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BACKGROUND: Hypercoagulable state is considered a common complication in brain tumors, which increases the risk of thromboembolic events, leading to mortality and morbidities. Detecting hypercoagulability typically requires expensive tests, such as D-dimer and fibrinogen, which are not accessible in many healthcare facilities in Indonesia. The systemic immune-inflammation index (SII) is known as an inflammation marker that contributes to hypercoagulability in many conditions. SII tests are more affordable and widely available, but there is still not much study that investigates the association between SII and hypercoagulable state in primary brain tumors. This preliminary study aimed to find an association between SII with hypercoagulable state in primary brain tumor conditions. METHODS: We collected data from inpatients diagnosed with primary brain tumors from 2021 to 2023 in Dr. Cipto Mangunkusumo Hospital. Hypercoagulable states were established from high D-dimer serum testing (>660 µg/L). SII was calculated by the following formula: neutrophil counts × platelet counts/lymphocyte counts. Both D-dimer and SII were collected at first admission to the hospital. The receiver operating characteristic (ROC) curve were used to determine the SII cut-off value. Bivariate and multivariate logistic analyses were performed to confirm the association with the incidence of hypercoagulable state. RESULTS: This study enrolled 65 patients with primary brain tumors, 73.8% subjects with hypercoagulable state. A total of 61.5% were female, mean age 47.54±2.02 years. High-grade tumors exhibited a higher prevalence than low-grade tumors (53.8% vs. 46.2%). SII cut-off value determined at 1,343.50 (sensitivity 56.9%, specificity 57.1%). We found no significant association between SII and hypercoagulable state. Multivariate analyses show that duration of brain tumor before 6 months (P=0.04), and history of brain tumor surgery (P=0.02) were significantly associated with the incidence of hypercoagulable state in primary brain tumor. CONCLUSIONS: Based on the findings in this investigation, we find 73.8% subjects with hypercoagulable states in primary brain tumor. No significant relationship between high SII and hypercoagulable states but significant association of duration brain tumor before 6 months and history of brain tumor surgery with hypercoagulable state in primary brain tumor.
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Neoplasias Encefálicas , Trombofilia , Humanos , Feminino , Masculino , Estudos Retrospectivos , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/sangue , Indonésia , Pessoa de Meia-Idade , Trombofilia/sangue , Inflamação , Adulto , IdosoRESUMO
OBJECTIVES: Individuals with pelvic and acetabular fractures are at high risk of venous thromboembolism (VTE). The purpose of this study was to determine whether serum markers for thrombophilia and rapid thromboelastography (r-TEG) values correlate with increased VTE risk among patients with pelvic and acetabular fractures. METHODS: . DESIGN: Prospective observational study. SETTING: Two urban academic level 1 trauma centers. PATIENT SELECTION CRITERIA: Adult patients with isolated pelvis and/or acetabulum fractures (OTA/AO 61 and 62) treated surgically placed on a standardized VTE chemoprophylaxis regimen with enoxaparin over a 5-year period were included. OUTCOME MEASURES AND COMPARISONS: Serum r-TEG, coagulation laboratory values, and markers for heritable thrombophilia were drawn postoperatively and after completion of a 6-week course of enoxaparin. The primary outcome was VTE event (either deep venous thrombosis or pulmonary embolism) diagnosed using a Duplex ultrasound, chest computed tomography angiogram, or lung ventilation-perfusion ordered based on clinical suspicion of a VTE event. Laboratory markers and values were then compared between patients who went on to have a VTE event and those who did not and patients with and without markers of thrombophilia. RESULTS: One hundred thirty-three adult patients with isolated operative pelvic and/or acetabular fractures were enrolled in this study. The average age of patients at time of injury was 48.3 years (range 18-91). Sixty-seven percent of patients in the study were (n = 90) males. Sixty-three percent of patients (n = 84) completed both clinical and laboratory follow-up. Forty-one percent of patients (n = 54) had 1 or more markers of heritable thrombophilia. Twelve percent (n = 10) of patients who completed follow-up were diagnosed with VTE. Age, sex, and smoking status were not associated with VTE. Patients who developed VTE had a higher body mass index (P = 0.04). Having more than 1 marker of heritable thrombophilia (P = 0.004) and an r-TEG mean amplitude greater than 72 mm postoperatively was positively associated with VTE (P = 0.02). CONCLUSIONS: Among patients treated surgically for isolated pelvic and acetabular fractures who received enoxaparin prophylaxis, the presence of more than 1 marker of heritable thrombophilia or r-TEG mean amplitude value greater than 72 mm postoperatively was associated with an increased risk of VTE. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
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Acetábulo , Fraturas Ósseas , Ossos Pélvicos , Trombofilia , Tromboembolia Venosa , Humanos , Masculino , Acetábulo/lesões , Feminino , Trombofilia/complicações , Trombofilia/sangue , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/etiologia , Fraturas Ósseas/complicações , Fraturas Ósseas/cirurgia , Adulto , Pessoa de Meia-Idade , Ossos Pélvicos/lesões , Estudos Prospectivos , Enoxaparina/uso terapêutico , Anticoagulantes/uso terapêutico , Fatores de Risco , Idoso , Adulto Jovem , Comorbidade , Medição de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Cholestatic liver diseases induce local and systemic hypercoagulation, with neutrophil extracellular traps (NETs) serving as major drivers. These NETs have been linked to decreased liver function in patients with obstructive jaundice. However, the impact of NETs on liver hypercoagulation in cholestatic liver disease remains unknown. METHODS: We utilized bile duct ligation to create experimental mice and analyzed NETs formation in the liver. Fibrin deposition, tissue factor expression, and inflammation in the liver were visualized through western blot and immunohistochemical techniques. LSECs were incubated with isolated NETs, and we detected endothelial procoagulant activity using coagulation protein production assays and measuring endothelial permeability. In both in vivo and in vitro settings, DNase I was applied to clarify the effect of NETs on intrahepatic hypercoagulability, hepatotoxicity, LSEC, and macrophage activation or injury. RESULTS: Bile duct ligation mice exhibited significantly increased levels of NETs in liver tissue, accompanied by neutrophil infiltration, tissue necrosis, fibrin deposition, and thrombophilia compared to sham mice. Notably, NETs resulted in phosphatidylserine and tissue factor exposure on LSEC, enhancing coagulation Factor Xa and thrombin production. The enhanced procoagulant activity could be reversed by degrading NETs with DNase I. Additionally, NETs-induced permeability changes in LSECs, characterized by increased VE-cadherin expression and F-actin retraction, which could be rescued by DNase I. Meanwhile, NET formation is associated with KC activation and the formation of inflammatory factors. CONCLUSIONS: NETs promote intrahepatic activation of coagulation and inflammation, leading to liver tissue injury. Strategies targeting NET formation may offer a potential therapeutic approach for treating cholestatic liver disease.
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Armadilhas Extracelulares , Fígado , Trombose , Armadilhas Extracelulares/metabolismo , Animais , Camundongos , Fígado/patologia , Fígado/metabolismo , Trombose/etiologia , Trombose/patologia , Colestase/patologia , Colestase/complicações , Modelos Animais de Doenças , Masculino , Tromboplastina/metabolismo , Trombofilia/etiologia , Trombofilia/sangue , Fibrina/metabolismo , Camundongos Endogâmicos C57BL , Neutrófilos/metabolismo , Humanos , Infiltração de Neutrófilos , Fator Xa/metabolismo , Trombina/metabolismoRESUMO
BACKGROUND: Nephrotic syndrome (NS) is associated with a high risk of thrombotic complications. In this group of patients, routine local tests for assessing hemostasis do not accurately reflect hypercoagulable state. Global functional tests for assessing hemostasis, including thrombodynamics (TD), are considered promising for assessing disorders in the blood coagulation system of these patients. AIM: To compare the rate of hypercoagulability according to routine hemostatic tests and TD and to evaluate the factors associated with increased risk of thrombotic complications in patients with chronic glomerulonephritis (CGN). MATERIALS AND METHODS: The study included 94 patients with active CGN who were not receiving anticoagulant therapy; 63 (80.3%) patients had NS, and 31 (19.7%) had active CGN without NS. Hemostasis parameters were assessed using local coagulation tests and TD test. Using logistic regression analysis, factors associated with the risk of thrombosis were assessed. RESULTS: Of the 94 patients with active CGN in 63 without preventive anticoagulant therapy, hypercoagulability according to routine tests was detected in 6 (9.5%) patients with NS and in 3 (9.7%) patients without NS (p<0.05). Hypercoagulability according to the TD test was detected in 24 (53.9%) patients with NS and in 5 (32.2%) without NS (p<0.05). The formation of spontaneous clots was observed in 29 (30.9%) of patients with CGN, most of them 24 (83%) with NS. 10.6% of patients in our cohort experienced thromboembolic events. The risk of thromboembolic events according to the univariate regression analysis was associated with older age, higher lipid levels, use of glucocorticosteroids and detection of spontaneous clots by the TD test. No association of thromboembolic events with abnormalities in routine hemostasis tests was obtained. CONCLUSION: In patients with CGN with nephrotic syndrome, hypercoagulability is detected in 9.5% of cases with routine coagulation tests and in 53.9% of cases with TD test. Detection of spontaneous clots by TD test is associated with a risk of thromboembolic events.
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Glomerulonefrite , Trombofilia , Humanos , Masculino , Feminino , Trombofilia/sangue , Trombofilia/diagnóstico , Trombofilia/etiologia , Glomerulonefrite/sangue , Glomerulonefrite/complicações , Glomerulonefrite/diagnóstico , Adulto , Pessoa de Meia-Idade , Testes de Coagulação Sanguínea/métodos , Hemostasia/fisiologia , Doença Crônica , Síndrome Nefrótica/complicações , Síndrome Nefrótica/sangue , Síndrome Nefrótica/diagnósticoRESUMO
The circadian system regulates 24-h time-of-day patterns of cardiovascular physiology, with circadian misalignment resulting in adverse cardiovascular risk. Although many proteins in the coagulation-fibrinolysis axis show 24-h time-of-day patterns, it is not understood if these temporal patterns are regulated by circadian or behavioral (e.g., sleep and food intake) cycles, or how circadian misalignment influences these patterns. Thus, we utilized a night shiftwork protocol to analyze circadian versus behavioral cycle regulation of 238 plasma proteins linked to cardiovascular physiology. Six healthy men aged 26.2 ± 5.6 years (mean ± SD) completed the protocol involving two baseline days with 8-h nighttime sleep opportunities (circadian alignment), a transition to shiftwork day, followed by 2 days of simulated night shiftwork with 8-h daytime sleep opportunities (circadian misalignment). Plasma was collected for proteomics every 4 h across 24 h during baseline and during daytime sleep and the second night shift. Cosinor analyses identified proteins with circadian or behavioral cycle-regulated 24-h time-of-day patterns. Five proteins were circadian regulated (plasminogen activator inhibitor-1, angiopoietin-2, insulin-like growth factor binding protein-4, follistatin-related protein-3, and endoplasmic reticulum resident protein-29). No cardiovascular-related proteins showed regulation by behavioral cycles. Within the coagulation pathway, circadian misalignment decreased tissue factor pathway inhibitor, increased tissue factor, and induced a 24-h time-of-day pattern in coagulation factor VII (all FDR < 0.10). Such changes in protein abundance are consistent with changes observed in hypercoagulable states. Our analyses identify circadian regulation of proteins involved in cardiovascular physiology and indicate that acute circadian misalignment could promote a hypercoagulable state, possibly contributing to elevated cardiovascular disease risk among shift workers.
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Biomarcadores , Doenças Cardiovasculares , Ritmo Circadiano , Humanos , Masculino , Adulto , Ritmo Circadiano/fisiologia , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/metabolismo , Biomarcadores/sangue , Jornada de Trabalho em Turnos , Adulto Jovem , Trombofilia/sangue , Trombofilia/fisiopatologia , Coagulação Sanguínea/fisiologia , Sono/fisiologiaRESUMO
Cancer-associated thrombosis (CAT) is a common complication and a major cause of morbidity and mortality in patients with active cancers. CAT is common in various malignancies, particularly pancreatic, ovarian, gastric, colorectal, and hematologic cancers. In fact, CAT is a complicated multifactorial complication that may be influenced by the type of cancer as well as by the genetic background and inheritance of thrombophilic variants and elevated concentrations of coagulation factors. Several studies have shown the prominent role of inherited thrombophilias, such as prothrombin 20210, factor V Leiden, factor XIII Val34Leu, MTHFR C677T, in the occurrence of CAT, while others have found no correlation between them and CAT. In the present review, we have attempted to investigate the possible role of inherited thrombophilia in the occurrence of CAT.
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Neoplasias , Trombofilia , Trombose , Humanos , Trombofilia/complicações , Trombofilia/genética , Trombofilia/sangue , Neoplasias/complicações , Neoplasias/genética , Neoplasias/sangue , Trombose/etiologia , Fator V/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genéticaRESUMO
BACKGROUND: Migraine is associated with several genetic or acquired comorbidities. Studies conducted in recent years emphasize that the frequency of thrombophilia is high in migraine, especially migraine with aura (MA). Similarly, the presence of white matter lesions (WMLs) on brain magnetic resonance imaging (MRI) scans has been associated with migraine for many years. OBJECTIVE: Based on the knowledge that both WMLs and thrombophilia variants are frequently observed in MA, we aimed to investigate whether there is a relationship between genetic thrombophilia and the presence of WMLs in these patients. METHODS: The levels of proteins S and C, antithrombin III activities, activated protein C (APC) resistance, antiphospholipid immunoglobulin G/immunoglobulin M (IgG/IgM) and anticardiolipin IgG/IgM antibodies were investigated in 66 MA patients between the ages of 18 and 49 years who presented no cardiovascular risk factors. The presence of WMLs and the Fazekas grade was determined from the brain magnetic resonance imaging (MRI) scans' T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequence taken from the patients. The rates of WMLs were compared in patients with and without thrombophilia. RESULTS: Thrombophilia was detected in 34.8% of the patients, and 27.3% were determined to have WMLs in brain MRI scans. The WMLs were detected in 23.3% of the patients without thrombophilia, in 34.8% of those with thrombophilia, and in 50% of the subjects with multiple thrombophilia disorders. Among the thrombophilia disorders, only APC resistance was significantly more common in patients with WMLs. CONCLUSION: The results of the present study showed that thrombophilia may be a mechanism that should be investigated in the etiology of increased WMLs in MA.
ANTECEDENTES: La migraña se asocia con una serie de comorbilidades genéticas o adquiridas. Los estudios realizados en los últimos años destacan que la frecuencia de trombofilia es elevada en la migraña, especialmente en la migraña con aura (MA). De manera similar, la presencia de lesiones de la sustancia blanca (LSB) en las imágenes por resonancia magnética (RM) del cerebro se ha asociado con la migraña hace muchos años. OBJETIVO: Con base en la información de que se suelen observar tanto LSB como variantes de la trombofilia en MA, nuestro objetivo fue investigar si existe una relación entre la trombofilia genética y la presencia de LSB en estos pacientes. MéTODOS: Se investigaron los niveles de proteína S y de proteína C, actividades de antitrombina III, resistencia a la proteína C activada (PCA), anticuerpos antifosfolípidos inmunoglobulina G/inmunoglobulina M (IgG/IgM) y anticuerpos anticardiolipina IgG/IgM en 66 pacientes con MA entre 18 y 49 años que no presentaban factores de riesgo cardiovascular. Se determinaron la presencia de LSB y el grado de Fazekas a partir de imágenes por RM del cerebro en la secuencia ponderada en T2 y recuperación de la inversión atenuada de fluido (fluid-attenuated inversion recovery, FLAIR, en inglés) obtenidas de los pacientes. Se compararon las tasas de LSB en pacientes con y sin trombofilia. RESULTADOS: Se detectó trombofilia en el 34,8% de los pacientes y LSB en el 27,3%. Las LSB estuvieron presentes en el 23,3% de los pacientes sin trombofilia, en el 34,8% de los que tenían trombofilia, y en el 50% de los que tenían múltiples trastornos trombofílicos. La resistencia a la PCA fue significativamente más común en aquellos pacientes con LSB. CONCLUSIóN: Los resultados del presente estudio mostraron que la trombofilia puede ser un mecanismo que debe investigarse en la etiología del aumento de LSB en MA.
Assuntos
Imageamento por Ressonância Magnética , Enxaqueca com Aura , Trombofilia , Substância Branca , Humanos , Adulto , Feminino , Masculino , Trombofilia/sangue , Pessoa de Meia-Idade , Enxaqueca com Aura/diagnóstico por imagem , Enxaqueca com Aura/sangue , Adulto Jovem , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adolescente , Antitrombina III/análise , Proteína S/análise , Fatores de Risco , Anticorpos Anticardiolipina/sangue , Proteína C/análise , Imunoglobulina G/sangue , Anticorpos Antifosfolipídeos/sangueRESUMO
INTRODUCTION: There is good evidence that specific autoimmune rheumatic diseases (RDs), for example, rheumatoid arthritis and systemic lupus erythematosus (SLE), are associated with a state of hypercoagulability and an increased risk of venous thromboembolism (VTE). However, limited information regarding this association is available for other autoimmune or autoinflammatory RDs. We sought to address this issue by conducting a systematic review and meta-analysis of the association between the d-dimer, an established marker of hypercoagulability and VTE, and RDs and the possible clinical and demographic factors mediating this association. METHODS: We searched the electronic databases PubMed, Web of Science, and Scopus from inception to January 31, 2024. The risk of bias and the certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and GRADE, respectively. RESULTS: In 31 studies selected for analysis (2724 RD patients and 3437 healthy controls), RD patients had overall significantly higher d-dimer concentrations when compared to controls (standard mean difference = 0.93, 95% CI 0.76-1.10, p < .001; I2 = 86.1%, p < .001; moderate certainty of evidence). The results were stable in a sensitivity analysis. Significant associations were observed between the effect size of the between-group differences in d-dimer concentration and age, specific RD and RD category, RD duration, fibrinogen, plasminogen activator inhibitor, C-reactive protein, and erythrocyte sedimentation rate. CONCLUSIONS: Overall, patients with RDs have significantly higher d-dimer concentrations when compared with healthy controls, indicating a state of hypercoagulability. The alterations in d-dimer concentrations are mediated by age, specific RD and RD category, RD duration, and markers of anticoagulation and inflammation. Further research is warranted to investigate d-dimer concentrations across the spectrum of RDs and their utility in predicting and managing VTE in these patients (PROSPERO registration number: CRD42024517712).
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Biomarcadores , Produtos de Degradação da Fibrina e do Fibrinogênio , Doenças Reumáticas , Tromboembolia Venosa , Humanos , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Doenças Reumáticas/sangue , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/complicações , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/diagnóstico , Biomarcadores/sangue , Trombofilia/sangue , Trombofilia/etiologia , Trombofilia/diagnósticoRESUMO
BACKGROUND: Patients with idiopathic membranous nephropathy (IMN) are more likely to be complicated by venous thromboembolism (VTE). The aim of the study was to investigate the potential association between anti-phospholipase A2 receptor (PLA2R) antibodies and hypercoagulability in patients with IMN. METHODS: A total of 168 patients with biopsy-proven IMN and 36 patients with biopsy-proven minimal change disease (MCD) were enrolled in this study. The clinical data, serum anti-PLA2R antibodies and coagulation-related indices of the patients were retrospectively analyzed. RESULTS: Patients with IMN were categorized into glomerular PLA2R staining-positive (GAg+) IMN group and glomerular PLA2R staining-negative (GAg-) IMN group in the study. Patients with IMN who were GAg + had lower PT, APTT and R time than patients with IMN who were GAg-, while the CI value was higher in patients with IMN who were GAg+. Patients with IMN who were GAg + were divided into the SAb+/GAg + group and the SAb-/GAg + group. Patients with IMN who were SAb+/GAg + had higher Fib and MA values than patients with IMN who were SAb-/GAg+. Correlation analysis showed that serum anti-PLA2R antibodies were positively correlated with fibrinogen, D-dimer, K time, CI value, α-angle, and MA value. Multiple linear regression analysis indicated that anti-PLA2R antibodies were independently correlated with fibrinogen and MA value. CONCLUSION: Our study provides a new perspective on the underlying mechanisms of hypercoagulability in patients with IMN. Anti-PLA2R antibodies are associated with hypercoagulability in patients with IMN and may affect coagulation in patients with IMN by affecting platelet aggregation function and fibrinogen counts.
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Autoanticorpos , Glomerulonefrite Membranosa , Receptores da Fosfolipase A2 , Trombofilia , Humanos , Receptores da Fosfolipase A2/imunologia , Glomerulonefrite Membranosa/sangue , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/complicações , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Trombofilia/etiologia , Trombofilia/imunologia , Trombofilia/sangue , Autoanticorpos/sangueRESUMO
OBJECTIVE: To demonstrate hypercoagulability with a benchtop viscoelastic monitor in cats with congestive heart failure (CHF) and/or aortic thromboembolism (ATE) compared to controls. METHODS: 97 cats were enrolled throughout this prospective observational cohort study from September 2022 through October 2023. Cats were grouped by diagnosis of CHF, ATE, ATE plus CHF, or controls. Enrollment required diagnosis of heart disease and no previous antithrombotic therapy. The results of viscoelastic testing with the benchtop viscoelastic coagulation monitor (VCM Vet [VCM]; Entegrion) were compared between groups using factorial analysis of variance. RESULTS: Cats with heart disease had significantly higher clot times when compared to controls (control: mean, 285.3 [SD, 172.6]; CHF: mean, 391.7 [SD, 106.8]; ATE: mean, 415.9 [SD, 109.2]; and ATE plus CHF: mean, 368.6 [SD, 232.6]). Heart disease cats were noted to have significantly lower 45-minute lysis index values (control: median, 100 [range, 93 to 100]; CHF: median, 99 [range, 89 to 100]; ATE: median, 98 [range, 88 to 100]; and ATE plus CHF: range, 98 [91 to 100]). Age was a covariate to this variable, and when applied to analysis, statistical significance was lost. No significant difference in any other variables were noted. CLINICAL RELEVANCE: The hypercoagulability of ATE and CHF cats was not detected by the VCM. Further research with other coagulation monitors is required in this population.
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Doenças do Gato , Insuficiência Cardíaca , Tromboembolia , Trombofilia , Animais , Gatos , Doenças do Gato/sangue , Insuficiência Cardíaca/veterinária , Insuficiência Cardíaca/sangue , Trombofilia/veterinária , Trombofilia/sangue , Masculino , Feminino , Estudos Prospectivos , Tromboembolia/veterinária , Tromboembolia/sangue , Doenças da Aorta/veterinária , Doenças da Aorta/sangue , Estudos de CoortesRESUMO
ß-Thalassemia especially transfusion-dependent thalassemia (TDT) associates with a hypercoagulable state, which is the main cause of thromboembolic events (TEE). Plasma viscosity and rheological parameters could be essential markers for determining hypercoagulable state in ß-thalassemia patients. The traditional methods for measuring viscosity are often limited by large sample volumes and are impractical for routine clinical monitoring. The compact differential dynamic microscopy-based device (cDDM), an optical microscopy for quantitative rheological assessment, was developed and applied for prognosis of the hypercoagulable state in ß-TDT with and without splenectomy. The device was performed plasma viscosity measurement using low plasma volume (8 µL) and revealed a value as modulus of complex viscosity |η(ω)| in 7 min. We also parallelly demonstrated the correlation of the viscosity and related-coagulable parameters: complete blood count, prothrombin time (PT), activated partial thromboplastin time (APTT), protein C (PC), protein S (PS), CD62P and CD63 expression, and platelet aggregation test. The thalassemia plasma exhibited a higher value of |η(ω)| than healthy plasma, which can represent a different viscoelastic property among the groups. Even all related-coagulable parameters indicated hypercoagulable state in both nonsplenectomies and splenectomies ß-TDT patients when compared to control, only high platelet numbers significantly correlated to high plasma viscosity in the splenectomy group. However, the other coagulable parameters have shown a trend of positive relationship with high plasma viscosity in all ß-1thalassemia TDT patients. The relative results suggested that our device would be an approach tool for early detection of hypercoagulable state in transfusion-dependent-ß-thalassemia patients, which can help to prevent TEE and the critical consequent-complications.
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Teste de Materiais , Trombofilia , Talassemia beta , Humanos , Talassemia beta/sangue , Talassemia beta/complicações , Trombofilia/sangue , Trombofilia/diagnóstico , Transfusão de Sangue , Microscopia , Materiais Biocompatíveis/química , Viscosidade Sanguínea , Masculino , Tamanho da Partícula , Diagnóstico Precoce , FemininoRESUMO
BACKGROUND AND OBJECTIVES: Obesity is hypothesized to induce a hypercoagulable state that increases stroke risk. The molecular mechanisms underlying this association are largely uncharacterized. We aimed to apply mendelian randomization to identify whether the association of genetically proxied body mass index (BMI) with cardioembolic stroke risk is mediated by changes in levels of circulating coagulation factors. METHODS: Genetic proxies for BMI and levels of circulating coagulation factors were obtained, respectively, from the Genetic Investigation of ANthropometric Traits consortium (n = 694,649) and deCODE cohort (n = 35,559). Genetic associations with cardioembolic stroke risk were obtained from the GIGASTROKE consortium (10,804 cases and 1,234,804 controls). We performed a two-sample mendelian randomization analysis testing the association of genetically proxied BMI with cardioembolic stroke risk, genetically proxied BMI with levels of coagulation factors, and genetically proxied levels of coagulation factors with cardioembolic stroke risk. These estimates were carried forward to mediation and sensitivity analyses. RESULTS: A 1-SD increase in genetically proxied BMI associated with increased cardioembolic stroke risk (OR of cardioembolic stroke per 1-SD of BMI 1.20, 95% CI 1.08-1.33, p = 8.65 × 10-4) with similar findings in statistical sensitivity analyses more robust to the inclusion of pleiotropic variants. Genetically proxied BMI was further associated with increased levels of Factor VII, Factor Xa, Factor XI, and Protein S (all p < 5.9 × 10-6). Of these factors, genetically proxied levels of Factor XI were associated with cardioembolic stroke risk (OR of cardioembolic stroke per 1-SD increase in Factor XI levels 1.32, 1.19-1.46, p = 6.18 × 10-8). The mediated effect of genetically proxied BMI through Factor XI accounted for 26% (6%-49%) of the total effect of BMI on cardioembolic stroke. DISCUSSION: Human genetic data support increased levels of Factor XI as a mechanistic explanation for how obesity increases cardioembolic stroke risk. The clinical relevance of this association warrants further investigation within ongoing clinical trials of Factor XI inhibition.
Assuntos
Índice de Massa Corporal , Análise da Randomização Mendeliana , Obesidade , Trombofilia , Humanos , Obesidade/genética , Obesidade/complicações , Obesidade/sangue , Obesidade/epidemiologia , Trombofilia/genética , Trombofilia/sangue , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/sangue , Feminino , Fatores de Coagulação Sanguínea/genética , Masculino , Fatores de Risco , AVC Embólico/genética , AVC Embólico/epidemiologiaRESUMO
Venous thromboembolism, which is common in cancer patients and accompanies or even precedes malignant tumors, is known as cancer-related thrombosis and is an important cause of cancer- associated death. At present, the exact etiology of the elevated incidence of venous thrombosis in cancer patients remains elusive. Platelets play a crucial role in blood coagulation, which is intimately linked to the development of arterial thrombosis. Additionally, platelets contribute to tumor progression and facilitate immune evasion by tumors. Tumor cells can interact with the coagulation system through various mechanisms, such as producing hemostatic proteins, activating platelets, and directly adhering to normal cells. The relationship between platelets and malignant tumors is also significant. In this review article, we will explore these connections.
Assuntos
Plaquetas , Progressão da Doença , Neoplasias , Trombofilia , Humanos , Plaquetas/metabolismo , Plaquetas/patologia , Neoplasias/sangue , Neoplasias/patologia , Neoplasias/complicações , Trombofilia/sangue , Trombofilia/etiologia , Coagulação Sanguínea/fisiologiaRESUMO
Patients diagnosed with lymphoma or multiple myeloma are at elevated risk of venous thromboembolism (VTE). Optimum risk stratification and effective thromboprophylaxis can only be achieved through the development of a multiple-specific risk score that successfully captures all aspects of the heterogeneous prothrombotic environment existing in these patients. Our aim was to identify risk factors for thrombosis and suggest an improved tool combining clinical data, thrombo-inflammatory biomarkers and genetic (Thrombo inCode® test) variables for predicting thrombotic risk in patients with lymphoma and multiple myeloma. A prospective longitudinal study was conducted on newly-diagnosed lymphoma and multiple myeloma patients who presented at our institution between February 2020 and January 2021. The study included 47 patients with lymphoma and 16 patients with multiple myeloma. We performed a follow-up of 1 year or until September 2021. The incidence of venous thrombosis and associated risk factors were analysed, including the genetic Thrombo inCode® test. Khorana and ThroLy scores for lymphoma patients and IMPEDE VTE score for myeloma patients were calculated. At a median follow-up of 9.1 months, VTE incidence was 9.5% (6/63), with 4 and 2 patients with lymphoma and myeloma who developed the events, respectively. Univariate analysis showed that the incidence of thrombosis was significantly higher in patients with ECOG ≥ 2 and prior immobility. Median factor VIII levels were significantly higher in patients with thrombosis (with increased values in all of them). Moreover, there was a trend in genetic variant rs5985 (factor XIII) as a protective factor, and a trend to higher thrombotic risk in patients with factor V Leiden, rs2232698 variant (serpinA10), low total protein S activity, elevated D-dimer, aggressive lymphoma and treatment with dexamethasone. The results of our study demonstrate promise for the potential use of widely accessible markers to increase precision in risk prediction for VTE in patients with lymphoma and multiple myeloma, particularly ECOG ≥ 2, immobility and higher factor VIII levels, as well as lymphoma aggressiveness, treatment with dexamethasone and the haemostatic biomarkers D-dimer and total protein S activity. Additionally, genetic variants factor V Leiden, serpinA10 rs2232698 and factor XIII-A Val34Leu warrant further investigation for use in the research setting.
Assuntos
Linfoma , Mieloma Múltiplo , Trombofilia , Humanos , Mieloma Múltiplo/genética , Mieloma Múltiplo/sangue , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Linfoma/genética , Linfoma/sangue , Linfoma/complicações , Linfoma/diagnóstico , Estudos Prospectivos , Trombofilia/genética , Trombofilia/sangue , Trombofilia/diagnóstico , Trombofilia/complicações , Fatores de Risco , Adulto , Estudos Longitudinais , Incidência , Tromboembolia Venosa/genética , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/diagnóstico , Medição de Risco/métodos , Biomarcadores/sangue , Trombose/genética , Trombose/etiologia , Trombose/sangue , Trombose/diagnósticoRESUMO
INTRODUCTION: Traditionally and empirically, Hibiscus sabdariffa L. has been used in treating diabetes mellitus due to its antioxidant activity. This study aimed to investigate the effect of administering the ethyl acetate fraction of hibiscus calyxes (EAFHCs) on malondialdehyde (MDA) levels, tumor necrosis factor-α (TNF-α) levels, bleeding time, and platelet count in male white rats induced with streptozotocin-induced diabetes. METHOD: Thirty-six Wistar Kyoto rats were induced with intraperitoneal streptozotocin at 55 mg/kg BW and stabilized for 5 days to obtain diabetic conditions. Diabetic animals were divided into four groups; the diabetic group was given vehicle, the glibenclamide group was given 0.45 mg/kg BW of glibenclamide, and two groups were administered the EAFHCs at doses of 100 mg/kg BW and 200 mg/kg BW for 5 days. Subsequently, the MDA, TNF-α, bleeding time and platelet count levels were examined on days 1, 3, and 5, respectively. All data were analyzed using two-way ANOVA followed by the Duncan Multiple Range Test (DMRT). RESULTS: EAFHC significantly reduced MDA and TNF-α levels (p < 0.05). Additionally, this fraction appeared to shorten bleeding time and decrease platelet count in diabetic rats. Administration of the EAFHC for 5 days effectively lowered MDA and TNF-α levels significantly, decreased platelet counts and prolonged coagulation (p < 0.05) in diabetic rats. CONCLUSION: This study demonstrates that EAFHC effectively reduces MDA and TNF-α levels and reduces the risk of hypercoagulability in diabetic model.
Assuntos
Diabetes Mellitus Experimental , Hibiscus , Malondialdeído , Extratos Vegetais , Fator de Necrose Tumoral alfa , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/complicações , Masculino , Hibiscus/química , Fator de Necrose Tumoral alfa/sangue , Malondialdeído/sangue , Malondialdeído/metabolismo , Ratos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/administração & dosagem , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Trombofilia/sangue , Ratos Endogâmicos WKY , Acetatos , Contagem de Plaquetas , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Estreptozocina , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Tempo de SangramentoRESUMO
Adults with sickle cell trait (SCT) have a procoagulant state with increased risk of thromboembolism, but limited data are available for children. We compared the coagulation profile of children with SCT, different sickle cell disease (SCD) genotypes, and healthy controls. Compared to controls and similarly to HbSC patients, 41 SCT children (mean age 6.85 years; 20 males; 88% Africans) had a characteristic procoagulant profile: higher levels of factor VIII, von Willebrand factor (VWF) Ag and CBA, D-dimer; lower levels of ADAMTS 13 activity, ADAMTS13 activity: VWFAg, plasminogen activator inhibitor, tissue plasminogen activator. Moreover, 13/41 had clinical complications of SCD, five requiring hospitalization.
Assuntos
Traço Falciforme , Trombofilia , Humanos , Traço Falciforme/complicações , Traço Falciforme/sangue , Masculino , Feminino , Criança , Trombofilia/etiologia , Trombofilia/sangue , Pré-Escolar , Adolescente , Lactente , Estudos de Coortes , Fator de von Willebrand/análise , Fator de von Willebrand/metabolismoRESUMO
BACKGROUND: This study aimed compare efficacy of edoxaban and enoxaparin upon biomarkers of hypercoagulability in patients with cancer-related embolic stroke of undetermined source (ESUS). METHODS: In this open-label, randomized, pilot trial, patients with cancer-related ESUS within 30 days of diagnosis were randomly assigned (1:1) to receive edoxaban (60 mg once daily) or enoxaparin (1 mg/kg twice daily) for 90 days. The primary endpoint was interval change of serum D-dimer level between days 0 and 7. The secondary endpoints were microembolic signals detected by transcranial Doppler at 7 and 90 days, the modified Rankin scale score, and stroke recurrence during 90 days. Safety outcomes included major bleeding and all-cause death at 90 days. RESULTS: Of 303 patients with ischemic stroke and cancer, 40 fully met enrollment criteria and were randomized. Baseline D-dimer levels were numerically higher in the edoxaban group (22.9 ± 15.9 µg/mL vs 16.9 ± 16.9 µg/mL). D-dimer level change (%) between days 0 and 7 was similar in the two groups (53.2 ± 25.7 vs 52.2 ± 52.0; P = 0.11). Microembolic signals were detected in 41.1% and 43.8% at baseline, 41.2% and 42.9% at day 7, and 25.0% and 28.6% at day 90 in the edoxaban and enoxaparin groups, respectively. Non-significantly higher major bleeding (35.0% vs 10.0%, P = 0.06) and 90-day mortality (40.0% vs 25.0%, P = 0.31) were noted in the edoxaban group. CONCLUSION: Edoxaban and enoxaparin were comparable with respect to the biomarkers of hypercoagulability and cerebral thromboembolism. Larger trials are warranted to compare effects of edoxaban and enoxaparin upon recurrent stroke and major bleeding in patients with cancer-related ESUS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03570281 (https://clinicaltrials.gov/ct2/show/NCT03570281).
Assuntos
Biomarcadores , Enoxaparina , Inibidores do Fator Xa , Produtos de Degradação da Fibrina e do Fibrinogênio , Neoplasias , Piridinas , Tiazóis , Trombofilia , Humanos , Feminino , Masculino , Piridinas/uso terapêutico , Tiazóis/uso terapêutico , Idoso , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/sangue , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Trombofilia/sangue , Pessoa de Meia-Idade , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Inibidores do Fator Xa/uso terapêutico , Enoxaparina/uso terapêutico , Biomarcadores/sangue , Projetos Piloto , Anticoagulantes/uso terapêutico , Resultado do TratamentoRESUMO
Chronic mountain sickness is a maladaptive syndrome that affects individuals living permanently at high altitude and is characterized primarily by excessive erythrocytosis (EE). Recent results concerning the impact of EE in Andean highlanders on clotting and the possible promotion of hypercoagulability, which can lead to thrombosis, were contradictory. We assessed the coagulation profiles of Andeans highlanders with and without excessive erythrocytosis (EE+ and EE-). Blood samples were collected from 30 EE+ and 15 EE- in La Rinconada (Peru, 5100-5300 m a.s.l.), with special attention given to the sampling pre-analytical variables. Rotational thromboelastometry tests were performed at both native and normalized (40%) haematocrit using autologous platelet-poor plasma. Thrombin generation, dosages of clotting factors and inhibitors were measured in plasma samples. Data were compared between groups and with measurements performed at native haematocrit in 10 lowlanders (LL) at sea level. At native haematocrit, in all rotational thromboelastometry assays, EE+ exhibited hypocoagulable profiles (prolonged clotting time and weaker clot strength) compared with EE- and LL (all P < 0.01). At normalized haematocrit, clotting times were normalized in most individuals. Conversely, maximal clot firmness was normalized only in FIBTEM and not in EXTEM/INTEM assays, suggesting abnormal platelet activity. Thrombin generation, levels of plasma clotting factors and inhibitors, and standard coagulation assays were mostly normal in all groups. No highlanders reported a history of venous thromboembolism based on the dedicated survey. Collectively, these results indicate that EE+ do not present a hypercoagulable profile potentially favouring thrombosis.