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1.
Clin Appl Thromb Hemost ; 28: 10760296221084307, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35249379

RESUMO

Measuring direct oral anticoagulant (DOAC) concentrations might be necessary in certain clinical situations but is not routinely performed. The DOAC Dipstick is a new rapid test for detecting DOACs in urine. The aim of this study was to evaluate the possible uses and limitations of the DOAC Dipstick and to compare visual analysis and DOASENSE Reader analysis of DOAC Dipstick pads. Plasma and urine samples were collected from 23 patients taking DOACs. DOAC concentrations in plasma and urine were measured by chromogenic substrate assays and in urine also by the DOAC Dipstick. Plasma concentrations were dichotomized at a threshold of ≥30 ng/mL. Patient samples were compared with samples from control individuals not using anticoagulants (n = 10) and with DOASENSE control urines. The Combur-10 test was used to measure parameters that may affect urine color and hence the interpretation of the DOAC Dipstick result. DOAC Dipstick test results were positive in 21/23 patient urine samples at a plasma DOAC concentration of ≥30 ng/mL and in 2/23 patient urine samples at a plasma DOAC concentration of <30 ng/mL. Inter-observer agreement was above 90% for visual analysis of patient urine samples and was 100% for DOASENSE Reader analysis of patient urines and for analysis of control group urines and DOASENSE control urines. Abnormalities in urine color detected by the Combur-10 test did not affect the DOAC Dipstick results. DOAC Dipstick detects DOACs in urine at a plasma threshold of ≥30 ng/mL. Positive DOAC Dipstick results should be confirmed by measuring DOAC plasma concentration.


Assuntos
Anticoagulantes/farmacocinética , Coagulação Sanguínea/efeitos dos fármacos , Tromboembolia Venosa/prevenção & controle , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Biomarcadores/sangue , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Curva ROC , Urinálise/métodos , Tromboembolia Venosa/sangue , Tromboembolia Venosa/urina
2.
Anesth Analg ; 134(3): 606-614, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35180177

RESUMO

BACKGROUND: Bleeding can be a significant problem after cardiac surgery. As a result, venous thromboembolism (VTE) or anticoagulation or both following mechanical valve implantation are often delayed in these patients. The calibrated automated thrombin (CAT) generation assay has become the gold standard to evaluate thrombin generation, a critical step in clot formation independent of other hemostatic processes (eg, platelet activation, fibrin cross-linking, and fibrinolysis), and is increasingly used to examine thrombotic and hemorrhagic outcomes. No study has currently used this assay to compare the thrombin generation profiles of cardiac surgical patients to noncardiac surgical patients. We hypothesize that noncardiac patients may be less prone to postoperative changes in thrombin generation. METHODS: A prospective, observational, cohort study was undertaken using blood samples from 50 cardiac and 50 noncardiac surgical patients preoperatively, immediately postoperatively, and on postoperative days 1 to 4. Platelet-poor plasma samples were obtained from patients preoperatively, on arrival to the postanesthesia care unit (PACU) or intensive care unit (ICU), and daily on postoperative days 1 to 4 if patients remained inpatient. Samples were evaluated for CAT measurements. Patient and surgical procedure characteristics were obtained from the electronic medical record. RESULTS: The primary outcome variable, median endogenous thrombin potential (ETP), measured in nanomolar × minutes (nM × min), was decreased 100% in cardiac surgical versus 2% in noncardiac patients (P < .001). All parameters of thrombin generation were similarly depressed. Cardiac (versus noncardiac) surgical type was associated with -76.5% difference of percent change in ETP on multivariable regression analysis (95% confidence interval [CI], -87.4 to -65.5; P value <.001). CONCLUSIONS: Cardiac surgical patients exhibit a profound decrease in thrombin generation postoperatively compared with noncardiac surgical patients evaluated by this study. Hemodilution and coagulation factor depletion likely contribute to this decreased thrombin generation after cardiac surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Procedimentos Cirúrgicos Operatórios , Trombina/biossíntese , Idoso , Período de Recuperação da Anestesia , Fatores de Coagulação Sanguínea , Estudos de Coortes , Feminino , Hemodiluição , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Trombina/análise , Tromboembolia Venosa/sangue
3.
J Vasc Surg Venous Lymphat Disord ; 10(1): 8-13, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34171532

RESUMO

OBJECTIVE: Plasma D-dimer levels >5000 ng/mL are encountered in a number of conditions other than venous thromboembolism (VTE). Recent studies have used plasma D-dimer levels as a prognostic indicator for coronavirus disease 2019 (COVID-19) infection. The implications of abnormal levels are less clear for patients diagnosed with COVID-19 with a baseline elevation in plasma D-dimer levels. In the present study, we reviewed the occurrence of plasma D-dimer levels >5000 ng/mL and investigated the clinical significance of this finding before the onset of the COVID-19 pandemic. METHODS: Inpatient records for a 4-year period were screened for laboratory results of plasma D-dimer levels >5000 ng/mL. The patient data were reviewed for the clinical identifiers commonly associated with elevated plasma D-dimer levels, including VTE, cancer, sepsis, pneumonia, other infection, bleeding, and trauma. The patients were then categorized into groups stratified by the plasma D-dimer level to allow for comparisons between the various clinical diagnoses. RESULTS: A total of 671 patients were included in the present study. VTE was the most common diagnosis for patients with a plasma D-dimer level >5000 ng/mL, followed by cancer and pneumonia. Multiple clinical diagnoses were present in 61% of the patients. No clear cause for the ultra-high plasma D-dimer level could be identified in 11.3% of the patients. Among the patients lacking a clinical diagnosis at discharge, mortality was 24% in the 5000- to 10,000-ng/mL group, 28.6% in the 10,000- to 15,000-ng/mL group, and 75% in the >15,000-ng/mL group. CONCLUSIONS: VTE, cancer, and pneumonia were frequently present when ultra-high plasma D-dimer levels were encountered, and mortality was high when the levels were >15,000 ng/mL. The results from our study from a pre-COVID-19 patient population suggest that ultra-high plasma D-dimer levels indicate the presence of severe underlying disease. This should be considered when using the plasma D-dimer level as a screening tool or prognostic indicator for COVID-19 infection.


Assuntos
COVID-19/complicações , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Tromboembolia Venosa/sangue , Idoso , Biomarcadores/sangue , COVID-19/sangue , COVID-19/epidemiologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Ohio/epidemiologia , Pandemias , Estudos Retrospectivos , Fatores de Tempo , Tromboembolia Venosa/etiologia
5.
Thromb Haemost ; 122(3): 386-393, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33984866

RESUMO

BACKGROUND: Warfarin remains widely used and a key comparator in studies of other direct oral anticoagulants. As longer-than-needed warfarin prescriptions are often provided to allow for dosing adjustments according to international normalized ratios (INRs), the common practice of using a short allowable gap between dispensings to define warfarin discontinuation may lead to substantial misclassification of warfarin exposure. We aimed to quantify such misclassification and determine the optimal algorithm to define warfarin discontinuation. METHODS: We linked Medicare claims data from 2007 to 2014 with a multicenter electronic health records system. The study cohort comprised patients ≥65 years with atrial fibrillation and venous thromboembolism initiating warfarin. We compared results when defining warfarin discontinuation by (1) different gaps (3, 7, 14, 30, and 60 days) between dispensings and (2) having a gap ≤60 days or bridging larger gaps if there was INR ordering at least every 42 days (60_INR). Discontinuation was considered misclassified if there was an INR ≥2 within 7 days after the discontinuation date. RESULTS: Among 3,229 patients, a shorter gap resulted in a shorter mean follow-up time (82, 95, 117, 159, 196, and 259 days for gaps of 3, 7, 14, 30, 60, and 60_INR, respectively; p < 0.001). Incorporating INR (60_INR) can reduce misclassification of warfarin discontinuation from 68 to 4% (p < 0.001). The on-treatment risk estimation of clinical endpoints varied significantly by discontinuation definitions. CONCLUSION: Using a short gap between warfarin dispensings to define discontinuation may lead to substantial misclassification, which can be improved by incorporating intervening INR codes.


Assuntos
Fibrilação Atrial , Tromboembolia Venosa , Varfarina/uso terapêutico , Suspensão de Tratamento/estatística & dados numéricos , Idoso , Anticoagulantes/uso terapêutico , Fibrilação Atrial/sangue , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Codificação Clínica/métodos , Codificação Clínica/organização & administração , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Humanos , Coeficiente Internacional Normatizado/métodos , Masculino , Medicare/estatística & dados numéricos , Padrões de Prática Médica , Estados Unidos , Tromboembolia Venosa/sangue , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamento farmacológico
6.
J Atheroscler Thromb ; 29(1): 82-98, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33298665

RESUMO

AIM: Feedback activation of factor XI (FXI) by thrombin is believed to play a critical role in the amplification phase of thrombin generation and to contribute to thrombosis development and hemostasis. However, the activation of FXI by thrombin has been shown in vitro to require a cofactor. In this study, the role of thrombin in activated FXI (FXIa) formation in vivo is investigated. METHODS: The study population comprised probands in whom coagulation activation was triggered by low-dose (15 µg/kg) recombinant activated factor VII (rFVIIa, n=89), of whom 34 with (VTE+) and 45 without a history of venous thromboembolism (VTE-), and patients undergoing major orthopedic surgeries (n=45). FXIa was quantified via an enzyme capture assay using a monoclonal FXI-specific antibody. Thrombin formation was monitored using an oligonucleotide-based enzyme capture assay and the thrombin activation markers prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT). RESULTS: In the rFVIIa cohort, FXIa and thrombin remained below their lower limit of quantification of 3.48 and 1.06 pmol/L, respectively. By contrast, during the surgeries, median FXIa levels increased from 3.69 pmol/L pre-operatively to 9.41 pmol/L mid-operatively (P=4·10-4) and remained significantly elevated 24 h thereafter, with 9.38 pmol/L (P=0.001). Peak levels of F1+2 were comparable in the VTE+, VTE-, and surgery cohort (235, 268, and 253 pmol/L), whereas peak TAT levels were higher in the surgery cohort (53.1, 33.9, and 147.6 pmol/L). CONCLUSIONS: Under in vivo conditions, the activation of FXI requires specific local features that are present at the wounded site including potential cofactors of thrombin.


Assuntos
Fator VIIa/uso terapêutico , Fator XIa/metabolismo , Ferida Cirúrgica/sangue , Trombina/metabolismo , Tromboembolia Venosa/sangue , Adulto , Idoso , Antitrombina III , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Ortopédicos/efeitos adversos , Fragmentos de Peptídeos/sangue , Peptídeo Hidrolases/sangue , Protrombina , Proteínas Recombinantes/uso terapêutico , Ferida Cirúrgica/etiologia , Adulto Jovem
7.
World Neurosurg ; 157: e357-e363, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34655821

RESUMO

BACKGROUND: Prior studies demonstrated reduced risk for venous thromboembolism (VTE) in neurosurgical patients secondary to prophylaxis with both heparin and low-molecular-weight heparin. The ability to monitor low-molecular-weight heparin by obtaining anti-factor Xa (anti-Xa) serum levels provides an opportunity to evaluate safety and efficacy. The aim of this study was to describe characteristics of patients who have anti-Xa levels outside of the goal range (0.2-0.4/0.5 IU/mL) and investigate incidence of major bleeding and VTE. METHODS: A single-center, retrospective, observational study was conducted on neurosurgical patients receiving enoxaparin for VTE prophylaxis between August 2019 and December 2020. Significance testing was conducted via Fisher exact test and independent samples t test. RESULTS: The study included 85 patients. Patients were less likely to have an anti-Xa level in the goal range if they were male, had a higher weight, or were morbidly obese. Three neuroendovascular patients (3.5%) experienced a major bleed. Serum anti-Xa levels were significantly higher in patients who experienced major bleeds compared with patients who did not (0.45 ± 0.16 IU/mL vs. 0.28 ± 0.09 IU/mL, P = 0.003). Patients with a supraprophylactic anti-Xa level (>0.5 IU/mL) were more likely to experience a major bleed (P = 0.005). One VTE event occurred: the patient experienced a pulmonary embolism with anti-Xa level at goal. CONCLUSIONS: Anti-Xa-guided enoxaparin dosing for VTE prophylaxis in neurosurgical patients may help prevent major bleeding. These data suggest that a higher anti-Xa level may predispose patients to major bleeding. Further evaluation is needed to identify the goal anti-Xa level for VTE prophylaxis in this population.


Assuntos
Enoxaparina/sangue , Inibidores do Fator Xa/sangue , Hemorragia/sangue , Procedimentos Neurocirúrgicos/tendências , Profilaxia Pré-Exposição/tendências , Adulto , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/sangue , Monitoramento de Medicamentos/métodos , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/sangue , Obesidade Mórbida/cirurgia , Profilaxia Pré-Exposição/métodos , Estudos Retrospectivos , Fatores Sexuais , Tromboembolia Venosa/sangue , Tromboembolia Venosa/prevenção & controle
8.
J Trauma Acute Care Surg ; 92(1): 93-97, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34561398

RESUMO

BACKGROUND: Trauma is a major risk factor for the development of a venous thromboembolism (VTE). After observing higher than expected VTE rates within our center's Trauma Quality Improvement Program data, we instituted a change in our VTE prophylaxis protocol, moving to enoxaparin dosing titrated by anti-Xa levels. We hypothesized that this intervention would lower our symptomatic VTE rates. METHODS: Adult trauma patients at a single institution meeting National Trauma Data Standard criteria from April 2015 to September 2019 were examined with regards to VTE chemoprophylaxis regimen and VTE incidence. Two groups of patients were identified based on VTE protocol-those who received enoxaparin 30 mg twice daily without routine anti-Xa levels ("pre") versus those who received enoxaparin 40 mg twice daily with dose titrated by serial anti-Xa levels ("post"). Univariate and multivariate analyses were performed to define statistically significant differences in VTE incidence between the two cohorts. RESULTS: There were 1698 patients within the "pre" group and 1406 patients within the "post" group. The two groups were essentially the same in terms of demographics and risk factors for bleeding or thrombosis. There was a statistically significant reduction in VTE rate (p = 0.01) and deep vein thrombosis rate (p = 0.01) but no significant reduction in pulmonary embolism rate (p = 0.21) after implementation of the anti-Xa titration protocol. Risk-adjusted Trauma Quality Improvement Program data showed an improvement in rate of symptomatic pulmonary embolism from fifth decile to first decile. CONCLUSION: A protocol titrating prophylactic enoxaparin dose based on anti-Xa levels reduced VTE rates. Implementation of this type of protocol requires diligence from the physician and pharmacist team. Further research will investigate the impact of protocol compliance and time to appropriate anti-Xa level on incidence of VTE. LEVEL OF EVIDENCE: Therapeutic/care management, Level IV.


Assuntos
Cálculos da Dosagem de Medicamento , Enoxaparina , Inibidores do Fator Xa , Hemorragia , Tromboembolia Venosa , Ferimentos e Lesões , Testes de Coagulação Sanguínea/métodos , Quimioprevenção/efeitos adversos , Quimioprevenção/métodos , Quimioprevenção/normas , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Fator Xa/análise , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/sangue , Feminino , Hemorragia/sangue , Hemorragia/etiologia , Hemorragia/prevenção & controle , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Embolia Pulmonar/sangue , Embolia Pulmonar/etiologia , Embolia Pulmonar/prevenção & controle , Melhoria de Qualidade/organização & administração , Sistema de Registros/estatística & dados numéricos , Risco Ajustado/métodos , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Ferimentos e Lesões/complicações , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/terapia
9.
Int J Lab Hematol ; 44(1): 163-167, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34523813

RESUMO

INTRODUCTION: Direct oral anticoagulant (DOAC)-inhibiting factor Xa (FXa-DOAC) are being increasingly used as prophylaxis of venous thromboembolism and for prevention of stroke in patients with atrial fibrillation. In contrast to vitamin K antagonists, DOACs do not require monitoring in general. However, it is sometimes of value in the acute setting, for instance when considering a reversal agent in uncontrolled bleeding in patients on DOAC. METHODS: We evaluated if a low-molecular weight heparin (LMWH)-calibrated anti-factor Xa assay could be used to estimate FXa-DOAC concentration in the concentration range <100 ng/mL by spiking known concentrations of FXa-DOAC and from those result calculate the FXa-DOAC concentration from the response of the LMWH assay. This procedure was then evaluated by comparing the result with a drug-calibrated chromogenic assay and liquid chromatography tandem mass spectrometry (LC-MS/MS) on clinical plasma samples from patients treated with apixaban or rivaroxaban. RESULTS: Although the measuring range was narrower for the LMWH-calibrated assay, concentrations recalculated from the LMWH assay was comparable with those measured by the drug-calibrated method when compared with LC-MS/MS. CONCLUSION: We suggest that an LMWH-calibrated anti-factor Xa assay can be used after characterization of the response of FXa-DOACs to give guidance on the concentration of apixaban and rivaroxaban. Shorter turnaround time than LC-MS/MS and the greater availability than drug-calibrated chromogenic assays could make this a valuable option in the acute setting.


Assuntos
Testes de Coagulação Sanguínea/métodos , Inibidores do Fator Xa/farmacocinética , Pirazóis/farmacocinética , Piridonas/farmacocinética , Rivaroxabana/farmacocinética , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia Venosa/sangue , Tromboembolia Venosa/prevenção & controle , Fibrilação Atrial/sangue , Fibrilação Atrial/complicações , Testes de Coagulação Sanguínea/normas , Cromatografia Líquida , Tomada de Decisão Clínica , Gerenciamento Clínico , Suscetibilidade a Doenças , Monitoramento de Medicamentos/métodos , Inibidores do Fator Xa/administração & dosagem , Heparina de Baixo Peso Molecular , Humanos , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Reprodutibilidade dos Testes , Rivaroxabana/administração & dosagem , Sensibilidade e Especificidade , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Espectrometria de Massas em Tandem , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologia
10.
J Vasc Surg Venous Lymphat Disord ; 10(2): 463-468.e2, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34487891

RESUMO

OBJECTIVE: We compared the in vitro clot-capturing efficiencies (CCEs) of commercially available retrievable inferior vena cava (IVC) filters. METHODS: Four types of commercially available retrievable IVC filters were included in the present study: Denali (BD, Franklin Lakes, NJ), OptEase (Cordis Corp, Hialeah, Fla), Celect (Cook Medical, Bloomington, Ind), and Option (Argon Medical Devices, Frisco, Tex). The CCE of each IVC filter for 10 different size clots, ranging from 2 mm × 10 mm to 6 mm × 20 mm, was analyzed using a venous flow simulator. RESULTS: When ≥4 × 10-mm clots were used, the CCEs were 100% for all four types of IVC filters in a 20-mm-diameter simulated IVC filter. However, when ≤3 × 20-mm clots were used, the CCEs were significantly different among the four types of filters in a 20-mm-diameter simulated IVC, with the Denali showing the highest CCE, followed by the OptEase, Celect, and Option. When ≥6 × 10-mm clots were used, the CCEs were 100% for all four types of IVC filters in the 25-mm-diameter simulated IVC. However, when ≤5 × 20-mm clots were used, the CCEs were significantly different among the four types of filters in the 25-mm-diameter simulated IVC, with the Denali showing the highest CCE. When ≤5 × 10-mm clots were used, the CCEs were significantly lower in the 25-mm-diameter simulated IVC than in the 20-mm-diameter simulated IVC for all four types of IVC filters, with Option showing the greatest change in CCEs, followed by the Celect, OptEase, and Denali. CONCLUSIONS: The CCEs were significantly different among the four IVC filters and were significantly lower for the smaller size clots than for the larger size clots and for the larger diameter simulated IVC than for the smaller diameter simulated IVC.


Assuntos
Implantação de Prótese/instrumentação , Filtros de Veia Cava , Tromboembolia Venosa/prevenção & controle , Trombose Venosa/terapia , Animais , Remoção de Dispositivo , Teste de Materiais , Desenho de Prótese , Sus scrofa , Tromboembolia Venosa/sangue , Trombose Venosa/sangue
11.
J Endocrinol Invest ; 45(1): 9-16, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34115342

RESUMO

OBJECTIVE: Patients with Cushing's syndrome (CS) are at high risk of venous thromboembolism related to a hypercoagulability due to procoagulant imbalance. However, whether these alterations are reversible after disease remission is still unclear. The endogenous thrombin potential (ETP) measured with and without the addition of thrombomodulin provides a global representation of coagulation and previous data confirmed hypercoagulable profile in patients with active hypercortisolism. Aim of this study was to assess the short- and long-term modification of ETP in patients with CS after disease remission. DESIGN AND METHODS: Nineteen patients with CS for whom surgical remission was achieved, were prospectively evaluated for clinical characteristics, cortisol secretion profile and ETP at different time points: (i) before surgical intervention; (ii) after 6 months and (iii) 5 years from the time of persistent remission. Nineteen healthy subjects matched for age and gender were also evaluated as control group. RESULTS: Before surgery, patients showed higher ETP-ratio (with/without thrombomodulin) than controls (0.62 ± 0.09-vs-0.56 ± 0.09, p = 0.034). No significant correlation between ETP-ratio and cortisol secretion was found. 6 months after remission, ETP-ratio was still significantly increased compared to controls (0.64 ± 0.09-vs-0.56 ± 0.09, p = 0.01), but was similar to baseline (0.64 ± 0.09-vs-0.62 ± 0.09, p = 0.87). At 5 years, ETP-ratio showed a significant decrease (0.55 ± 0.14-vs-0.62 ± 0.09, p = 0.02) and was comparable to controls (0.55 ± 0.14-vs-0.56 ± 0.09, p = 0.7). CONCLUSIONS: Plasma hypercoagulability detected in patients with active hypercortisolism persists at short-term evaluation and seems to be completely reversible after long-term remission of disease. These data, as part of a whole evaluation of thrombotic risk, can contribute to make appropriate therapeutic choice in these patients.


Assuntos
Testes de Coagulação Sanguínea/métodos , Síndrome de Cushing , Hidrocortisona/sangue , Trombina/análise , Trombofilia , Tromboembolia Venosa , Adrenalectomia/métodos , Adulto , Coagulação Sanguínea , Síndrome de Cushing/sangue , Síndrome de Cushing/complicações , Síndrome de Cushing/cirurgia , Feminino , Humanos , Hipofisectomia/métodos , Masculino , Período Pós-Operatório , Indução de Remissão , Medição de Risco/métodos , Trombofilia/sangue , Trombofilia/etiologia , Tempo , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
12.
JAMA ; 326(21): 2141-2149, 2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34874418

RESUMO

Importance: Uncontrolled studies suggest that pulmonary embolism (PE) can be safely ruled out using the YEARS rule, a diagnostic strategy that uses varying D-dimer thresholds. Objective: To prospectively validate the safety of a strategy that combines the YEARS rule with the pulmonary embolism rule-out criteria (PERC) rule and an age-adjusted D-dimer threshold. Design, Settings, and Participants: A cluster-randomized, crossover, noninferiority trial in 18 emergency departments (EDs) in France and Spain. Patients (N = 1414) who had a low clinical risk of PE not excluded by the PERC rule or a subjective clinical intermediate risk of PE were included from October 2019 to June 2020, and followed up until October 2020. Interventions: Each center was randomized for the sequence of intervention periods. In the intervention period (726 patients), PE was excluded without chest imaging in patients with no YEARS criteria and a D-dimer level less than 1000 ng/mL and in patients with 1 or more YEARS criteria and a D-dimer level less than the age-adjusted threshold (500 ng/mL if age <50 years or age in years × 10 in patients ≥50 years). In the control period (688 patients), PE was excluded without chest imaging if the D-dimer level was less than the age-adjusted threshold. Main Outcomes and Measures: The primary end point was venous thromboembolism (VTE) at 3 months. The noninferiority margin was set at 1.35%. There were 8 secondary end points, including chest imaging, ED length of stay, hospital admission, nonindicated anticoagulation treatment, all-cause death, and all-cause readmission at 3 months. Results: Of the 1414 included patients (mean age, 55 years; 58% female), 1217 (86%) were analyzed in the per-protocol analysis. PE was diagnosed in the ED in 100 patients (7.1%). At 3 months, VTE was diagnosed in 1 patient in the intervention group (0.15% [95% CI, 0.0% to 0.86%]) vs 5 patients in the control group (0.80% [95% CI, 0.26% to 1.86%]) (adjusted difference, -0.64% [1-sided 97.5% CI, -∞ to 0.21%], within the noninferiority margin). Of the 6 analyzed secondary end points, only 2 showed a statistically significant difference in the intervention group compared with the control group: chest imaging (30.4% vs 40.0%; adjusted difference, -8.7% [95% CI, -13.8% to -3.5%]) and ED median length of stay (6 hours [IQR, 4 to 8 hours] vs 6 hours [IQR, 5 to 9 hours]; adjusted difference, -1.6 hours [95% CI, -2.3 to -0.9]). Conclusions and Relevance: Among ED patients with suspected PE, the use of the YEARS rule combined with the age-adjusted D-dimer threshold in PERC-positive patients, compared with a conventional diagnostic strategy, did not result in an inferior rate of thromboembolic events. Trial Registration: ClinicalTrials.gov Identifier: NCT04032769.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Embolia Pulmonar/diagnóstico , Tromboembolia Venosa/diagnóstico , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Causas de Morte , Intervalos de Confiança , Estudos Cross-Over , Serviço Hospitalar de Emergência , Feminino , França , Hospitalização/estatística & dados numéricos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Estudos Prospectivos , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/mortalidade , Reprodutibilidade dos Testes , Espanha , Tromboembolia Venosa/sangue , Adulto Jovem
13.
Bioengineered ; 12(2): 11156-11168, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34783290

RESUMO

Venous thromboembolism (VTE) is the third most prevalent cardiovascular complication. Increasing studies have demonstrated that some microRNAs (miRNAs) are aberrantly expressed in VTE and play crucial roles in mediating the development of VTE. Therefore, our study intends to explore the detailed function and molecular mechanism of miR-200c-3p in VTE progression. In our research, VTE rat models were first established via inferior vena cava (IVC) ligation and the time-dependent effects of IVC ligation on thrombus formation were discovered. The results of reverse transcription quantitative polymerase-chain reaction (RT-qPCR) and western blotting showed that serpin family C member 1 (SERPINC1) was downregulated in VTE rat models and showed an inverse correlation with thrombus load. MiRNA target prediction tools and luciferase reporter assay confirmed SERPINC1 as a target for miR-200c-3p. VTE rats were injected with miR-200c-3p inhibitor for 24 h to investigate whether miR-200c-3p knockdown influences thrombus formation in vivo. Histological examination through hematoxylin-eosin staining revealed that miR-200c-3p downregulation markedly inhibited the formation of thrombus in IVC of rats. Additionally, miR-200c-3p was upregulated while SERPINC1 was downregulated in serum and inferior vena cava of VTE rats as well as in plasma of patients with VTE. Linear regression analysis demonstrated that miR-200c-3p expression was negatively correlated to SERPINC1 expression in VTE rats and patients with VTE. Our study determines the previously unelucidated function of miR-200c-3p in VTE, which might provide a potential novel insight for the treatment of VTE.


Assuntos
Antitrombina III/metabolismo , Regulação para Baixo/genética , MicroRNAs/genética , Tromboembolia Venosa/genética , Regiões 3' não Traduzidas/genética , Animais , Antitrombina III/genética , Sequência de Bases , Modelos Animais de Doenças , Feminino , Células HEK293 , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Ratos Sprague-Dawley , Trombose/patologia , Tromboembolia Venosa/sangue
14.
Isr Med Assoc J ; 23(10): 635-638, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34672445

RESUMO

BACKGROUND: Venous thromboembolism (VTE) is a serious disease, which demands a fast accurate diagnosis to begin suitable treatment. It presents a major problem in the emergency department (ED), and its confirmation requires adequate evaluation. OBJECTIVES: To evaluate a potential role of mean platelet volume (MPV) in differentiating VTE from other potential diagnosis in patients with suspected VTE. METHODS: We conducted a retrospective case-controlled study of 440 consecutive patients who presented to the ED of our hospital with clinical VTE, but only 316 with proven VTE. A control group was composed of patients (124) who presented with clinical VTE but without proven VTE. We checked the MPV value in all 440 patients and the correlation with VTE occurrence in the study group vs. control group. RESULTS: Statistical analysis of the acquired results indicated that MPV value could not aid in determining the difference of real VTE vs. patients with VTE-like clinical picture presenting to the ED. We found an inverse correlation between MPV value and proven VTE, in contrast to most researchers who have studied the same issue. CONCLUSIONS: Although MPV can be a useful diagnostic marker in many diseases, we found no definite association between low MPV and VTE.


Assuntos
Diagnóstico Precoce , Volume Plaquetário Médio/métodos , Tromboembolia Venosa , Estudos de Casos e Controles , Diagnóstico Diferencial , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Resultados Negativos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tempo para o Tratamento , Tromboembolia Venosa/sangue , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia
15.
JAMA Neurol ; 78(11): 1314-1323, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34581763

RESUMO

Importance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson). Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS. Design, Setting, and Participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination. Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria. Main Outcomes and Measures: Clinical characteristics and mortality rate. Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later. Conclusions and Relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.


Assuntos
Vacinas contra COVID-19/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/mortalidade , Sistema de Registros , Trombose dos Seios Intracranianos/mortalidade , Trombocitopenia/mortalidade , Tromboembolia Venosa/mortalidade , Adulto , Idoso , Vacinas contra COVID-19/efeitos adversos , Estudos de Coortes , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Fatores Sexuais , Trombose dos Seios Intracranianos/sangue , Trombose dos Seios Intracranianos/induzido quimicamente , Síndrome , Trombocitopenia/sangue , Trombocitopenia/induzido quimicamente , Tromboembolia Venosa/sangue , Tromboembolia Venosa/induzido quimicamente , Adulto Jovem
16.
Arterioscler Thromb Vasc Biol ; 41(11): 2681-2692, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34496636

RESUMO

The immunoglobulin receptor GPVI (glycoprotein VI) is selectively expressed on megakaryocytes and platelets and is currently recognized as a receptor for not only collagen but also a variety of plasma and vascular proteins, including fibrin, fibrinogen, laminin, fibronectin, and galectin-3. Deficiency of GPVI is protective in mouse models of experimental thrombosis, pulmonary thromboembolism as well as in thromboinflammation, suggesting a role of GPVI in arterial and venous thrombus formation. In humans, platelet GPVI deficiency is associated with a mild bleeding phenotype, whereas a common variant rs1613662 in the GP6 gene is considered a risk factor for venous thromboembolism. However, preclinical studies on the inhibition of GPVI-ligand interactions are focused on arterial thrombotic complications. In this review we discuss the emerging evidence for GPVI in venous thrombus formation and leukocyte-dependent thromboinflammation, extending to venous thromboembolism, pulmonary thromboembolism, and cancer metastasis. We also recapitulate indications for circulating soluble GPVI as a biomarker of thrombosis-related complications. Collectively, we conclude that the current evidence suggests that platelet GPVI is also a suitable cotarget in the prevention of venous thrombosis due to its role in thrombus consolidation and platelet-leukocyte complex formation.


Assuntos
Coagulação Sanguínea , Plaquetas/metabolismo , Inflamação/metabolismo , Ativação Plaquetária , Glicoproteínas da Membrana de Plaquetas/metabolismo , Tromboembolia Venosa/metabolismo , Trombose Venosa/metabolismo , Animais , Anti-Inflamatórios/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Plaquetas/patologia , Fibrinolíticos/uso terapêutico , Humanos , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/patologia , Mediadores da Inflamação/sangue , Ligantes , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/uso terapêutico , Glicoproteínas da Membrana de Plaquetas/antagonistas & inibidores , Transdução de Sinais , Tromboembolia Venosa/sangue , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/patologia , Trombose Venosa/sangue , Trombose Venosa/tratamento farmacológico , Trombose Venosa/patologia
17.
Arterioscler Thromb Vasc Biol ; 41(11): 2837-2847, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34470475

RESUMO

Objective: Pancreatic cancer activates coagulation and increases risk of venous thromboembolism (VTE). We aimed at characterizing the association of hemostatic biomarkers and VTE with mortality and chemotherapy response. Approach and Results: Pancreatic cancer patients (N=145) were included in a prospective, observational cohort study (CATS [Vienna Cancer and Thrombosis Study]). Hemostatic biomarkers (D-dimer, extracellular vesicle-tissue factor activity, prothrombin fragment 1+2, fibrinogen, factor VIII, PAI-1 [plasminogen activator inhibitor 1], sP-selectin [soluble P-selectin], thrombin generation assay) were measured at inclusion. The impact of VTE on overall survival/progression-free survival (OS/PFS) was evaluated by multistate modeling. The association of biomarkers with OS was analyzed by Cox-regression and with PFS and disease control rate in patients initiating palliative chemotherapy (n=95) by Cox-regression and logistic regression. Multivariable analysis included stage, grade, sex, age, performance status, VTE (time-dependent), vascular infiltration/compression, and tumor marker levels (carbohydrate-antigen 19-9, carcinoembryonic antigen). VTE occurrence was associated with shorter OS (transition hazard ratio, 3.40 [95% CI, 2.05-5.64]) and shorter PFS (transition hazard ratio, 2.10 [1.16-3.79]). Median post-VTE OS/PFS in months was 5.5 [2.2-6.5] and 3.0 [1.5-3.9], compared with 13.4 [9.7-16.6] and 7.5 [5.9-9.8] in patients without VTE (both P<0.001). D-dimer, extracellular vesicle-tissue factor activity, PAI-1, and sP-selectin were associated with increased mortality (hazard ratio per doubling, 1.27 [1.00-1.61]; 1.63 [1.14-2.36]; 1.25 [1.06-1.47]; 1.52 [1.05-2.20]). In patients initiating palliative chemotherapy, higher D-dimer predicted shorter PFS (hazard ratio per doubling, 1.27 [1.01-1.60]) and lower disease control rate (odds ratio per doubling, 0.59 [0.36-0.98]). Conclusions: VTE diagnosis is associated with shorter OS and PFS. Higher baseline levels of D-dimer, extracellular vesicle-tissue factor activity, PAI-1, and sP-selectin were independently prognostic for increased mortality, and D-dimer predicted response to palliative chemotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Hemostasia , Neoplasias Pancreáticas/tratamento farmacológico , Tromboembolia Venosa/sangue , Idoso , Anticoagulantes/uso terapêutico , Antineoplásicos/efeitos adversos , Biomarcadores/sangue , Progressão da Doença , Vesículas Extracelulares/metabolismo , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Selectina-P/sangue , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Inibidor 1 de Ativador de Plasminogênio/sangue , Intervalo Livre de Progressão , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Tromboplastina/metabolismo , Fatores de Tempo , Resultado do Tratamento , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/mortalidade
18.
Blood Coagul Fibrinolysis ; 32(6): 382-386, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34397449

RESUMO

The aim of the study was to compare age at first venous thromboembolism (VTE), plasma homocysteine and activated partial thromboplastin time ratio (aPTTr) amongst unprovoked VTE patients with the methylentetrahydrofolate reductase (MTHFR) C667T genotypes, and to identify predictors of age at first VTE, of plasma homocysteine and of the aPTTr; to evaluate whether heterozygous or homozygous prothrombin (PT) G20210A mutation lowered the age at first VTE when associated with MTHFR TT. Retrospective cohort study on 259 MTHFR TT, 76 MTHFR TC and 64 MTHFR CC participants with unprovoked VTE; each participant contributed age, sex, age at VTE, history of dyslipidaemia, hypertension, smoking, homocysteine (measured by enzyme immunoassay) and aPTTr (measured by standard coagulation assay). Age at first VTE was lower in MTHFR TT than MTHFR TC and CC (41 ±â€Š14 vs. 50 ±â€Š16 vs. 51 ±â€Š12 years, respectively, P < 0.0001); plasma homocysteine was higher in MTHFR TT than in the other groups (22 ±â€Š21 vs. 12 ±â€Š11.6 vs. 10 ±â€Š3.3 µmol/l, respectively, P = 0.0005) whilst aPTTr was not different. MTHFR TT independently predicted age at first VTE (P = 0.001), plasma homocysteine (P < 0.0001) alongside sex (P = 0.0007), age and smoking (P = 0.03 for both). Compound MTHFR TT with PT GA or AA had no lowering effect on age at first VTE compared with MTHFR TT alone (41 ±â€Š13 vs. 41 ±â€Š14 years). Plasma homocysteine inversely related to aPTTr in the MTHFR TT group (P = 0.003). MTHFR TT anticipates age at first VTE by an average of 10 years compared with MTHFR TC and CC genotypes.


Assuntos
Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Tromboembolia Venosa/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Coagulação Sanguínea , Feminino , Homocisteína/sangue , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação Puntual , Estudos Retrospectivos , Tromboembolia Venosa/sangue , Tromboembolia Venosa/epidemiologia
19.
Blood ; 138(21): 2129-2137, 2021 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-34339498

RESUMO

The role of complement in the pathogenesis of venous thromboembolism (VTE) is unclear. We wanted to investigate (1) whether plasma complement component C5 (C5) levels are influenced by genetic variants or chronic inflammation and (2) the association between plasma C5 and risk of future VTE in a nested case-control study of 415 patients with VTE and 848 age- and sex-matched controls derived from the Tromsø Study. Plasma C5 levels were measured at inclusion. Odds ratios (ORs) with 95% confidence intervals (95% CIs) for provoked and unprovoked VTE across tertiles of C5 concentrations were estimated by logistic regression. Adjustment for C-reactive protein (CRP) served as a proxy for general inflammation. Whole-exome sequencing and protein quantitative trait loci analyses were performed to assess genetic influence on C5 concentrations. There was no association between genome-wide or C5-related gene variants and C5 levels. The association between plasma C5 levels and VTE risk displayed a threshold effect, where subjects with C5 levels above the lowest tertile had increased risk of VTE. Subjects in tertile 3 (highest C5 levels) had an age- and sex-adjusted OR of 1.45 (95% CI, 1.07-1.96) compared with tertile 1 (lowest). These statistics were more pronounced for unprovoked VTE (OR, 1.70; 95% CI, 1.11-2.60). Adjustments for body mass index and CRP had minor impact on risk estimates. The OR increased substantially with shorter time between blood sampling and VTE event. In conclusion, plasma C5 was associated with risk of future VTE. C5 levels were not genetically regulated and were only slightly influenced by chronic inflammation.


Assuntos
Complemento C5/análise , Tromboembolia Venosa/sangue , Idoso , Estudos de Casos e Controles , Doença Crônica , Complemento C5/genética , Feminino , Variação Genética , Humanos , Inflamação/sangue , Inflamação/genética , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Tromboembolia Venosa/genética , Tromboembolia Venosa/patologia
20.
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
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