-552 hours); the median LV ejection fraction was 38% (range 15-53%). Oral anticoagulation was initiated in 44 (83%) patients. LV thrombus resolved in 81% by six months in 42 patients given warfarin. Total mortality at 12 months was 13%. Bleeding occurred in 11% and was the most common treatment-related morbidity. CONCLUSIONS: The incidence of LV thrombus following STEMI was low and it was associated with a low rate of stroke and systemic embolism but high mortality. Randomised studies are needed to evaluate the efficacy of NOAC's in this context.


Assuntos
Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Trombose/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ecocardiografia , Feminino , Seguimentos , Ventrículos do Coração , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Estudos Retrospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Trombose/diagnóstico , Trombose/epidemiologia
8.
Blood Adv ; 4(24): 6259-6273, 2020 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-33351119

RESUMO

Thrombosis has emerged as an important complication of coronavirus disease 2019 (COVID-19), particularly among individuals with severe illness. However, the precise incidence of thrombotic events remains uncertain due to differences in study design, patient populations, outcome ascertainment, event definitions, and reporting. In an effort to overcome some of these challenges and promote standardized data collection and reporting in clinical studies, the American Society of Hematology Research Collaborative COVID-19 Non-Malignant Hematology Task Force, in collaboration with the International Society on Thrombosis and Haemostasis COVID-19 Task Force, developed sets of data elements in the following domains: venous thromboembolism, myocardial infarction, stroke/transient ischemic attack, peripheral arterial thrombosis, bleeding, laboratory investigations, and antithrombotic therapy. Data elements in each of these domains were developed with 3 levels of detail to facilitate their incorporation into studies evaluating a range of interventions and outcomes. Previously published data elements were included where possible. The use of standardized variables in a range of clinical studies can enhance the quality of data collection, create efficiency, enhance comparison of results across studies, and facilitate future pooling of data sets.


Assuntos
/epidemiologia , Bases de Dados Factuais , Trombose/epidemiologia , Interface Usuário-Computador , Navegador , Anticoagulantes/uso terapêutico , /virologia , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , Avaliação de Resultados em Cuidados de Saúde , Vigilância em Saúde Pública , Trombose/diagnóstico , Trombose/etiologia , Trombose/terapia
9.
Artigo em Inglês | MEDLINE | ID: mdl-33038834

RESUMO

COVID-19 symptoms vary from silence to rapid death, the latter mediated by both a cytokine storm and a thrombotic storm. SARS-CoV (2003) induces Cox-2, catalyzing the synthesis, from highly unsaturated fatty acids (HUFA), of eicosanoids and docosanoids that mediate both inflammation and thrombosis. HUFA balance between arachidonic acid (AA) and other HUFA is a likely determinant of net signaling to induce a healthy or runaway physiological response. AA levels are determined by a non-protein coding regulatory polymorphisms that mostly affect the expression of FADS1, located in the FADS gene cluster on chromosome 11. Major and minor haplotypes in Europeans, and a specific functional insertion-deletion (Indel), rs66698963, consistently show major differences in circulating AA (>50%) and in the balance between AA and other HUFA (47-84%) in free living humans; the indel is evolutionarily selective, probably based on diet. The pattern of fatty acid responses is fully consistent with specific genetic modulation of desaturation at the FADS1-mediated 20:3→20:4 step. Well established principles of net tissue HUFA levels indicate that the high linoleic acid and low alpha-linoleic acid in populations drive the net balance of HUFA for any individual. We predict that fast desaturators (insertion allele at rs66698963; major haplotype in Europeans) are predisposed to higher risk and pathological responses to SARS-CoV-2 could be reduced with high dose omega-3 HUFA.


Assuntos
Infecções por Coronavirus/complicações , Ácidos Graxos Insaturados/biossíntese , Inflamação/etiologia , Metabolismo dos Lipídeos/genética , Pneumonia Viral/complicações , Trombose/etiologia , Betacoronavirus/fisiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/metabolismo , Ácidos Graxos Insaturados/genética , Predisposição Genética para Doença , Haplótipos , Humanos , Individualidade , Inflamação/epidemiologia , Inflamação/genética , Inflamação/metabolismo , Lipogênese/genética , Redes e Vias Metabólicas/genética , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/genética , Pneumonia Viral/metabolismo , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Trombose/epidemiologia , Trombose/genética , Trombose/metabolismo
10.
Ann Biol Clin (Paris) ; 78(5): 471-481, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33026344

RESUMO

COVID-19 is associated with disturbances of hemostasis in the laboratory and an increased thrombotic risk. Routine laboratory tests - activated partial thromboplastin time (aPTT), prothrombin time, Clauss fibrinogen and D-dimers levels measurement - are used for the evaluation of the thrombotic risk and the monitoring of hemostasis, but are subject to several drawbacks that may affect the reliability and clinical relevance of the delivered results. Another challenge for the hemostasis laboratory is the monitoring of heparin treatment. For instance, the issue of the monitoring of unfractionated heparin remains debated, the more so when there is a tremendous inflammatory response. This brief review considers the role of laboratory tests of hemostasis in the management of COVID-19 and discusses their main limitations to be kept in mind.


Assuntos
Infecções por Coronavirus/sangue , Infecções por Coronavirus/terapia , Hemostasia/fisiologia , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Trombose/diagnóstico , Trombose/etiologia , Trombose/prevenção & controle , Anticoagulantes/uso terapêutico , Betacoronavirus/fisiologia , Testes de Coagulação Sanguínea , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Monitoramento de Medicamentos/métodos , Hemostasia/efeitos dos fármacos , Humanos , Laboratórios Hospitalares , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Fatores de Risco , Trombose/epidemiologia
11.
N Engl J Med ; 383(15): 1447-1457, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-32865376

RESUMO

BACKGROUND: The effect of single as compared with dual antiplatelet treatment on bleeding and thromboembolic events after transcatheter aortic-valve implantation (TAVI) in patients who do not have an indication for long-term anticoagulation has not been well studied. METHODS: In a randomized, controlled trial, we assigned a subgroup of patients who were undergoing TAVI and did not have an indication for long-term anticoagulation, in a 1:1 ratio, to receive aspirin alone or aspirin plus clopidogrel for 3 months. The two primary outcomes were all bleeding (including minor, major, and life-threatening or disabling bleeding) and non-procedure-related bleeding over a period of 12 months. Most bleeding at the TAVI puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2) at 1 year, with both outcomes tested sequentially for noninferiority (noninferiority margin, 7.5 percentage points) and superiority. RESULTS: A total of 331 patients were assigned to receive aspirin alone and 334 were assigned to receive aspirin plus clopidogrel. A bleeding event occurred in 50 patients (15.1%) receiving aspirin alone and in 89 (26.6%) receiving aspirin plus clopidogrel (risk ratio, 0.57; 95% confidence interval [CI], 0.42 to 0.77; P = 0.001). Non-procedure-related bleeding occurred in 50 patients (15.1%) and 83 patients (24.9%), respectively (risk ratio, 0.61; 95% CI, 0.44 to 0.83; P = 0.005). A secondary composite 1 event occurred in 76 patients (23.0%) receiving aspirin alone and in 104 (31.1%) receiving aspirin plus clopidogrel (difference, -8.2 percentage points; 95% CI for noninferiority, -14.9 to -1.5; P<0.001; risk ratio, 0.74; 95% CI for superiority, 0.57 to 0.95; P = 0.04). A secondary composite 2 event occurred in 32 patients (9.7%) and 33 patients (9.9%), respectively (difference, -0.2 percentage points; 95% CI for noninferiority, -4.7 to 4.3; P = 0.004; risk ratio, 0.98; 95% CI for superiority, 0.62 to 1.55; P = 0.93). A total of 44 patients (13.3%) and 32 (9.6%), respectively, received oral anticoagulation during the trial. CONCLUSIONS: Among patients undergoing TAVI who did not have an indication for oral anticoagulation, the incidence of bleeding and the composite of bleeding or thromboembolic events at 1 year were significantly less frequent with aspirin than with aspirin plus clopidogrel administered for 3 months. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, 2013-003125-28; ClinicalTrials.gov number, NCT02247128.).


Assuntos
Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Hemorragia/induzido quimicamente , Inibidores da Agregação de Plaquetas/uso terapêutico , Trombose/prevenção & controle , Substituição da Valva Aórtica Transcateter , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Clopidogrel/efeitos adversos , Quimioterapia Combinada , Feminino , Hemorragia/epidemiologia , Humanos , Incidência , Masculino , Inibidores da Agregação de Plaquetas/efeitos adversos , Período Pós-Operatório , Trombose/epidemiologia
12.
Stroke ; 51(10): 3156-3168, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32897811

RESUMO

Understanding the relationship between infection and stroke has taken on new urgency in the era of the coronavirus disease 2019 (COVID-19) pandemic. This association is not a new concept, as several infections have long been recognized to contribute to stroke risk. The association of infection and stroke is also bidirectional. Although infection can lead to stroke, stroke also induces immune suppression which increases risk of infection. Apart from their short-term effects, emerging evidence suggests that poststroke immune changes may also adversely affect long-term cognitive outcomes in patients with stroke, increasing the risk of poststroke neurodegeneration and dementia. Infections at the time of stroke may also increase immune dysregulation after the stroke, further exacerbating the risk of cognitive decline. This review will cover the role of acute infections, including respiratory infections such as COVID-19, as a trigger for stroke; the role of infectious burden, or the cumulative number of infections throughout life, as a contributor to long-term risk of atherosclerotic disease and stroke; immune dysregulation after stroke and its effect on the risk of stroke-associated infection; and the impact of infection at the time of a stroke on the immune reaction to brain injury and subsequent long-term cognitive and functional outcomes. Finally, we will present a model to conceptualize the many relationships among chronic and acute infections and their short- and long-term neurological consequences. This model will suggest several directions for future research.


Assuntos
Aterosclerose/epidemiologia , Infecções/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/fisiopatologia , Aterosclerose/imunologia , Aterosclerose/fisiopatologia , Bacteriemia/epidemiologia , Bacteriemia/imunologia , Bacteriemia/fisiopatologia , Betacoronavirus , Doença Crônica , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/fisiopatologia , Endotélio/fisiopatologia , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/fisiopatologia , Humanos , Hospedeiro Imunocomprometido/imunologia , Infecções/imunologia , Infecções/fisiopatologia , Inflamação/imunologia , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Influenza Humana/fisiopatologia , Pandemias , Ativação Plaquetária , Agregação Plaquetária , Pneumonia/epidemiologia , Pneumonia/imunologia , Pneumonia/fisiopatologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Prognóstico , Fatores de Risco , Acidente Vascular Cerebral/imunologia , Trombose/epidemiologia , Trombose/imunologia , Infecção pelo Vírus da Varicela-Zoster/epidemiologia , Infecção pelo Vírus da Varicela-Zoster/imunologia , Infecção pelo Vírus da Varicela-Zoster/fisiopatologia
13.
Am J Cardiol ; 134: 83-90, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32892987

RESUMO

The optimal antiplatelet strategy after left atrial appendage (LAA) occlusion able to protect from device-related thrombosis, paying the lowest price in terms of bleeding increase, is unclear. In a real-world, observational study we performed a head-to-head comparison of single versus dual antiplatelet therapy (SAPT vs DAPT) in patients who underwent LAA occlusion. We included 610 consecutive patients, stratified according to the type of post-procedural antiplatelet therapy (280 on SAPT and 330 on DAPT). Primary outcome measure was the incidence of the net composite end point including Bleeding Academic Research Consortium classification 3-5 bleeding, major adverse cardiovascular events or device-related thrombosis at 1-year follow-up. The use of SAPT compared with DAPT was associated with similar incidence of the primary net composite end point (9.3% vs 12.7% p = 0.22), with an adjusted hazard ratio (HR) of 0.69, 95% confidence interval 0.41 to 1.15; p = 0.15) at multivariate analysis. However, SAPT significantly reduced Bleeding Academic Research Consortium classification 3-5 bleeding (2.9% vs 6.7%, p = 0.038; adjusted HR 0.37, 0.16 to 0.88; p = 0.024). The occurrence of ischemic events (major adverse cardiovascular events or device-related thrombosis) was not significantly different between the 2treatment strategies (7.8% vs 7.4%; adjusted HR 1.34, 0.70 to 2.55; p = 0.38). In patients who underwent LAA occlusion, post-procedural use of SAPT instead of DAPT was associated with reduction of bleeding complications, with no significant increase in the risk of thrombotic events. These hypothesis-generating findings should be confirmed in a specific, randomized study.


Assuntos
Apêndice Atrial/cirurgia , Fibrilação Atrial/cirurgia , Terapia Antiplaquetária Dupla/estatística & dados numéricos , Hemorragia/epidemiologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Implantação de Prótese , Acidente Vascular Cerebral/prevenção & controle , Trombose/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Aspirina/uso terapêutico , Fibrilação Atrial/complicações , Doenças Cardiovasculares/mortalidade , Clopidogrel/uso terapêutico , Embolia/etiologia , Embolia/prevenção & controle , Feminino , Humanos , Masculino , Modelos de Riscos Proporcionais , Dispositivo para Oclusão Septal , Acidente Vascular Cerebral/etiologia
14.
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
16.
Open Heart ; 7(2)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32938758

RESUMO

Risk factors for COVID-19 patients with poorer outcomes include pre-existing conditions: obesity, type 2 diabetes mellitus, cardiovascular disease (CVD), heart failure, hypertension, low oxygen saturation capacity, cancer, elevated: ferritin, C reactive protein (CRP) and D-dimer. A common denominator, hyperinsulinaemia, provides a plausible mechanism of action, underlying CVD, hypertension and strokes, all conditions typified with thrombi. The underlying science provides a theoretical management algorithm for the frontline practitioners.Vitamin D activation requires magnesium. Hyperinsulinaemia promotes: magnesium depletion via increased renal excretion, reduced intracellular levels, lowers vitamin D status via sequestration into adipocytes and hydroxylation activation inhibition. Hyperinsulinaemia mediates thrombi development via: fibrinolysis inhibition, anticoagulation production dysregulation, increasing reactive oxygen species, decreased antioxidant capacity via nicotinamide adenine dinucleotide depletion, haem oxidation and catabolism, producing carbon monoxide, increasing deep vein thrombosis risk and pulmonary emboli. Increased haem-synthesis demand upregulates carbon dioxide production, decreasing oxygen saturation capacity. Hyperinsulinaemia decreases cholesterol sulfurylation to cholesterol sulfate, as low vitamin D regulation due to magnesium depletion and/or vitamin D sequestration and/or diminished activation capacity decreases sulfotransferase enzyme SULT2B1b activity, consequently decreasing plasma membrane negative charge between red blood cells, platelets and endothelial cells, thus increasing agglutination and thrombosis.Patients with COVID-19 admitted with hyperglycaemia and/or hyperinsulinaemia should be placed on a restricted refined carbohydrate diet, with limited use of intravenous dextrose solutions. Degree/level of restriction is determined by serial testing of blood glucose, insulin and ketones. Supplemental magnesium, vitamin D and zinc should be administered. By implementing refined carbohydrate restriction, three primary risk factors, hyperinsulinaemia, hyperglycaemia and hypertension, that increase inflammation, coagulation and thrombosis risk are rapidly managed.


Assuntos
Infecções por Coronavirus/terapia , Dieta com Restrição de Carboidratos , Suplementos Nutricionais , Hiperinsulinismo/terapia , Insulina/sangue , Magnésio/uso terapêutico , Pneumonia Viral/terapia , Trombose/terapia , Vitamina D/uso terapêutico , Betacoronavirus/patogenicidade , Biomarcadores/sangue , Glicemia/metabolismo , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Suplementos Nutricionais/efeitos adversos , Interações Hospedeiro-Patógeno , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/epidemiologia , Cetonas/sangue , Magnésio/sangue , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Prognóstico , Fatores de Risco , Trombose/sangue , Trombose/epidemiologia , Trombose/virologia , Vitamina D/sangue , Zinco/uso terapêutico
17.
J Am Heart Assoc ; 9(21): e017773, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-32972320

RESUMO

Background Recent literature reports a strong thrombotic tendency in patients hospitalized for a coronavirus disease 2019 (COVID-19) infection. This characteristic is unusual and seems specific to COVID-19 infections, especially in their severe form. Viral infections can trigger acquired thrombophilia, which can then lead to thrombotic complications. We investigate for the presence of acquired thrombophilia, which could participate in this phenomenon, and report its prevalence. We also wonder if these thrombophilias participate in the bad prognosis of severe COVID-19 infections. Methods and Results In 89 consecutive patients hospitalized for COVID-19 infection, we found a 20% prevalence of PS (protein S) deficiency and a high (ie, 72%) prevalence of antiphospholipid antibodies: mainly lupus anticoagulant. The presence of PS deficiency or antiphospholipid antibodies was not linked with a prolonged activated partial thromboplastin time nor with D-dimer, fibrinogen, or CRP (C-reactive protein) concentrations. These coagulation abnormalities are also not linked with thrombotic clinical events occurring during hospitalization nor with mortality. Conclusions We assess a high prevalence of positive tests detecting thrombophilia in COVID-19 infections. However, in our series, these acquired thrombophilias are not correlated with the severity of the disease nor with the occurrence of thrombotic events. Albeit the strong thrombotic tendency in COVID-19 infections, the presence of frequent acquired thrombophilia may be part of the inflammation storm of COVID-19 and should not systematically modify our strategy on prophylactic anticoagulant treatment, which is already revised upwards in this pathological condition. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT04335162.


Assuntos
Síndrome Antifosfolipídica/epidemiologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Deficiência de Proteína S/epidemiologia , Trombose/epidemiologia , Idoso , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/diagnóstico , Biomarcadores/sangue , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Prevalência , Prognóstico , Proteína S/análise , Deficiência de Proteína S/sangue , Deficiência de Proteína S/diagnóstico , Fatores de Risco , Índice de Gravidade de Doença , Trombose/sangue , Trombose/diagnóstico
18.
Nat Med ; 26(10): 1609-1615, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32747830

RESUMO

Understanding the pathophysiology of SARS-CoV-2 infection is critical for therapeutic and public health strategies. Viral-host interactions can guide discovery of disease regulators, and protein structure function analysis points to several immune pathways, including complement and coagulation, as targets of coronaviruses. To determine whether conditions associated with dysregulated complement or coagulation systems impact disease, we performed a retrospective observational study and found that history of macular degeneration (a proxy for complement-activation disorders) and history of coagulation disorders (thrombocytopenia, thrombosis and hemorrhage) are risk factors for SARS-CoV-2-associated morbidity and mortality-effects that are independent of age, sex or history of smoking. Transcriptional profiling of nasopharyngeal swabs demonstrated that in addition to type-I interferon and interleukin-6-dependent inflammatory responses, infection results in robust engagement of the complement and coagulation pathways. Finally, in a candidate-driven genetic association study of severe SARS-CoV-2 disease, we identified putative complement and coagulation-associated loci including missense, eQTL and sQTL variants of critical complement and coagulation regulators. In addition to providing evidence that complement function modulates SARS-CoV-2 infection outcome, the data point to putative transcriptional genetic markers of susceptibility. The results highlight the value of using a multimodal analytical approach to reveal determinants and predictors of immunity, susceptibility and clinical outcome associated with infection.


Assuntos
Ativação do Complemento/imunologia , Infecções por Coronavirus/mortalidade , Hemorragia/epidemiologia , Degeneração Macular/epidemiologia , Pneumonia Viral/mortalidade , Trombocitopenia/epidemiologia , Trombose/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Coagulação Sanguínea/genética , Transtornos da Coagulação Sanguínea/epidemiologia , Ativação do Complemento/genética , Infecções por Coronavirus/sangue , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Expressão Gênica , Hemorragia/sangue , Hemorragia/imunologia , Doenças da Deficiência Hereditária de Complemento/epidemiologia , Doenças da Deficiência Hereditária de Complemento/imunologia , Humanos , Hipertensão/epidemiologia , Intubação Intratraqueal , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Obesidade/epidemiologia , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/genética , Pneumonia Viral/imunologia , Modelos de Riscos Proporcionais , Respiração Artificial , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Trombocitopenia/sangue , Trombose/sangue
19.
Eur J Vasc Endovasc Surg ; 60(5): 752-763, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32741678

RESUMO

OBJECTIVE: Radical excision of retroperitoneal or intra-abdominal soft tissue sarcomas may necessitate vessel resection and reconstruction. The aim of this study was to assess surgical results of retroperitoneal or intra-abdominal sarcomas involving major blood vessels. METHODS: This was a retrospective single centre cohort study and a comprehensive review of literature. Patients with retroperitoneal or intra-abdominal sarcomas treated by the oncovascular team in Helsinki University Hospital from 2010 to 2018 were reviewed for vascular and oncological outcomes. A comprehensive literature review of vascular reconstructions in patients with retroperitoneal sarcoma was performed. RESULTS: Vascular reconstruction was performed in 17 patients, 11 of whom required arterial reconstructions. Sixteen of the operations were sarcoma resections; the post-operative diagnosis for one patient was thrombosis instead of the presumed recurrent leiomyosarcoma. Early graft thrombosis occurred in two venous and one arterial reconstruction. Late thrombosis was detected in three (18%). The median follow up was 27 (range 0-82) months. Of the patients with sarcoma resections 5 (31%) died of sarcoma and further 4 (25%) developed local recurrence or new distant metastases. The comprehensive review of literature identified 37 articles with 110 patients, 89 of whom had inferior vena cava reconstruction only. Eight arterial reconstructions were described. Late graft thrombosis occurred in 14%. The follow up was 0-181 months, during which 57% remained disease free and 7% died of sarcoma. CONCLUSION: Vascular reconstructions enable radical resection of retroperitoneal and intra-abdominal sarcomas in patients with advanced disease. The complex operations are associated with an acceptable rate of serious peri-operative complications and symptomatic thrombosis of the repaired vessel is rare. However, further studies are needed to assess the performance of the vascular reconstructions in the long term.


Assuntos
Implante de Prótese Vascular/efeitos adversos , Oclusão de Enxerto Vascular/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Neoplasias Retroperitoneais/cirurgia , Sarcoma/cirurgia , Trombose/epidemiologia , Adulto , Idoso , Artérias/cirurgia , Implante de Prótese Vascular/métodos , Feminino , Seguimentos , Oclusão de Enxerto Vascular/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Complicações Pós-Operatórias/etiologia , Neoplasias Retroperitoneais/irrigação sanguínea , Neoplasias Retroperitoneais/patologia , Espaço Retroperitoneal/irrigação sanguínea , Espaço Retroperitoneal/cirurgia , Estudos Retrospectivos , Sarcoma/sangue , Sarcoma/patologia , Trombose/etiologia , Resultado do Tratamento , Grau de Desobstrução Vascular , Veia Cava Inferior/cirurgia
20.
Am J Cardiol ; 132: 106-113, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32773221

RESUMO

Leaflet thrombosis (LT) has been claimed as a potential cause of hemodynamic dysfunction or bioprosthetic valve degeneration of transcatheter heart valves. Sparse and contrasting evidence exists, however, regarding LT occurrence, prevention and treatment. MEDLINE, ISI Web of Science and SCOPUS databases were searched for studies published up to January 2020. Only studies reporting data on incidence and outcomes associated to the presence/absence of clinical or subclinical LT, detected or confirmed with a multidetector computed tomography exam were included. The study was designed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) requirements. Two reviewers independently screened articles for fulfillment of inclusion criteria. Data were pooled using a random-effect model. The primary end point was the incidence of LT. Secondary outcomes included: stroke and transient ischemic attacks and mean transvalvular gradients at different time-points in patients with and without LT. Of the initial 200 studies, 22 were finally included with a total of 11,567 patients. LT overall incidence was 8% (95% Confidence Interval [CI]: 5% to 13%, I2 = 96.4%). LT incidence in patients receiving only antiplatelets was 13% (95% CI: 7% to 23%, p <0.0001); patients discharged on oral anticoagulants had a reported incidence of 4% (95% CI: 2% to 8%, p <0.0001). Patients with LT, either clinical or subclinical, were not at increased risk of stroke (OR 1.06, 95% CI: 0.75 to 1.50, p = 0.730, I2 = 0.0%) or transient ischemic attacks (Odds Ratio 1.01, 95% CI: 0.40 to 2.57, p = 0.989, I2 = 0.0%). LT was associated with higher mean transvalvular gradients compared with patients without LT at 30 days post-transcatheter implantation, but not at discharge or at 1 year. LT is a relatively common event that, even when clinically manifest, is not associated with an increased risk of cerebrovascular events. Although patients on anticoagulants appear to be at lower risk of LT, the available evidence does not allow formulation of recommendations for prophylactical anticoagulation nor routine computed tomography after transcatheter aortic valve replacement.


Assuntos
Bioprótese/efeitos adversos , Cardiopatias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Sistema de Registros , Trombose/epidemiologia , Substituição da Valva Aórtica Transcateter/efeitos adversos , Estenose da Valva Aórtica/cirurgia , Saúde Global , Cardiopatias/etiologia , Humanos , Incidência , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Trombose/etiologia
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