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1.
J Hematol Oncol ; 14(1): 172, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34666811

RESUMO

BACKGROUND: Thromboembolism has been reported as a consequence of severe COVID-19. Although warfarin is a commonly used anticoagulant, it acts by antagonising vitamin K, which is low in patients with severe COVID-19. To date, the clinical evidence on the impact of regular use of warfarin on COVID-19-related thromboembolism is lacking. METHODS: On behalf of NHS England, we conducted a population-based cohort study investigating the association between warfarin and COVID-19 outcomes compared with direct oral anticoagulants (DOACs). We used the OpenSAFELY platform to analyse primary care data and pseudonymously linked SARS-CoV-2 antigen testing data, hospital admissions and death records from England. We used Cox regression to estimate hazard ratios (HRs) for COVID-19-related outcomes comparing warfarin with DOACs in people with non-valvular atrial fibrillation. We also conducted negative control outcome analyses (being tested for SARS-CoV-2 and non-COVID-19 death) to assess the potential impact of confounding. RESULTS: A total of 92,339 warfarin users and 280,407 DOAC users were included. We observed a lower risk of all outcomes associated with warfarin versus DOACs [testing positive for SARS-CoV-2, HR 0.73 (95% CI 0.68-0.79); COVID-19-related hospital admission, HR 0.75 (95% CI 0.68-0.83); COVID-19-related deaths, HR 0.74 (95% CI 0.66-0.83)]. A lower risk of negative control outcomes associated with warfarin versus DOACs was also observed [being tested for SARS-CoV-2, HR 0.80 (95% CI 0.79-0.81); non-COVID-19 deaths, HR 0.79 (95% CI 0.76-0.83)]. CONCLUSIONS: Overall, this study shows no evidence of harmful effects of warfarin on severe COVID-19 disease.


Assuntos
Anticoagulantes/uso terapêutico , COVID-19/epidemiologia , Tromboembolia/tratamento farmacológico , Tromboembolia/virologia , Varfarina/uso terapêutico , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/farmacologia , COVID-19/sangue , COVID-19/tratamento farmacológico , COVID-19/virologia , Estudos de Coortes , Inglaterra/epidemiologia , Humanos , Pessoa de Meia-Idade , SARS-CoV-2/isolamento & purificação , Tromboembolia/sangue , Tromboembolia/epidemiologia , Resultado do Tratamento , Adulto Jovem
2.
Cells ; 10(10)2021 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-34685567

RESUMO

Mesenchymal stem cells (MSCs) are multipotent adult stem cells present in virtually all tissues; they have a potent self-renewal capacity and can differentiate into multiple cell types. They also affect the ambient tissue by the paracrine secretion of numerous factors in vivo, including the induction of other stem cells' differentiation. In vitro, the culture media supernatant is named secretome and contains soluble molecules and extracellular vesicles that retain potent biological function in tissue regeneration. MSCs are considered safe for human treatment; their use does not involve ethical issues, as embryonic stem cells do not require genetic manipulation as induced pluripotent stem cells, and after intravenous injection, they are mainly found in the lugs. Therefore, these cells are currently being tested in various preclinical and clinical trials for several diseases, including COVID-19. Several affected COVID-19 patients develop induced acute respiratory distress syndrome (ARDS) associated with an uncontrolled inflammatory response. This condition causes extensive damage to the lungs and may leave serious post-COVID-19 sequelae. As the disease may cause systemic alterations, such as thromboembolism and compromised renal and cardiac function, the intravenous injection of MSCs may be a therapeutic alternative against multiple pathological manifestations. In this work, we reviewed the literature about MSCs biology, focusing on their function in pulmonary regeneration and their use in COVID-19 treatment.


Assuntos
COVID-19/sangue , COVID-19/terapia , Pulmão/fisiologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Regeneração/fisiologia , Animais , COVID-19/tratamento farmacológico , Diferenciação Celular , Terapia Baseada em Transplante de Células e Tecidos , Meios de Cultura , Vesículas Extracelulares , Humanos , Inflamação , Camundongos , Camundongos SCID , Fenótipo , Pneumonia/sangue , Pneumonia/imunologia , Pneumonia/terapia , Síndrome do Desconforto Respiratório , SARS-CoV-2 , Tromboembolia/sangue , Tromboembolia/imunologia , Tromboembolia/terapia
3.
Clin Appl Thromb Hemost ; 27: 10760296211051712, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34714177

RESUMO

BACKGROUND: Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic, there have been many reports of increased incidence of venous thromboembolism and arterial events as a complication. OBJECTIVE: To determine the incidence of symptomatic thrombotic events (TEs) in patients hospitalized for SARS-CoV2 disease (coronavirus 19 [Covid-19]). METHODS: A retrospective single-center cohort study with adult patients with a positive reverse transcriptase-polymerase chain reaction (rt-PCR) for SARS-CoV2, included from the date of diagnosis of Covid-19 and followed for 90 days or until death. RESULTS: A total of 1621 patients were included in this study. The median age was 73 years (interquartile range25th-75th [IQR] 53-87 years) and 57% (913) were female. Overall mortality was 21.6% (348). The overall incidence of symptomatic TEs within 90 days of diagnosis was 1.8% (30 of 1621) occurring in 28 patients, including an incidence of pulmonary embolism of 0.9% (15, 95% confidence interval [CI] 0.60%-1.6%), deep venous thrombosis of 0.61% (10, 95% CI 0.2%-1%), ischemic stroke of 0.25% (4, 95% CI 0.09%-0.65%), and ischemic arterial events of 0.06% (1, 95% CI 0.008%-0.43%). No acute coronary syndrome events were recorded. The incidence of symptomatic TEs was significantly lower in the general ward than in intensive care units (1.2% vs 5.7%; p < .001). The median time since positive rt-PCR for SARS-CoV2 to symptomatic TE was 22.5 days (IQR 19-43 days). There was no significant difference in the proportion of patients receiving (53.6%) and not receiving thromboprophylaxis (66.5%) and the development of TEs. CONCLUSION: The overall incidence of symptomatic TEs among these patients was lower than the incidence previously reported.


Assuntos
Arteriopatias Oclusivas/epidemiologia , COVID-19/epidemiologia , Embolia Pulmonar/epidemiologia , Tromboembolia/epidemiologia , Trombose Venosa/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Argentina/epidemiologia , Arteriopatias Oclusivas/sangue , Arteriopatias Oclusivas/diagnóstico , COVID-19/sangue , COVID-19/diagnóstico , Feminino , Humanos , Incidência , AVC Isquêmico/sangue , AVC Isquêmico/diagnóstico , AVC Isquêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico , Estudos Retrospectivos , Tromboembolia/sangue , Tromboembolia/diagnóstico , Fatores de Tempo , Trombose Venosa/sangue , Trombose Venosa/diagnóstico
4.
Cancer Sci ; 112(11): 4679-4691, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34382298

RESUMO

Pancreatic cancer frequently involves cancer-associated thromboembolism, which is strongly associated with poor prognosis. Tissue factor, a blood coagulation factor largely produced in cancer patients as a component of extracellular vesicles, plays a key role in the incidence of cancer-associated thromboembolism in patients with pancreatic cancer. However, no prospective studies have been published on the relationship between tissue factor and cancer-associated thromboembolism or patient clinical characteristics, including recent chemotherapy regimens. Thus, we aimed to address this in a Japanese cohort of 197 patients and 41 healthy volunteers. Plasma tissue factor levels were measured by ELISAs preevaluated by tissue factor specificity. Multivariable analysis was used to identify independent predictors of cancer-associated thromboembolism. We found that the cancer-associated thromboembolism rate in the patient cohort was 6.6% (4.6%, venous thromboembolism; 2.0%, arterial thromboembolism). Tissue factor levels of 100 pg/mL or higher at patient registration were predictive of cancer-associated thromboembolism, with positive and negative predictive values of 23.1% and 94.6%, respectively. Multivariable analysis showed that plasma tissue factor levels were an independent predictive factor for cancer-associated thromboembolism, with a risk ratio of 5.54 (95% confidence interval, 1.02-30.09). Unlike in healthy volunteers and patients without cancer-associated thromboembolism, tissue factor levels were highly correlated with extracellular vesicles' procoagulant activity in patients developing cancer-associated thromboembolism. Taken together, our data show that the tissue factor levels at patient registration were a predictive factor for cancer-associated thromboembolism in this cohort of patients with pancreatic cancer.


Assuntos
Neoplasias Pancreáticas/complicações , Tromboembolia/etiologia , Tromboplastina/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Intervalos de Confiança , Ensaio de Imunoadsorção Enzimática/métodos , Vesículas Extracelulares , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/tratamento farmacológico , Valor Preditivo dos Testes , Risco , Tromboembolia/sangue , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia
5.
Sci Rep ; 11(1): 16648, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404824

RESUMO

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) supports patients suffering from refractory cardiogenic shock. Thromboembolic complications (TeC) are common in VA-ECMO patients and are associated with increased morbidity and mortality. Valid markers to predict TeC in VA-ECMO patients are lacking. The present study investigated the predictive value of baseline Fibrinogen-Albumin-Ratio (FAR) for in-hospital TeC in patients undergoing VA-ECMO. This retrospective cohort study included patients who underwent VA-ECMO therapy due to cardiogenic shock at the University Hospital Duesseldorf, Germany between 2011 and 2018. Main exposure was baseline FAR measured at initiation of VA-ECMO therapy. The primary endpoint was the in-hospital incidence of TeC. In total, 344 patients were included into analysis (74.7% male, mean age 59 ± 14 years). The in-hospital incidence of TeC was 34%. Receiver operating characteristics (ROC) curve of FAR for in-hospital TeC revealed an area under the curve of 0.67 [95% confidence interval (CI) 0.61-0.74]. Youden index determined a cutoff of 130 for baseline FAR. Multivariate logistic regression revealed an adjusted odds-ratio of 3.72 [95% CI 2.26-6.14] for the association between FAR and TeC. Baseline FAR is independently associated with in-hospital TeC in patients undergoing VA-ECMO. Thus, FAR might contribute to the prediction of TeC in this cohort.


Assuntos
Albuminas/metabolismo , Oxigenação por Membrana Extracorpórea , Fibrinogênio/metabolismo , Tromboembolia/sangue , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
Biomed Res Int ; 2021: 2013371, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34435041

RESUMO

Background: This study was aimed at revealing neuroimaging findings in COVID-19 patients and at discussing their relationship with epidemiological data and some laboratory parameters. Materials and Method. This study included 436 cases of COVID-19 and 40 cases of non-COVID-19 acute/subacute thromboembolism who underwent at least one neuroimaging procedure due to neurological symptoms between April 2020 and December 2020. The group of COVID-19-positive acute/subacute thromboembolism cases was compared with both the group of normal brain imaging cases and the non-COVID-19 acute/subacute thromboembolism group in terms of demographic data and laboratory parameters. Results: When the acute/subacute thromboembolism group and neuroimaging findings were compared in terms of negative group, presence of comorbid disease, D-dimer level, and lymphocyte count in COVID-19 patients, a statistically significant difference was found (p = 0.047, 0.014, and <0.001, respectively). COVID-19-positive and COVID-19-negative acute/subacute thromboembolism cases that were compared in terms of gender, neuroimaging reason, C-reactive protein, D-dimer level and lymphocyte count, a statistically significant difference was found (p = 0.003, <0.001, 0.005, 0.02, and <0.001, respectively). Conclusion: Acute thromboembolic events are common in patients with COVID-19 due to a potentially increased procoagulant process. Neurological evaluation and, if necessary, detailed neuroimaging should be performed, especially in cases with high D-dimer levels.


Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico por imagem , Neuroimagem/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , COVID-19/sangue , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Lobo Occipital/diagnóstico por imagem , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Tromboembolia/sangue , Tromboembolia/diagnóstico por imagem , Adulto Jovem
7.
Expert Opin Drug Saf ; 20(11): 1451-1453, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34264151

RESUMO

Introduction: Concerns about the increased risk of blood clots associated with the VAXZEVRIA (previously named Oxford-AstraZeneca COVID-19 vaccine) and Johnson & Johnson (Janssen) COVID-19 vaccines raises the question of the thrombotic safety of other COVID-19 vaccines such as Pfizer-BioNTech or Moderna, especially in younger women, who at the early stage of the pandemic was a priority group for vaccination. Methods: Using the US-based Vaccine Adverse Event Reporting System (VAERS) and the FDA Event Reporting System (FAERS), we retrieved cases of thrombosis following vaccinations or hormonal contraceptive use in women aged ≤ 50 years. We used the reporting odds ratio (ROR) as a disproportionality measure. Results: On 19 March 2021, out of 13.6 million women aged ≤ 50 exposed to at least one dose of Pfizer-BioNTech or Moderna COVID-19 vaccines in the US, only 61 cases were reported with a total of 68 thromboembolic events (1 case per 222,951 vaccinated). None of the thromboembolic events included in our analysis were disproportionally reported for the two COVID-19 vaccines. Conclusion: Our results do support that, when compared to hormonal contraceptive use, the mRNA vaccines do not show disproportional reporting of thromboembolic events in younger women.


Assuntos
Vacinas contra COVID-19/efeitos adversos , Tromboembolia/sangue , Vacinação/efeitos adversos , Sistemas de Notificação de Reações Adversas a Medicamentos , Fatores Etários , Vacinas contra COVID-19/administração & dosagem , Anticoncepcionais Orais Hormonais/efeitos adversos , Feminino , Contracepção Hormonal/efeitos adversos , Humanos , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Fatores Sexuais , Tromboembolia/diagnóstico , Tromboembolia/epidemiologia , Resultado do Tratamento
8.
Biomed Res Int ; 2021: 6634417, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33959659

RESUMO

Background: MicroRNAs (miRNAs) play an important role in the pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH). However, the potential correlation between miRNA expression and the severity of CTEPH remains unclear. Our previous study indicated that miRNAs hsa-let-7b-3p, hsa-miR-17-5p, hsa-miR-106b-5p, hsa-miR-3202, hsa-miR-665, and hsa-miR-93-5p are closely involved in CTEPH. This study assessed the associations between the expression levels of these miRNAs and clinical parameters in CTEPH patients. Methods: A total of eight CTEPH patients and eight healthy adults as a reference group were included, and clinical data including total protein (TP), albumin (Alb), lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), uric acid (UA), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were collected. Right heart catheterization was conducted to obtain hemodynamic data including cardiac index (CI). The expression levels of let-7b-3p, miR-17-5p, miR-106b-5p, miR-3202, miR-665, and miR-93-5p were measured by quantitative real-time PCR (qPCR). Correlation analysis was applied to estimate the associations between miRNA expression levels and clinical parameters in CTEPH patients. Results: Serum TP and Alb levels were decreased, while LDH, HBDH, and UA levels were increased in CTEPH patients compared with the reference group (P < 0.05). miR-3202 and miR-665 were upregulated, whereas let-7b-3p, miR-17-5p, miR-106b-5p, and miR-93-5p were downregulated in CTEPH patients relative to the reference group (P < 0.05). miR-93-5p expression was positively correlated with NT-proBNP level and negatively correlated with CI (P < 0.05). Moreover, let-7b-3p tended to be positively correlated with mean pulmonary arterial pressure. Conclusions: miR-93-5p expression was associated with the severity of CTEPH and could act as a potential predictor of high-risk CTEPH.


Assuntos
Hipertensão Pulmonar , MicroRNAs , Tromboembolia , Idoso , Biomarcadores/análise , Biomarcadores/metabolismo , Feminino , Humanos , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/metabolismo , Masculino , MicroRNAs/sangue , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Tromboembolia/sangue , Tromboembolia/genética , Tromboembolia/metabolismo
9.
J Thromb Thrombolysis ; 52(2): 542-552, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33973157

RESUMO

Coronavirus 2019 disease (COVID-19) is associated with coagulation dysfunction that predisposes patients to an increased risk for both arterial (ATE) and venous thromboembolism (VTE) and consequent poor prognosis; in particular, the incidence of ATE and VTE in critically ill COVID-19 patients can reach 5% and 31%, respectively. The mechanism of thrombosis in COVID-19 patients is complex and still not completely clear. Recent literature suggests a link between the presence of antiphospholipid antibodies (aPLs) and thromboembolism in COVID-19 patients. However, it remains uncertain whether aPLs are an epiphenomenon or are involved in the pathogenesis of the disease.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Tromboembolia/imunologia , Animais , Anticorpos Antifosfolipídeos/sangue , Coagulação Sanguínea , COVID-19/sangue , COVID-19/complicações , Estado Terminal , Humanos , Tromboembolia/sangue , Tromboembolia/complicações , Tromboembolia Venosa/sangue , Tromboembolia Venosa/complicações , Tromboembolia Venosa/imunologia
10.
J Thromb Thrombolysis ; 52(3): 772-778, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33844150

RESUMO

It is still debated whether prophylactic doses of low-molecular- weight heparin (LMWH) are always effective in preventing Venous Thromboembolism (VTE) and mortality in COVID-19. Furthermore, there is paucity of data for those patients not requiring ventilation. We explored mortality and the safety/efficacy profile of LMWH in a cohort of Italian patients with COVID-19 who did not undergo ventilation. From the initial cohort of 422 patients, 264 were enrolled. Most (n = 156, 87.7%) received standard LMWH prophylaxis during hospitalization, with no significant difference between medical wards and Intensive Care Unit (ICU). Major or not major but clinically relevant hemorrhages were recorded in 13 (4.9%) patients: twelve in those taking prophylactic LMWH and one in a patient taking oral anticoagulants (p: n.s.). Thirty-nine patients (14.8%) with median age 75 years. were transfused. Hemoglobin (Hb) at admission was significantly lower in transfused patients and Hb at admission inversely correlated with the number of red blood cells units transfused (p < 0.001). In-hospital mortality occurred in 76 (28.8%) patients, 46 (24.3%) of whom admitted to medical wards. Furthermore, Hb levels at admittance were significantly lower in fatalities (g/dl 12.3; IQR 2.4 vs. 13.3; IQR 2.8; Mann-Whitney U-test; p = 0.001). After the exclusion of patients treated by LMWH intermediate or therapeutic doses (n = 32), the logistic regression showed that prophylaxis significantly and independently reduced mortality (OR 0.31, 95% CI 0.13-0.85). Present data show that COVID-19 patients who do not require ventilation benefit from prophylactic doses of LMWH.


Assuntos
Anticoagulantes/uso terapêutico , Transfusão de Sangue , COVID-19/terapia , Heparina de Baixo Peso Molecular/uso terapêutico , Tromboembolia/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Transfusão de Sangue/mortalidade , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/mortalidade , Tomada de Decisão Clínica , Feminino , Heparina de Baixo Peso Molecular/efeitos adversos , Mortalidade Hospitalar , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Proteção , Medição de Risco , Fatores de Risco , Tromboembolia/sangue , Tromboembolia/diagnóstico , Tromboembolia/mortalidade , Fatores de Tempo , Resultado do Tratamento
11.
Toxins (Basel) ; 13(3)2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33803899

RESUMO

Patients with chronic kidney disease (CKD) are at an increased risk of thromboembolic complications, including myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism. These complications lead to increased mortality. Evidence points to the key role of CKD-associated dysbiosis and its effect via the generation of gut microbial metabolites in inducing the prothrombotic phenotype. This phenomenon is known as thrombolome, a panel of intestinal bacteria-derived uremic toxins that enhance thrombosis via increased tissue factor expression, platelet hyperactivity, microparticles release, and endothelial dysfunction. This review discusses the role of uremic toxins derived from gut-microbiota metabolism of dietary tryptophan (indoxyl sulfate (IS), indole-3-acetic acid (IAA), kynurenine (KYN)), phenylalanine/tyrosine (p-cresol sulfate (PCS), p-cresol glucuronide (PCG), phenylacetylglutamine (PAGln)) and choline/phosphatidylcholine (trimethylamine N-oxide (TMAO)) in spontaneously induced thrombosis. The increase in the generation of gut microbial uremic toxins, the activation of aryl hydrocarbon (AhRs) and platelet adrenergic (ARs) receptors, and the nuclear factor kappa B (NF-κB) signaling pathway can serve as potential targets during the prevention of thromboembolic events. They can also help create a new therapeutic approach in the CKD population.


Assuntos
Bactérias/metabolismo , Coagulação Sanguínea , Microbioma Gastrointestinal , Intestinos/microbiologia , Insuficiência Renal Crônica/complicações , Tromboembolia/etiologia , Toxinas Biológicas/sangue , Uremia/complicações , Animais , Disbiose , Humanos , Prognóstico , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/microbiologia , Fatores de Risco , Tromboembolia/sangue , Tromboembolia/microbiologia , Uremia/sangue , Uremia/microbiologia
12.
Clin Appl Thromb Hemost ; 27: 10760296211010976, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33926262

RESUMO

The prognostic role of hypercoagulability in COVID-19 patients is ambiguous. D-dimer, may be regarded as a global marker of hemostasis activation in COVID-19. Our study was to assess the predictive value of D-dimer for the severity, mortality and incidence of venous thromboembolism (VTE) events in COVID-19 patients. PubMed, EMBASE, Cochrane Library and Web of Science databases were searched. The pooled diagnostic value (95% confidence interval [CI]) of D-dimer was evaluated with a bivariate mixed-effects binary regression modeling framework. Sensitivity analysis and meta regression were used to determine heterogeneity and test robustness. A Spearman rank correlation tested threshold effect caused by different cut offs and units in D-dimer reports. The pooled sensitivity of the prognostic performance of D-dimer for the severity, mortality and VTE in COVID-19 were 77% (95% CI: 73%-80%), 75% (95% CI: 65%-82%) and 90% (95% CI: 90%-90%) respectively, and the specificity were 71% (95% CI: 64%-77%), 83% (95% CI: 77%-87%) and 60% (95% CI: 60%-60%). D-dimer can predict severe and fatal cases of COVID-19 with moderate accuracy. It also shows high sensitivity but relatively low specificity for detecting COVID-19-related VTE events, indicating that it can be used to screen for patients with VTE.


Assuntos
Teste para COVID-19 , COVID-19 , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , SARS-CoV-2/metabolismo , Tromboembolia , COVID-19/sangue , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Masculino , Valor Preditivo dos Testes , Taxa de Sobrevida , Tromboembolia/sangue , Tromboembolia/diagnóstico , Tromboembolia/etiologia , Tromboembolia/mortalidade
13.
Front Endocrinol (Lausanne) ; 12: 651009, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33859620

RESUMO

Introduction: Patients with severe COVID-19 infections have coagulation abnormalities indicative of a hypercoagulable state, with thromboembolic complications and increased mortality. Platelets are recognized as mediators of inflammation, releasing proinflammatory and prothrombotic factors, and are hyperactivated in COVID-19 infected patients. Activated platelets have also been reported in type 2 diabetes (T2D) patients, putting these patients at higher risk for thromboembolic complications of COVID-19 infection. Methods: A case-control study of T2D (n=33) and control subjects (n=30) who underwent a hyperinsulinemic clamp to induce normoglycemia in T2D subjects: T2D: baseline glucose 7.5 ± 0.3mmol/l (135.1 ± 5.4mg/dl), reduced to 4.5 ± 0.07mmol/l (81 ± 1.2mg/dl) with 1-hour clamp; Controls: maintained at 5.1 ± 0.1mmol/l (91.9 ± 1.8mg/dl). Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was used to determine a panel of platelet proteins. Results: Prothrombotic platelet proteins were elevated in T2D versus controls: platelet factor 4 (PF4, p<0.05); platelet glycoprotein VI (PGVI p<0.05); P-selectin (p<0.01) and plasminogen activator inhibitor I (PAI-1, p<0.01). In addition, the antithrombotic platelet-related proteins, plasmin (p<0.05) and heparin cofactor II (HCFII, p<0.05), were increased in T2D. Normalization of glucose in the T2D cohort had no effect on platelet protein levels. Conclusion: T2D patients have platelet hyperactivation, placing them at higher risk for thromboembolic events. When infected with COVID-19, this risk may be compounded, and their propensity for a more severe COVID-19 disease course increased. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03102801, identifier NCT03102801.


Assuntos
Transtornos Plaquetários/sangue , Transtornos Plaquetários/etiologia , Plaquetas/química , Proteínas Sanguíneas/análise , COVID-19/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Hipoglicemia/sangue , Hipoglicemia/complicações , Idoso , COVID-19/complicações , Estudos de Casos e Controles , Feminino , Técnica Clamp de Glucose , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária , Tromboembolia/sangue , Tromboembolia/etiologia
14.
J Thromb Thrombolysis ; 52(3): 914-924, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33730303

RESUMO

In this study, we investigated whether the CHA2DS2-VASc score could be used to estimate the need for hospitalization in the intensive care unit (ICU), the length of stay in the ICU, and mortality in patients with COVID-19. Patients admitted to Merkezefendi State Hospital because of COVID-19 diagnosis confirmed by RNA detection of virus by using polymerase chain reaction between March 24, 2020 and July 6, 2020, were screened retrospectively. The CHA2DS2-VASc and modified CHA2DS2-VASc score of all patients was calculated. Also, we received all patients' complete biochemical markers including D-dimer, Troponin I, and c-reactive protein on admission. We enrolled 1000 patients; 791 were admitted to the general medical service and 209 to the ICU; 82 of these 209 patients died. The ROC curves of the CHA2DS2-VASc and M-CHA2DS2-VASc scores were analyzed. The cut-off values of these scores for predicting mortality were ≥ 3 (2 or under and 3). The CHA2DS2-VASc and M-CHA2DS2-VASc scores had an area under the curve value of 0.89 on the ROC. The sensitivity and specificity of the CHA2DS2-VASc scores were 81.7% and 83.8%, respectively; the sensitivity and specificity of the M-CHA2DS2-VASc scores were 85.3% and 84.1%, respectively. Multivariate logistic regression analysis showed that CHA2DS2-VASc, Troponin I, D-Dimer, and CRP were independent predictors of mortality in COVID-19 patients. Using a simple and easily available scoring system, CHA2DS2-VASc and M-CHA2DS2-VASc scores can be assessed in patients diagnosed with COVID-19. These scores can predict mortality and the need for ICU hospitalization in these patients.


Assuntos
COVID-19/diagnóstico , Técnicas de Apoio para a Decisão , Mortalidade Hospitalar , Hospitalização , Unidades de Terapia Intensiva , Tromboembolia/diagnóstico , Adolescente , Adulto , Idoso , Biomarcadores/sangue , COVID-19/sangue , COVID-19/mortalidade , COVID-19/terapia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Receptores Imunológicos/análise , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Tromboembolia/sangue , Tromboembolia/mortalidade , Tromboembolia/terapia , Fatores de Tempo , Troponina I/sangue , Turquia , Adulto Jovem
15.
J Neurointerv Surg ; 13(7): 594-598, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33722963

RESUMO

BACKGROUND: We retrospectively evaluated the composition of retrieved clots from ischemic stroke patients to study the association between histological composition and stroke etiology METHODS: Consecutive patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using martius scarlet blue (MSB) staining, and quantification for red blood cells (RBCs), white blood cells (WBCs), fibrin and platelets was performed using Orbit Image Software. A Wilcoxon test was used for continuous variables and χ2 test for categorical variables. RESULTS: 1350 patients were included in this study. The overall rate of Thrombolysis In Cerebral Infarction (TICI) 2c/3 was 68%. 501 patients received tissue plasminogen activator (tPA) (37%). 267 patients (20%) had a large artery atherosclerosis (LAA) source, 662 (49%) a cardioembolic (CE) source, 301 (22%) were cryptogenic, and the remainder had other identifiable sources including hypercoagulable state or dissection. LAA thrombi had a higher mean RBC density (46±23% vs 42±22%, p=0.01) and a lower platelet density (24±18% vs 27±18%, p=0.03) than CE thrombi. Clots from dissection patients had the highest mean RBC density (50±24%) while clots from patients with a hypercoagulable state had the lowest mean RBC density (26±21%). CONCLUSIONS: Our study found statistically significant but clinically insignificant differences between clots of CE and LAA etiologies. Future studies should emphasize molecular, proteomic and immunohistochemical characteristics to determine links between clot composition and etiology.


Assuntos
Eritrócitos , Sistema de Registros , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Tromboembolia/cirurgia , Trombose/cirurgia , Idoso , Idoso de 80 Anos ou mais , Eritrócitos/química , Feminino , Fibrina/análise , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico por imagem , Tromboembolia/sangue , Tromboembolia/diagnóstico por imagem , Trombose/sangue , Trombose/diagnóstico por imagem , Ativador de Plasminogênio Tecidual/administração & dosagem , Ativador de Plasminogênio Tecidual/análise , Ativador de Plasminogênio Tecidual/sangue
16.
J Thromb Thrombolysis ; 52(3): 782-790, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33649979

RESUMO

A pro-thrombotic milieu and a higher risk of thrombotic events were observed in patients with CoronaVirus disease-19 (COVID-19). Accordingly, recent data suggested a beneficial role of low molecular weight heparin (LMWH), but the optimal dosage of this treatment is unknown. We evaluated the association between prophylactic vs. intermediate-to-fully anticoagulant doses of enoxaparin and in-hospital adverse events in patients with COVID-19. We retrospectively included 436 consecutive patients admitted in three Italian hospitals. Outcome according to the use of prophylactic (4000 IU) vs. higher (> 4000 IU) daily dosage of enoxaparin was evaluated. The primary end-point was in-hospital death. Secondary outcome measures were in-hospital cardiovascular death, venous thromboembolism, new-onset acute respiratory distress syndrome (ARDS) and mechanical ventilation. A total of 287 patients (65.8%) were treated with the prophylactic enoxaparin regimen and 149 (34.2%) with a higher dosing regimen. The use of prophylactic enoxaparin dose was associated with a similar incidence of all-cause mortality (25.4% vs. 26.9% with the higher dose; OR at multivariable analysis, including the propensity score: 0.847, 95% CI 0.400-0.1.792; p = 0.664). In the prophylactic dose group, a significantly lower incidence of cardiovascular death (OR 0.165), venous thromboembolism (OR 0.067), new-onset ARDS (OR 0.454) and mechanical intubation (OR 0.150) was observed. In patients hospitalized for COVID-19, the use of a prophylactic dosage of enoxaparin appears to be associated with similar in-hospital overall mortality compared to higher doses. These findings require confirmation in a randomized, controlled study.


Assuntos
Anticoagulantes/administração & dosagem , COVID-19/terapia , Enoxaparina/administração & dosagem , Hospitalização , Tromboembolia/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/mortalidade , Enoxaparina/efeitos adversos , Feminino , Mortalidade Hospitalar , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Fatores de Proteção , Respiração Artificial , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Tromboembolia/sangue , Tromboembolia/diagnóstico , Tromboembolia/mortalidade , Fatores de Tempo , Resultado do Tratamento
17.
High Blood Press Cardiovasc Prev ; 28(3): 271-282, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33742366

RESUMO

INTRODUCTION: The role of anticoagulation in octogenarians and nonagenarians with atrial fibrillation (AF) is controversial due to the lack of evidence from randomized controlled trials (RCTs), owing to the under representation of these patients in clinical trials. AIM: In the present meta-analysis we aim at comparing the clinical benefits and risk of anticoagulation (AC) with no AC in octogenarians and nonagenarians. METHODS: We systematically searched MEDLINE/PubMed, EMBASE/Ovid, and Web of Science databases from the inception to October, 2020. Studies were eligible for inclusion if they met the following criteria: studies comparing AC with no AC in patients aged 80 or more for AF and reported thromboembolic events (TE) and bleeding outcomes. We used Mantel-Haenszel method with a Paule-Mandel estimator of Tau2 with Hartung Knapp-Sidik-Jonkman adjustment to estimate risk ratio (RR) with a 95% confidence interval (CI). Outlier analysis was used to adjust for statistical heterogeneity. RESULTS: A total of 10 observation studies and 1 RCT were included in the final analysis. There was no difference in the risk of TE with AC in octogenarians and nonagenarians compared with no AC, before [RR: 0.87, 95% CI 0.62-1.23, I2: 71%, GRADE confidence "very low"] and after [RR: 0.83, 95% CI 0.66-1.04, I2: 55.5%] adjusting for statistical heterogeneity among studies. In the unadjusted analysis, no difference in the risk of bleeding events was observed between both groups [RR: 1.05, 95% CI 0.62-1.77, I2: 86%, GRADE confidence "very low"]. After adjusting for heterogeneity, AC was associated with an increased risk of bleeding compared with those not receiving AC [RR: 1.57, 95% CI 1.44-1.71, I2: 0%]. AC in octogenarians was not associated with a net clinical benefit compared with no AC. CONCLUSIONS: This meta-analysis did not demonstrate any difference in the risk TE in octogenarians and nonagenarians with AF on AC vs. no AC, in both the adjusted and unadjusted analyses. Also, the risk of bleeding events in the unadjusted analysis was similar between both groups. The adjusted analysis showed an increased risk of bleeding in the AC group compared with no AC group. More data is needed to establish safety and efficacy of AC in this vulnerable patient population. The results of this analysis should be interpreted with caution due to the observational nature of most studies included, and the only RCT reported lower rates of TE and similar risk of bleeding.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Fatores Etários , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Fibrilação Atrial/sangue , Coagulação Sanguínea/efeitos dos fármacos , Hemorragia/induzido quimicamente , Humanos , Fatores de Risco , Tromboembolia/sangue
18.
J Clin Endocrinol Metab ; 106(8): e3078-e3086, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-33705547

RESUMO

CONTEXT: An association was recently reported between genetic markers related to high testosterone and increased risk of thromboembolism in men, but a possible causal role of estradiol for risk of thromboembolism in men remains unknown. OBJECTIVE: This work aimed to determine whether endogenous estradiol has a causal role in thromboembolism in men. METHODS: A 2-sample mendelian randomization study using gene-based genetic instruments assessed the association between endogenous estradiol genetically predicted by 22 variants in the aromatase CYP19A1 gene region and the risk of thromboembolism (5815 cases) in 170 593 unrelated men of White ancestry in the UK Biobank. The main outcome measure included thromboembolism based on self-reports, hospital episodes, and death. RESULTS: Endogenous estradiol genetically predicted by variants in the CYP19A1 gene region was inversely associated with the risk of thromboembolism (odds ratio per SD increase in estradiol 0.74; 95% CI, 0.62-0.90). In contrast, genetic variants in the JMJD1C gene, used as a predictor of high endogenous testosterone, were associated with an increased risk of thromboembolism (odds ratio per SD increase in testosterone 1.39; 95% CI, 1.12-1.72). Subsequent explorative analyses evaluating potential repercussions of thromboembolism revealed that endogenous estradiol genetically predicted by variants in the CYP19A1 gene region was inversely associated with the risk of ischemic stroke (0.68; 95% CI, 0.49-0.95) but not myocardial infarction (0.97; 95% CI, 0.84-1.13). CONCLUSION: Genetically predicted estradiol was inversely associated with the risk of thromboembolism and ischemic stroke in men. The ratio between testosterone and estradiol, determined by CYP19A1 activity, may contribute to the overall impact of sex steroids on thromboembolism in men.


Assuntos
Aromatase/genética , Estradiol/sangue , Polimorfismo de Nucleotídeo Único , Tromboembolia/genética , Idoso , Estudos de Associação Genética , Humanos , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Testosterona/sangue , Tromboembolia/sangue
19.
Clin Appl Thromb Hemost ; 27: 1076029620985941, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33529054

RESUMO

Our study aimed to investigate the levels and time-course of systemic inflammatory and hemostasis markers in the early postoperative period in patients undergoing total hip replacement (THR). The study included 70 patients of both sexes, average age 68.4 ± 10.9 years. Levels of inflammatory and hemostasis markers were measured before surgery (POD 0), a day after the surgery (POD 1) and 5 days after surgery (POD 5). In the postoperative period inflammatory markers increased. The operation provoked a significant increase of CRP on POD 1 in comparison to POD 0 (68.5 ± 5.4 vs 6.8 ± 2.2 µg/mL, p < 0.001) and the additional increase was registered on POD 5 (87.5 ± 8.1 vs 68.5 ± 5.4 µg/mL, p < 0.001). Interleukin-6 significantly increased on POD 1 (251.5 ± 21.6 vs 14.6 ± 7.1 µg/mL, p < 0.001) and after that (POD 5) decreased. After surgery leukocyte count, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio were significantly higher compared to POD 0. Activation of coagulation in the postoperative period was shown by increased peak thrombin on POD 5 in comparison to POD 0 (185 ± 27 vs. 124 ± 31 nM, p < 0.001). D-dimer was increased on POD 1 and an additional rise was observed on POD 5. vWF also progressively increased in the observed period. Results of our study showed that after THR systemic inflammatory markers increased and coagulation function was enhanced. Determination of inflammatory and procoagulant markers could help identify patients at risk for cardiovascular thromboembolic events.


Assuntos
Artroplastia de Quadril , Fatores de Coagulação Sanguínea/metabolismo , Mediadores da Inflamação/sangue , Idoso , Artroplastia de Quadril/efeitos adversos , Biomarcadores/sangue , Coagulação Sanguínea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Tromboembolia/sangue , Tromboembolia/etiologia , Fatores de Tempo , Resultado do Tratamento
20.
Nutr Metab Cardiovasc Dis ; 31(3): 860-868, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33549449

RESUMO

BACKGROUND AND AIMS: Oral anticoagulation is effective for stroke prevention in atrial fibrillation (AF). However, strokes may still occur in high-risk individuals. We conducted a prospective trial to assess the association between adipocytokine serum levels and surrogate parameters for thromboembolic events. METHODS AND RESULTS: In this cross-sectional multicenter trial, we enrolled 189 patients with AF who were on oral anticoagulation. The primary endpoint was defined as either the presence of spontaneous echo contrast (SEC), a left atrial appendage (LAA), or a left atrial (LA) thrombus on transesophageal echocardiography. We investigated the association of adipocytokine serum levels with the combined endpoint using logistic regression analysis. Forty-eight individuals (25%) were assigned to group 1 (G1) due to the occurrence of at least one of the components of the combined endpoint (41 [21.7%] SEC, 3 [1.6%] LA thrombus, 13 [6.9%] LAA thrombus), whereas the remaining patients formed group 2 (G2). The BMI, logarithmized (loge) leptin (G1: 2.0 ± 1.3 µg/ml, G2: 2.0 ± 1.1 µg/ml, p = 0.746) and visfatin serum levels (G1: 3.4 ± 0.3 ng/ml, G2: 3.4 ± 0.5 ng/ml, p = 0.900) did not significantly differ between the groups. Conversely, logarithmized adiponectin (G1: 3.3 ± 0.6 ng/ml, G2: 3.1 ± 0.7 ng/ml, p = 0.036) and resistin levels (G1: 1.8 ± 0.5 ng/ml, G2: 1.6 ± 0.5 ng/ml, p = 0.009) were higher in patients with the primary endpoint. Multivariate logistic regression analysis using a score that combined the individual adiponectin and resistin values in each patient corroborated this association. CONCLUSIONS: Our results suggest that adiponectin and resistin may act as potential biomarkers to identify individuals with AF who are at high thromboembolic risk.


Assuntos
Adipocinas/sangue , Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia/prevenção & controle , Trombose/prevenção & controle , Adiponectina/sangue , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Fibrilação Atrial/sangue , Fibrilação Atrial/diagnóstico por imagem , Biomarcadores/sangue , Índice de Massa Corporal , Estudos Transversais , Citocinas/sangue , Ecocardiografia Transesofagiana , Feminino , Alemanha , Humanos , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Nicotinamida Fosforribosiltransferase/sangue , Estudos Prospectivos , Resistina/sangue , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Tromboembolia/sangue , Tromboembolia/diagnóstico , Trombose/sangue , Trombose/diagnóstico por imagem , Fatores de Tempo , Resultado do Tratamento
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