RESUMO
PURPOSE: Hyperglycemia is one of the factors responsible for the molecular alterations that modify hemostasis. The aim of this study was to determine the levels of circulating molecules that have a prothrombotic impact on the child and adolescent population with type 1 diabetes mellitus. METHODS: There were 35 patients with type 1 diabetes mellitus (11.0±2.5 years of age and a median 3.7±2.0 years of the disease) with no vascular complications and 20 healthy controls with similar age, sex, and body mass index included in the study. The evaluated parameters were fibrinogen, plasminogen activator inhibitor-1 (PAI1), von Willebrand factor antigen, and standard coagulation tests (platelet count, prothrombin time, and activated partial thromboplastin time). Glycemic control was evaluated by hemoglobin A1c and fasting blood glucose tests, and the presence of retinopathy and nephropathy was ruled out. The data obtained were analyzed by IBM SPSS Statistics ver. 20.0 and expressed as mean±standard deviation. The Pearson correlation coefficient was applied to investigate correlations between variables. RESULTS: Diabetic patients showed significantly higher levels of fibrinogen (308±66 mg/dL vs. 246±18 mg/dL, P=0.0001), PAI-1 (41.6±12 ng/mL vs. 11.7±1.0 ng/mL, P=0.0001), and von Willebrand factor antigen (284%±55% vs. 121%±19%, P=0.0001). However, standard coagulation tests did not show differences between the 2 groups. PAI-1 was correlated with glycemia, hemoglobin A1c, fibrinogen, and von Willebrand factor antigen. CONCLUSION: Elevated levels of fibrinogen, PAI-1, and von Willebrand factor antigen were found in the pediatric and adolescent population with type 1 diabetes mellitus, which suggests a prothrombotic state.
RESUMO
The outbreak of coronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). COVID-19 and type 2 diabetes (T2D) have now merged into an ongoing global syndemic that is threatening the lives of millions of people around the globe. For this reason, there is a deep need to understand the immunometabolic bases of the main etiological factors of T2D that affect the severity of COVID-19. Here, we discuss how hyperglycemia contributes to the cytokine storm commonly associated with COVID-19 by stimulating monocytes and macrophages to produce interleukin IL-1ß, IL-6, and TNF-α in the airway epithelium. The main mechanisms through which hyperglycemia promotes reactive oxygen species release, inhibition of T cell activation, and neutrophil extracellular traps in the lungs of patients with severe SARS-CoV-2 infection are also studied. We further examine the molecular mechanisms by which proinflammatory cytokines induce insulin resistance, and their deleterious effects on pancreatic ß-cell exhaustion in T2D patients critically ill with COVID-19. We address the effect of excess glucose on advanced glycation end product (AGE) formation and the role of AGEs in perpetuating pneumonia and acute respiratory distress syndrome. Finally, we discuss the contribution of preexisting endothelial dysfunction secondary to diabetes in the development of neutrophil trafficking, vascular leaking, and thrombotic events in patients with severe SARS-CoV-2 infection. As we outline here, T2D acts in synergy with SARS-CoV-2 infection to increase the progression, severity, and mortality of COVID-19. We think a better understanding of the T2D-related immunometabolic factors that contribute to exacerbate the severity of COVID-19 will improve our ability to identify patients with high mortality risk and prevent adverse outcomes.
RESUMO
Resumen: Las pérdidas de embarazos son una complicación obstétrica frecuente. Se conoce que, 15% de las mujeres embarazadas tienen al menos una pérdida esporádica. El 5% experimentan 2 pérdidas, y hasta un 1% 3 o más. La edad materna avanzada, la multiparidad y el antecedente de pérdida de embarazo previo aumentan el riesgo. La vinculación de los estados protrombóticos, hereditarios y adquiridos, con las pérdidas de embarazo se relaciona con el hecho de que para que se mantenga el embarazo es necesario exista una adecuada circulación placentaria. A lo largo de los años se ha estudiado la relación que existe entre los diferentes estados protrombóticos hereditarios y adquiridos con estas complicaciones vasculares que determinan pérdidas de embarazo y complicaciones obstétricas. Se realiza una revisión sobre las trombofilias hereditarias y adquiridas con ésta entidad.
Abstract: Pregnancy losses are a common obstetric complication. It is known that 15% of pregnant women have at least one sporadic loss. 5% experience 2 losses, and up to 1% 3 or more. Advanced maternal age, multiparity, and a history of prior pregnancy loss increase the risk. The link between hereditary and acquired prothrombotic states with pregnancy losses is related to the fact that adequate placental circulation is necessary for the pregnancy to be maintained. Over the years, the relationship between the different hereditary and acquired prothrombotic states with these vascular complications that lead to pregnancy losses and obstetric complications has been studied. A review is carried out on the hereditary and acquired thrombophilias with this entity.
Resumo: A perda da gravidez é uma complicação obstétrica comum. Sabe-se que 15% das gestantes apresentam pelo menos uma perda esporádica. 5% experimentam 2 perdas e até 1% 3 ou mais. Idade materna avançada, multiparidade e história de perda de gravidez anterior aumentam o risco. A ligação entre os estados protrombóticos hereditários e adquiridos com as perdas gestacionais está relacionada ao fato de que a circulação placentária adequada é necessária para a manutenção da gravidez. Ao longo dos anos, estudou-se a relação entre os diferentes estados pró-trombóticos hereditários e adquiridos com essas complicações vasculares que levam à perda da gravidez e complicações obstétricas. É realizada uma revisão das trombofilias hereditárias e adquiridas com essa entidade.
RESUMO
La respuesta a la infección viral produce un estado de trombosis o hipercoagulabilidad que, unido a la inflamación de las células endoteliales, puede generar disfunción plaquetaria y predisposición a la formación de trombos que, aunque con frecuencia son más venosos, también pueden aparecer en el sistema arterial y producir infartos a cualquier nivel así como tromboembolia e hipertensión pulmonar. Estas manifestaciones han sido captadas hospitalariamente y al egreso de los pacientes detectados por SARS-CoV-2 habiendo ya cumplido el tiempo establecido de virulencia. Los criterios diagnósticos de respuesta inmunológica trombótica asociada a COVID-19 (RITAC) ayudan a seleccionar al paciente que está predispuesto a esta condición; a esto se añade que el paciente ya tiene un diagnóstico de infección por SARS-CoV-2 (AU)
The response to viral infection produces a prothrombotic state of hypercoagulability , united with an inflammation of endothelial cells, It can generate platelet dysfunction and predisposition to the formation of thrombus, that, although, are more frequently venous, Also, it can appear in the arterial system and cause heart attacks at any level; thromboembolism and pulmonary hypertension, as well. These manifestations have been captured hospitably and with the egress of patients detected by SARS-CoV-2. The diagnostic criteria of RITAC (abbreviation in Spanish of Thrombotic Immune Response Associated to COVID-19), help to select the patient who is predisposed to this condition; adding that the patient already has a diagnosis of SARS-CoV-2 infection (AU)
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Pneumonia Viral , Trombose , Infecções por Coronavirus , Betacoronavirus , Panamá , Embolia Pulmonar , Unidade Hospitalar de Odontologia/estatística & dados numéricosRESUMO
Neoplasms exhibits a high incidence and mortality rates due to their complex and commonly overlapping clinical, biochemical, and morphologic profiles influenced by acquired or inherited molecular abnormalities, cell of origin, and level of differentiation. Obesity appears related to ~20% of cancers including endometrial, esophageal, colorectal, postmenopausal breast, prostate, and renal. Several factors other than obesity, i.e., insulin, insulin-like growth factor, sexual hormones, and adipokines may play a potential role in neoplasia. Cancer-associated hypercoagulable and thrombotic states are influenced by abnormalities in the vascular wall and susceptibility to invasion, interference in blood flow and increase in circulating tissue factor and thrombin, activation of cell growth factors, the presence of a central catheter, chemotherapies, neoplasm type, and surgery. In cancer, thromboembolic complications are the second most frequent cause of death with pulmonary thromboembolism in ~50% of cases postmortem. Thrombosis worsens prognosis as demonstrated with a survival rate as low as 12% per year vs 36% in nonthrombic patients. Deep vein thrombosis is the most frequent thromboembolic complication in cancer. It is usually detected at diagnosis and within the first 3 months of chemotherapy. The underlining mechanisms of this association should be further studied to identify patients at higher risk and develop adequate prevention, diagnostic, and treatment measures. The D-dimer test can be successfully used to assess the fibrinolytic phase of coagulation and as such is routinely used in suspected cases of deep vein thrombosis and pulmonary thromboembolism. In addition, significant advances have been made in understanding the composition and functional capabilities of the gut microbiota in the inflammatory process, obesity, and its roles in cancer; however, the intricate balance that exists within the microbiota may not only affect the host directly, it can also disrupt the entire microbial community. CONCLUSIONS: Cancer is a prothrombotic and inflammatory state in which the activation of coagulation is related to tumor growth, angiogenesis, and metastasis. It is important to identify the relationship between body mass index with these processes and clarify their importance in cancer prognosis. Future research should answer the question if manipulation of resident microbial communities could potentially improve prognosis and treatment outcome.
Assuntos
Inflamação/complicações , Neoplasias/complicações , Obesidade/complicações , Trombose/complicações , Adipócitos/patologia , Animais , Citocinas/análise , Humanos , Inflamação/patologia , Inflamação/fisiopatologia , Macrófagos/patologia , Neoplasias/patologia , Neoplasias/fisiopatologia , Obesidade/patologia , Obesidade/fisiopatologia , Trombose/patologia , Trombose/fisiopatologiaRESUMO
Objetivo: Este estudio fue diseñado para explorar la presencia de un estado protrombótico, disfunción fibrinolítica e inflamación en sujetos con intolerancia a la glucosa, mediante la evaluación de los marcadores séricos de trombosis, fibrinólisis e inflamación. Métodos: Se estudiaron 48 individuos consecutivos, 25 intolerantes a la glucosa: (nueve hombres y 16 mujeres, 50.0 ±9.2 años) y 23 sujetos control (seis hombres y 17 mujeres, 48.0 ±11 años). Se compararon entre ambos grupos los niveles de dímero-D y fibrinógeno como marcadores de trombosis, el PAI-1 como marcador de fibrinólisis y la proteína C reactiva ultrasensible (PCR-us) como marcador de inflamación. Resultados: En los sujetos intolerantes a la glucosa respecto al grupo control, se observaron diferencias significativas en los marcadores de trombosis: fibrinógeno 317.7 ± 32.1 vs. 266.7 ± 25.4 mg/dL (p<0.0001), dímero-D 489.6 ± 277.3 vs. 345.8 ± 158.9 ng/mL (p<0.01) y en el marcador de fibrinólisis PAI-1 66.4 ± 30.7 vs. 35.5 ± 31.0 ng/mL (p<0.006). En el marcador de inflamación, PCR-us no se observó diferencia significativa, respecto al grupo control 0.45 ± 0.6 vs. 0.38 ± 0.4 mg/dL (p<0.28). Conclusiones: Estos resultados sugieren la presencia de un estado protrombótico con disfunción del sistema fibrinolítico, en sujetos intolerantes a la glucosa.
Objective: This study was designed to explore the presence of a prothrombotic state, fibrinolytic dysfunction and infammation in impaired glucose tolerance subjects, by evaluating serum markers of thrombosis, fibrinolysis and infammation. Methods: In 48 consecutive adults, 25 patients with impaired glucose tolerance (nine men and 16 women, 50.0 ±9.2 years) were compared with 23 control subjects (six men and 17 women, 48.0 ±11 years). The markers of thrombotic activation used were D-dimer and fibrinogen. Fibrinolysis dysfuntion was evaluated with plasminogen activator inhibitor 1 (PAI-1) and the infammatory marker studied was hs-C reactive protein (hs-CRP). Results: The markers of thrombotic state were significantly higher in patients with impaired glucose tolerance (IGT) than in controls: D dimer (489.6 ± 277.3 vs. 345.8 ± 158.9 ng/mL) (p < 0.01) and fibrinogen (317.7 ±32.1 vs. 266.7 ±25.4 mg/dL) (p < 0.0001). Fibrinolytic marker PAI-1 also differed significantly between the two study groups (66.4 ± 30.7 vs. 35.5 ± 31.0 ng/ mL) (p < 0.006). However, hs-CRP, as infammation marker, (0.45 ± 0.62 mg/dL vs. 0.38 ± 0.47) did not differ significantly between the two study groups (<0.28). Conclusion: This result suggests the presence of a prothrombotic state with fibrinolytic dysfunction in subjects with impaired glucose tolerance.