Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 390
Filtrar
1.
PLoS One ; 15(12): e0243487, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33315883

RESUMO

Targeted proteomics utilizing antibody-based proximity extension assays provides sensitive and highly specific quantifications of plasma protein levels. Multivariate analysis of this data is hampered by frequent missing values (random or left censored), calling for imputation approaches. While appropriate missing-value imputation methods exist, benchmarks of their performance in targeted proteomics data are lacking. Here, we assessed the performance of two methods for imputation of values missing completely at random, the previously top-benchmarked 'missForest' and the recently published 'GSimp' method. Evaluation was accomplished by comparing imputed with remeasured relative concentrations of 91 inflammation related circulating proteins in 86 samples from a cohort of 645 patients with venous thromboembolism. The median Pearson correlation between imputed and remeasured protein expression values was 69.0% for missForest and 71.6% for GSimp (p = 5.8e-4). Imputation with missForest resulted in stronger reduction of variance compared to GSimp (median relative variance of 25.3% vs. 68.6%, p = 2.4e-16) and undesired larger bias in downstream analyses. Irrespective of the imputation method used, the 91 imputed proteins revealed large variations in imputation accuracy, driven by differences in signal to noise ratio and information overlap between proteins. In summary, GSimp outperformed missForest, while both methods show good overall imputation accuracy with large variations between proteins.


Assuntos
Proteômica/métodos , Adulto , Idoso , Algoritmos , Viés , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/normas , Feminino , Humanos , Interleucina-6/sangue , Interleucina-6/normas , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Proteômica/normas , Controle de Qualidade , Tromboembolia Venosa/metabolismo , Tromboembolia Venosa/patologia
2.
Blood ; 136(11): 1347-1350, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32746455

RESUMO

The association of severe coronavirus disease 2019 (COVID-19) with an increased risk of venous thromboembolism (VTE) has resulted in specific guidelines for its prevention and management. The VTE risk appears highest in those with critical care admission. The need for postdischarge thromboprophylaxis remains controversial, which is reflected in conflicting expert guideline recommendations. Our local protocol provides thromboprophylaxis to COVID-19 patients during admission only. We report postdischarge VTE data from an ongoing quality improvement program incorporating root-cause analysis of hospital-associated VTE (HA-VTE). Following 1877 hospital discharges associated with COVID-19, 9 episodes of HA-VTE were diagnosed within 42 days, giving a postdischarge rate of 4.8 per 1000 discharges. Over 2019, following 18 159 discharges associated with a medical admission; there were 56 episodes of HA-VTE within 42 days (3.1 per 1000 discharges). The odds ratio for postdischarge HA-VTE associated with COVID-19 compared with 2019 was 1.6 (95% confidence interval, 0.77-3.1). COVID-19 hospitalization does not appear to increase the risk of postdischarge HA-VTE compared with hospitalization with other acute medical illness. Given that the risk-benefit ratio of postdischarge thromboprophylaxis remains uncertain, randomized controlled trials to evaluate the role of continuing thromboprophylaxis in COVID-19 patients following hospital discharge are required.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Hospitalização/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Pneumonia Viral/complicações , Tromboembolia Venosa/etiologia , Infecções por Coronavirus/virologia , Seguimentos , Humanos , Pandemias , Pneumonia Viral/virologia , Prognóstico , Tromboembolia Venosa/patologia
3.
PLoS One ; 15(7): e0235639, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32649714

RESUMO

BACKGROUND: Treatment with vitamin K antagonists (VKA) requires a high proportion of time in the therapeutic range (TTR) and a low international normalised ratio (INR) variability to be maximally safe and effective. Switching from short-acting acenocoumarol to long-acting phenprocoumon could improve VKA control. AIMS: We assessed whether switching from acenocoumarol to phenprocoumon improves the time in the therapeutic range (TTR) and INR variability. METHODS AND RESULTS: In a retrospective cohort with data on 236,957 patients-years of VKA management from two first-line anticoagulation clinics in the Netherlands, we identified 124 patients in target range 2-3, 269 patients in target range 2-3.5 and 98 patients in target range 2.5-3.5 who switched from acenocoumarol to phenprocoumon. They were matched in a 1:2 ratio to non-switching controls using propensity score matching. Over the first 180 days after a switch, switchers' TTR declined 5 (95% CI 1 to 10), 10 (95% CI 7 to 13) and 5 (95% CI 0 to 11) percentage points relative to non-switchers, in target ranges 2-3, 2-3.5 and 2.5-3.5. Anticoagulation was more often supra-therapeutic in switchers, and switchers had a higher INR variability. In the following 180 days, TTR in switchers became 1 (95% CI -4 to 6), 4 (95% CI 0 to 7) and 6 (95% CI 1 to 12) percentage points better than in non-switchers. Switchers' INRs were much more stable than non-switchers'. CONCLUSION: Eventually, a switch from acenocoumarol to phenprocoumon leads to a higher TTR and a lower INR variability. However, this is preceded by a transition period with opposite effects. An improved conversion algorithm could possibly shorten the transition period. Until then, physicians and patients should decide whether switching is worth the increased risk during the transition phase.


Assuntos
Acenocumarol/uso terapêutico , Anticoagulantes/uso terapêutico , Coeficiente Internacional Normatizado/métodos , Femprocumona/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Risco , Resultado do Tratamento , Tromboembolia Venosa/patologia , Vitamina K/antagonistas & inibidores
4.
Hematol Oncol ; 38(4): 589-596, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32588912

RESUMO

The anticoagulant treatment for patients with hematologic malignancies is low molecular weight heparin (LMWH), which is considered the safest in this particular patients setting. Although direct oral anticoagulants (DOACs) have proven their efficacy and safety in patients with cancer, their use can be challenging in patients with hematologic malignancies due to the peculiarity of these neoplasms: high thrombotic risk, possible onset of thrombocytopenia and concomitant anticancer therapies. The aim of our study was to evaluate the efficacy and safety of DOACs for venous thromboembolism or atrial fibrillation in patients with hematologic malignancies and plasmatic DOACs level during anticancer therapy and at time of bleeding or thrombotic complications. We evaluated patients with hematologic malignancies treated with DOACs for venous thromboembolism or atrial fibrillation-therapy was maintained until the platelet count was ≥50 × 109 /L. In case of concomitant anticancer treatment and haemorrhagic or thrombotic events, we checked DOACs plasma levels (trough and peak). The patients evaluated were 135: 104/135 were on anticancer therapy. We did not observe either thrombotic or major haemorrhagic adverse events. Minor bleedings occurred in 10 patients and clinical relevant non-major (CRNM) in two patients. There was a statistically significant correlation between bleedings and myelodysplastic syndrome. DOACs resulted effective and safe in patients with hematologic malignancies. DOACs plasma level can be helpful in suggesting an early dose adjustment to prevent haemorrhagic adverse event in patients on concomitant anticancer therapy. Larger prospective studies including hematologic patients are warranted to confirm the safety and efficacy of DOACs.


Assuntos
Anticoagulantes/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Neoplasias Hematológicas/tratamento farmacológico , Hemorragia/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/induzido quimicamente , Fibrilação Atrial/patologia , Feminino , Seguimentos , Neoplasias Hematológicas/patologia , Hemorragia/induzido quimicamente , Hemorragia/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Tromboembolia Venosa/induzido quimicamente , Tromboembolia Venosa/patologia
5.
Zhonghua Zhong Liu Za Zhi ; 42(4): 340-345, 2020 Apr 23.
Artigo em Chinês | MEDLINE | ID: mdl-32375452

RESUMO

Objective: To verify the risk prediction efficacies of COMPASS-cancer associated thrombosis (COMPASS-CAT) risk assessment model and the new prediction probability model established based on COMPASS-CAT for venous thromboembolism (VTE) in hospitalized patients with non-small cell lung cancer (NSCLC). Methods: We retrospectively collected the clinical data of 373 patients with NSCLC admitted to National Clinical Research Center for Cancer/Cancer Hospital from March 2013 to June 2017. All of them were divided into VTE group (63 cases) and non-VTE group (310 cases) according to VTE occurred or not. According to the COMPASS-CAT risk assessment model, all patients were scored and classified by risk. Chi-square test was used to compare the clinical features between two groups, and multivariate logistic regression analysis was used to evaluate the independent risk factors of VTE in NSCLC patients. Based on the COMPASS-CAT risk assessment model, D-dimer≥1.03 mg/L and hemoglobin<10 g/dl were included to construct a new COMPASS-CAT prediction probability model, the ROC curve was also drawn. We used MedCalc software to compare the difference of ROC curves and analyze the application value of different risk assessment models in predicting VTE risk of NSCLC patients. Results: The incidence of VTE was 16.9% (63/373). The COMPASS-CAT score of VTE group was 6.37±3.40, which was higher than 2.74±2.04 of non-VTE group (P<0.001). Univariate analysis showed that the proportion of patients with KPS≤80, COMPASS-CAT≥7, D-dimer≥1.03 mg/L, central venous catheter (CVC), hemoglobin<10 g/L, cardiovascular complications≥2, hyperlipidemia, clinical stages Ⅲ and Ⅳ, KPS≤80 in VTE group was significantly higher than that in non-VTE group (P<0.05). Logistic regression analysis showed that D-dimer≥1.03 mg/L, compass-cat score≥7 and hemoglobin <10 g/dL were independent risk factors for VTE. Based on the COMPASS-CAT risk assessment model, a new risk assessment model of COMPASS-CAT was constructed by incorporating the variables of D-dimer ≥1.03 mg/L and hemoglobin <10 g/dl. The area under ROC curve (AUC) of COMPASS-CAT model and new COMPASS-CAT prediction probability model were 0.745 and 0.804, respectively. Compared with COMPASS-CAT model, AUC of new COMPASS-CAT prediction probability model increased by 0.059, with statistically significant difference(P=0.007). Conclusion: COMPASS-CAT risk assessment model can predict the risk of VTE in NSCLC patients, and the new COMPASS-CAT prediction probability model constructed by COMPASS-CAT model combined with D-dimer and hemoglobin variables can improve the accuracy of screening VTE risk factors in NSCLC patient.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/complicações , Neoplasias Pulmonares/complicações , Medição de Risco/métodos , Trombose , Tromboembolia Venosa/etiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/patologia
6.
Eur J Cancer ; 134: 75-85, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32473541

RESUMO

AIM OF STUDY: Venous thromboembolic events (VTEs) are significant complications in patients with systemic malignancies. Thrombosis risk is poorly defined for patients with brain metastasis, and available risk calculation scores are not validated for these patients. METHODS: We identified 811 patients with brain metastasis followed at our institution and reviewed electronic charts retrospectively for the occurrence of VTEs, along with candidate risk factors. Risk factors were tested in univariate and multivariate analyses and finally integrated in a score model for risk estimation. An independent cohort of 346 patients with brain metastasis was available for validation. RESULTS: VTEs were documented in 97 of 811 patients (12.0%). Primary tumours with high thrombogenicity (p = 0.02, hazard ratio 1.7, 95% confidence interval (CI) = 1.1-2.8), dexamethasone (p = 0.011, hazard ratio 2.27, 95% CI = 1.5-4.5), chemotherapy (p = 0.005, hazard ratio 3.4, 95% CI = 1.6-7.5), body mass index > 35 kg/m2 (p = 0.002, hazard ratio 3.4, 95% CI = 1.6-7.5) and immobilisation (p = 0.003, hazard ratio 2.4, 95% CI = 1.3-4.3) were confirmed to be independently associated with VTEs. We derived a score model for VTE risk estimation, the thrombogenic primary, immobilization, chemotherapy, obesity, steroid (PICOS) score (0-7 points). Receiver-operating characteristic curve analysis demonstrated its prognostic accuracy (area under the curve [AUC] = 0.71, 95% CI = 0.64-0.77), and its value for the evaluation of VTE risk was superior to that of other scores such as the Khorana (AUC = 0.51) or CONKO (AUC = 0.52) scores. The potential value of the PICOS score was confirmed in the validation cohort (AUC = 0.72, 95% CI = 0.63-0.82). CONCLUSIONS: The PICOS score may become a helpful tool for the identification of patients with brain metastasis at high risk for VTEs and for stratification in controlled studies.


Assuntos
Índice de Massa Corporal , Neoplasias Encefálicas/complicações , Neoplasias/complicações , Obesidade/fisiopatologia , Tromboembolia Venosa/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/secundário , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Tromboembolia Venosa/patologia , Adulto Jovem
7.
PLoS One ; 15(4): e0231411, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32271831

RESUMO

BACKGROUND: Venous thromboembolism (VTE) associated with surgery can cause serious comorbidities or death and imposes a substantial economic burden to society. The study examined VTE cases after surgery to determined how this condition imposed an economic burden on patients based on the national health insurance reimbursement database. Methods: This retrospective analysis adopted the public payer's perspective. The direct medical cost was estimated using data from the national claims database of Vietnam from Jan 1, 2017 to Sep 31, 2018. Adult patients who underwent surgeries were recruited for the study. Patients with a diagnostic code of up to 90 days after surgery were considered VTE cases with the outcome measure being the surgery-related costs within 90 days. RESULTS: The 90-day cost of VTE patients was found to be US$2,939. The rate of readmission increased by 5.4 times, the rate of outpatient visits increased by 1.8 times and total costs over 90 days in patients with VTE undergoing surgery increased by 2.2 times. Estimation using propensity score matching method showed that an increase of US$1,019 in the 90-day cost of VTE patients. CONCLUSION: The VTE-related costs can be used to assess the potential economic benefit and cost-savings from prevention efforts.


Assuntos
Efeitos Psicossociais da Doença , Tromboembolia Venosa/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Bases de Dados Factuais , Feminino , Humanos , Revisão da Utilização de Seguros , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Tromboembolia Venosa/economia , Tromboembolia Venosa/etiologia , Vietnã , Adulto Jovem
8.
Blood ; 135(3): 220-226, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31909784

RESUMO

Venous thromboembolism (VTE) incidence in children has sharply increased with the majority of cases secondary to central venous catheters (CVCs). Among CVCs, the number of peripherally inserted central catheters (PICCs) placed has risen significantly. In this multicenter, prospective, observational cohort study, we enrolled patients aged 6 months to 18 years with newly placed PICCs or tunneled lines (TLs). We evaluated the incidence of VTE, central line-associated bloodstream infections (CLABSIs), and catheter malfunctions in PICCs and TLs, and risk factors of CVC-related VTE. A total of 1967 CVCs were included in the analysis. The incidence of CVC-related VTE was 5.9% ± 0.63%. The majority of the cases, 80%, were in subjects with PICCs, which had a significantly higher risk of catheter-related VTE than subjects with TLs (hazard ratio [HR] = 8.5; 95% confidence interval [CI], 3.1-23; P < .001). PICCs were significantly more likely to have a CLABSI (HR = 1.6; 95% CI, 1.2-2.2; P = .002) and CVC malfunction (HR = 2.0; 95% CI, 1.6-2.4; P < .001). Increased risk of CVC-related VTE was found in patients with a prior history of VTE (HR = 23; 95% CI, 4-127; P < .001), multilumen CVC (HR = 3.9; 95% CI, 1.8-8.9; P = .003), and leukemia (HR = 3.5; 95% CI, 1.3-9.0; P = .031). Children with PICCs had a significantly higher incidence of catheter-related VTE, CLABSI, and CVC malfunction over TLs. The results suggest that pause be taken prior to placing CVCs, especially PICCs, due to the serious complications they have been shown to cause.


Assuntos
Infecções Relacionadas a Cateter/etiologia , Cateterismo Periférico/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Neoplasias/terapia , Tromboembolia Venosa/etiologia , Adolescente , Infecções Relacionadas a Cateter/patologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Neoplasias/patologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Tromboembolia Venosa/patologia
9.
Br J Haematol ; 188(6): 838-843, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31372991

RESUMO

Travel appears to be a weak risk factor for venous thromboembolism (VTE) and is more relevant for passengers with additional VTE risk factors. The association is not limited to air travel and is related to duration of travel. Life-threatening pulmonary embolism (PE) is rare. There is limited evidence to support interventions, including 'sensible measures', graduated compression stockings (GCS) and low-molecular-weight heparin (LMWH). It is difficult to confidently define a population who would benefit from thromboprophylaxis and no validated risk assessment exists for this purpose. LMWH has traditionally been used for flight thromboprophylaxis but a direct oral anticoagulant (DOAC) would be a more appealing oral option.


Assuntos
Curadoria de Dados/métodos , Viagem/tendências , Tromboembolia Venosa/etiologia , Trombose Venosa/etiologia , Humanos , Fatores de Risco , Tromboembolia Venosa/patologia , Trombose Venosa/patologia
10.
Cardiovasc Res ; 116(3): 698-707, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31135876

RESUMO

AIMS: The pathogenetic mechanisms underlying unprovoked venous thromboembolism (uVTE) are largely unknown. In this study, we investigated the molecular mechanisms involved in uVTE pathogenesis by using ex vivo expanded endothelial colony-forming cells (ECFCs), which represent a valuable non-invasive tool for the assessment of endothelial function. METHODS AND RESULTS: We isolated and expanded ECFCs from the peripheral blood of uVTE patients and observed that these cells underwent earlier senescence and showed lower growth rate compared with ECFCs obtained from healthy donors. Through microarray expression profiling, we demonstrated that 2905 genes were differentially expressed between patients and controls. Among them, the anti-angiogenic cytokine TNF superfamily member 15 (TNFSF15) and its death-receptor TNFRSF25 were up-regulated in uVTE ECFCs, and this finding was validated by RT-qPCR. TNFSF15 up-regulation was confirmed at the protein level in ECFC supernatants, and the in vivo relevance of these findings was further corroborated by demonstrating that also the plasmatic levels of TNFSF15 are increased in uVTE patients. After proving that exogenous TNFSF15 exerts pro-apoptotic and anti-proliferative activity on control ECFCs, we demonstrated through blocking experiments that TNFSF15 up-regulation contributes to impaired survival and proliferation of uVTE ECFCs. CONCLUSION: By providing evidence that TNFSF15 impairs ECFC functions crucial to endothelial repair, and that uVTE patients have increased TNFSF15 levels both ex vivo and in vivo, the results of this study suggest that pathologic up-regulation of TNFSF15-TNFRSF25 axis may contribute to uVTE pathogenesis, and may represent the target for novel therapeutic strategies aimed at preventing recurrences in uVTE patients.


Assuntos
Células Progenitoras Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Membro 25 de Receptores de Fatores de Necrose Tumoral/metabolismo , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Tromboembolia Venosa/metabolismo , Adulto , Apoptose , Estudos de Casos e Controles , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Senescência Celular , Células Progenitoras Endoteliais/patologia , Endotélio Vascular/patologia , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Membro 25 de Receptores de Fatores de Necrose Tumoral/genética , Transdução de Sinais , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Tromboembolia Venosa/patologia , Tromboembolia Venosa/fisiopatologia
11.
J Clin Oncol ; 38(5): 496-520, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-31381464

RESUMO

PURPOSE: To provide updated recommendations about prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer. METHODS: PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and meta-analyses of RCTs published from August 1, 2014, through December 4, 2018. ASCO convened an Expert Panel to review the evidence and revise previous recommendations as needed. RESULTS: The systematic review included 35 publications on VTE prophylaxis and treatment and 18 publications on VTE risk assessment. Two RCTs of direct oral anticoagulants (DOACs) for the treatment of VTE in patients with cancer reported that edoxaban and rivaroxaban are effective but are linked with a higher risk of bleeding compared with low-molecular-weight heparin (LMWH) in patients with GI and potentially genitourinary cancers. Two additional RCTs reported on DOACs for thromboprophylaxis in ambulatory patients with cancer at increased risk of VTE. RECOMMENDATIONS: Changes to previous recommendations: Clinicians may offer thromboprophylaxis with apixaban, rivaroxaban, or LMWH to selected high-risk outpatients with cancer; rivaroxaban and edoxaban have been added as options for VTE treatment; patients with brain metastases are now addressed in the VTE treatment section; and the recommendation regarding long-term postoperative LMWH has been expanded. Re-affirmed recommendations: Most hospitalized patients with cancer and an acute medical condition require thromboprophylaxis throughout hospitalization. Thromboprophylaxis is not routinely recommended for all outpatients with cancer. Patients undergoing major cancer surgery should receive prophylaxis starting before surgery and continuing for at least 7 to 10 days. Patients with cancer should be periodically assessed for VTE risk, and oncology professionals should provide patient education about the signs and symptoms of VTE.Additional information is available at www.asco.org/supportive-care-guidelines.


Assuntos
Neoplasias/complicações , Tromboembolia Venosa/terapia , Anticoagulantes/administração & dosagem , Humanos , Metanálise como Assunto , Neoplasias/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/patologia , Tromboembolia Venosa/prevenção & controle
12.
J Clin Lab Anal ; 34(1): e23010, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31508844

RESUMO

BACKGROUND: Acute venous thromboembolism (VTE) refers to deep venous thrombosis (DVT) of the extremities or pulmonary embolism (PE), or to both. Reliable imaging is not always available making a serologic diagnosis, or biomarker, highly desirable. OBJECTIVE: This study aimed to examine the role of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and mean platelet volume (MPV) in detection patients with acute VTE. METHODS: A total of 327 patients with initial diagnosis of acute VTE who were admitted to Ziv hospital were evaluated. Of them, 272 patients with definitive diagnosis of VTE, and 55 patients without VTE were used as control group. Complete blood count (CBC), measurements of NLR, MPV, and PLR were determined at admission. RESULTS: Patients with VTE were older than controls (62 ± 18.9 vs 55.4 ± 15.1 years, respectively, P = .03). Female gender was predominant in the two groups. In the study group, 178/272 (66%) had DVT, 84/272 (31%) had pulmonary embolism (PE), and the rest had DVT and PE. NLR, MPV, and PLR were found to be significantly elevated in acute VTE compared to control (P < .001, P = .008, P = .014, respectively). A ROC curve analysis of NLR and MPV for predicting acute VTE was performed which found a cut-off value of 5.3 for NLR, an area under curve of (0.67 (0.60-0.75), P < .001, with a sensitivity of 69% and specificity of 57%. and a cut-off value of 8.6 for MPV, an area under curve of (0.61 [0.53-0.68], P = .014, with a sensitivity of 52% and specificity of 67%. Multivariate logistic regression model found that NLR (OR 1.2, 95% CI [1.01-1.4], P = .041) and MPV (OR 1.5, 95%CI [1.07-2.12], P = .5) were associated with acute VTE. CONCLUSIONS: Neutrophil-lymphocyte ratio and MPV could be beneficial predictors for the early detection of potential acute VTE.


Assuntos
Linfócitos/patologia , Volume Plaquetário Médio , Neutrófilos/patologia , Tromboembolia Venosa/sangue , Tromboembolia Venosa/patologia , Doença Aguda , Biomarcadores/sangue , Feminino , Humanos , Inflamação/sangue , Contagem de Leucócitos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Curva ROC
14.
J Cancer Res Clin Oncol ; 146(2): 467-475, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31734835

RESUMO

PURPOSE: The expression of active tissue factor (TF) on the surface of microvesicles (MVs) is essential for the activation of the coagulation system and transduction of the signaling pathways in cancer cells. In its use as a biomarker for cancer-associated venous thromboembolism (VTE), TF has shown high expression variability. As a contribution to this discussion, we present a study investigating plasma samples from patients with various progressive tumors at high risk for VTE. METHODS: Based on our previous study uncovering microvesicles (MVs), the larger ectosome-like extracellular vesicles (EV), as the major source of TF activity in EV preparations, we now determined TF activity on enriched MVs isolated from plasma of cancer patients and compared it with that on MVs from healthy individuals. RESULTS: We found considerably higher amounts of MVs as well as higher levels of MV-bound TF activities in the plasma of cancer patients. We also show that preparations from plasma of cancer patients have the potency to induce ERK phosphorylation in a human tumor cell line through proteinase-activated receptor two (PAR2) activation. CONCLUSION: We suggest that MVs instead of whole EV preparations, and TF activity rather than its antigenic quantification should be used in clinical studies for identifying patients with progressive tumors at high risk for VTE.


Assuntos
Tromboplastina/metabolismo , Idoso , Estudos de Casos e Controles , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patologia , Feminino , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Fosforilação , Tromboplastina/biossíntese , Tromboembolia Venosa/sangue , Tromboembolia Venosa/patologia
15.
Support Care Cancer ; 28(8): 3755-3761, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31828489

RESUMO

INTRODUCTION: Cancer-associated venous thromboembolism (CAT) is a major complication of malignancy. Our goal was to develop a prediction model for VTE that better represented to the population seen at large referral cancer centers. MATERIALS AND METHODS: This study was nested in a prospective cohort study at the University of Texas MD Anderson Cancer Center that evaluated adult patients during outpatient cancer-staging computed tomography to estimate the prevalence of incidental VTE. Data from patients in whom incidental VTE was not found on initial CT were collected until 24 months ± 7 days from the study inclusion date to determine the occurrence of new VTE events. Demographics, clinical data, current cancer treatment information, and the use of erythropoietin stimulating agents (ESAs) along with hematologic variables were collected in all patients and analyzed to determine differences between those who developed VTE versus those who did not. All candidate variables with significance p value (≤ 0.1) under univariate analysis were considered to enter the final multivariate model. RESULTS: Data of 548 patients were analyzed. The presence of metastatic disease and the use of platinum-based chemotherapy were strongly associated with CAT occurrence. The use of ESAs and specific malignancies showed trends of association with CAT, while associations were not statistically significant.Those characteristics were utilized to develop a clinical prediction model for CAT readily available and effective (c-index = 0.74). CONCLUSION: Our model is effective and easy to incorporate in busy clinical settings and it does not depend on esoteric or difficult-to-obtain laboratory testing. Future external validation studies may provide further evidence for the applicability of our results.


Assuntos
Neoplasias/complicações , Tromboembolia Venosa/epidemiologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Prevalência , Estudos Prospectivos , Fatores de Risco , Estados Unidos , Tromboembolia Venosa/patologia
16.
Dis Markers ; 2019: 4923535, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827635

RESUMO

The use of hormonal contraception is associated with an increased risk of venous thromboembolism (VTE). Unfavorably altered fibrin clot phenotype has been reported in patients following unprovoked VTE who are at risk of recurrences. It remains unknown whether fibrin clot characteristics in women with contraception-related VTE differ from those in unprovoked VTE. We studied three age-matched groups of women: (1) after contraception-related VTE, (n = 48) (2) after unprovoked VTE (n = 48), and (3) controls (n = 48). Plasma fibrin clot permeability (K s), turbidity of clot formation, efficiency of fibrinolysis using clot lysis time (CLT), and rate of increase in D-dimer during lytic clot degradation (D-Drate), along with thrombin generation and fibrinolysis proteins were determined. Compared with the controls, patients following contraception-related and unprovoked VTE formed faster (lag phase, -8.8% and -20.4%, respectively) fibrin clots of increased density (K s , -8.6% and -13.4%, respectively) displaying impaired fibrinolysis as evidenced by prolonged CLT (+11.5% and +14.5%, respectively) and lower D-Drate (-7.1% and -5.6%, respectively), accompanied with higher plasminogen activator inhibitor-1 (PAI-1, +14.9% and +17.8%, respectively) and elevated peak thrombin generation (+63.8% and +36.7%, respectively). The only differences between women with unprovoked and contraception-related VTE were lower fibrin mass in plasma clots (D-Dmax, -8.6%), along with higher peak thrombin generation (+19.8%) and shorter lag phase (-6.8%) in the latter group. This study suggests that women after contraception-related VTE, similar to those following unprovoked VTE, have denser fibrin clot formation and impaired clot lysis. These findings might imply higher risk of VTE recurrence in women with the prothrombotic clot phenotype.


Assuntos
Tempo de Lise do Coágulo de Fibrina/estatística & dados numéricos , Fibrina/metabolismo , Contracepção Hormonal/efeitos adversos , Tromboembolia Venosa/patologia , Adulto , Estudos de Casos e Controles , Feminino , Fibrinólise , Seguimentos , Humanos , Fenótipo , Recidiva , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/metabolismo
17.
Hematology Am Soc Hematol Educ Program ; 2019(1): 359-366, 2019 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-31808864

RESUMO

Pregnancy in women with sickle cell disease (SCD) is associated with increased maternal and fetal morbidity and mortality. Outcomes vary widely owing to methodological limitations of clinical studies, but overall, hypertensive disorders of pregnancy, venothromboembolism, poor fetal growth, and maternal and perinatal mortality are increased globally. Few therapeutic interventions have been explored other than prophylactic and selective transfusion therapy. Unfortunately, existing data are limited, and it remains unclear whether prophylactic use of chronic transfusions will improve pregnancy outcomes. Management of pregnant women with SCD is best accomplished with a multidisciplinary team that includes a sickle cell expert and an obstetrician familiar with high-risk pregnancies. Women with SCD should have individualized care plans that outline management of acute pain and guidelines for transfusion therapy. Neonates require close monitoring for neonatal abstinence syndrome and hemolytic disease of the newborn. Ideally all young women with SCD will have a "reproductive life plan" developed as a component of preconception counseling and health promotion. Research leading to improved pregnancy management focused on diminishing adverse maternal and neonatal outcomes is overdue. International collaborations should be considered to improve subject recruitment and foster timely completion of clinical trials. Additional therapeutic interventions outside of transfusion therapy should be explored.


Assuntos
Anemia Falciforme , Transfusão de Sangue , Eritroblastose Fetal , Retardo do Crescimento Fetal , Síndrome de Abstinência Neonatal , Complicações Hematológicas na Gravidez , Tromboembolia Venosa , Adulto , Anemia Falciforme/metabolismo , Anemia Falciforme/patologia , Anemia Falciforme/terapia , Eritroblastose Fetal/metabolismo , Eritroblastose Fetal/patologia , Eritroblastose Fetal/prevenção & controle , Feminino , Retardo do Crescimento Fetal/metabolismo , Retardo do Crescimento Fetal/terapia , Humanos , Síndrome de Abstinência Neonatal/metabolismo , Síndrome de Abstinência Neonatal/patologia , Síndrome de Abstinência Neonatal/prevenção & controle , Gravidez , Complicações Hematológicas na Gravidez/metabolismo , Complicações Hematológicas na Gravidez/patologia , Complicações Hematológicas na Gravidez/terapia , Tromboembolia Venosa/metabolismo , Tromboembolia Venosa/patologia , Tromboembolia Venosa/terapia
18.
Blood ; 134(26): 2399-2413, 2019 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-31877217

RESUMO

Patients with malignancy are at 4- to 7-fold higher risk of venous thromboembolism (VTE), a potentially fatal, yet preventable complication. Although general mechanisms of thrombosis are enhanced in these patients, malignancy-specific triggers and their therapeutic implication remain poorly understood. Here we examined a colon cancer-specific VTE model and probed a set of metabolites with prothrombotic propensity in the inferior vena cava (IVC) ligation model. Athymic mice injected with human colon adenocarcinoma cells exhibited significantly higher IVC clot weights, a biological readout of venous thrombogenicity, compared with the control mice. Targeted metabolomics analysis of plasma of mice revealed an increase in the blood levels of kynurenine and indoxyl sulfate (tryptophan metabolites) in xenograft-bearing mice, which correlated positively with the increase in the IVC clot size. These metabolites are ligands of aryl hydrocarbon receptor (AHR) signaling. Accordingly, plasma from the xenograft-bearing mice activated the AHR pathway and augmented tissue factor (TF) and plasminogen activator inhibitor 1 (PAI-1) levels in venous endothelial cells in an AHR-dependent manner. Consistent with these findings, the endothelium from the IVC of xenograft-bearing animals revealed nuclear AHR and upregulated TF and PAI-1 expression, telltale signs of an activated AHR-TF/PAI-1 axis. Importantly, pharmacological inhibition of AHR activity suppressed TF and PAI-1 expression in endothelial cells of the IVC and reduced clot weights in both kynurenine-injected and xenograft-bearing mice. Together, these data show dysregulated tryptophan metabolites in a mouse cancer model, and they reveal a novel link between these metabolites and the control of the AHR-TF/PAI-1 axis and VTE in cancer.


Assuntos
Neoplasias do Colo/complicações , Modelos Animais de Doenças , Metaboloma , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Tromboplastina/metabolismo , Tromboembolia Venosa/etiologia , Animais , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Nus , Transdução de Sinais , Triptofano/metabolismo , Tromboembolia Venosa/metabolismo , Tromboembolia Venosa/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Zhongguo Fei Ai Za Zhi ; 22(12): 747-751, 2019 Dec 20.
Artigo em Chinês | MEDLINE | ID: mdl-31874668

RESUMO

Venous thromboembolism (VTE) is a common perioperative complication in patients with thoracic malignant tumor. Once it occurs, it will not only affect the prognosis of patients, but also occupy a lot of medical resources, which is gradually causing our widespread attention. However, the understanding of VTE in thoracic surgery in our country is relatively late, and the recognition and attention are not enough, and there is still a lack of guidance support for perioperative VTE. Based on the current understanding and preventive measures of VTE in thoracic surgery in China, The China National Research Collaborative Group released the first edition of Chinese experts consensus on the perioperative VTE prophylaxis in 2018. This article will interpret the high-risk patients with perioperative VTE in patients with thoracic malignant tumors, in order to provide a better understanding of Chinese experts consensus for readers.


Assuntos
Neoplasias Torácicas/cirurgia , Tromboembolia Venosa/patologia , Tromboembolia Venosa/cirurgia , Adulto , China , Feminino , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Procedimentos Cirúrgicos Torácicos
20.
Nat Genet ; 51(11): 1574-1579, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31676865

RESUMO

Venous thromboembolism is a significant cause of mortality1, yet its genetic determinants are incompletely defined. We performed a discovery genome-wide association study in the Million Veteran Program and UK Biobank, with testing of approximately 13 million DNA sequence variants for association with venous thromboembolism (26,066 cases and 624,053 controls) and meta-analyzed both studies, followed by independent replication with up to 17,672 venous thromboembolism cases and 167,295 controls. We identified 22 previously unknown loci, bringing the total number of venous thromboembolism-associated loci to 33, and subsequently fine-mapped these associations. We developed a genome-wide polygenic risk score for venous thromboembolism that identifies 5% of the population at an equivalent incident venous thromboembolism risk to carriers of the established factor V Leiden p.R506Q and prothrombin G20210A mutations. Our data provide mechanistic insights into the genetic epidemiology of venous thromboembolism and suggest a greater overlap among venous and arterial cardiovascular disease than previously thought.


Assuntos
Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Doenças Vasculares/genética , Tromboembolia Venosa/genética , Idoso , Animais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/genética , Fatores de Risco , Reino Unido/epidemiologia , Doenças Vasculares/epidemiologia , Doenças Vasculares/patologia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA