Patients hospitalized with active tuberculosis and Covid-19 coinfection: A matched case-control from the Brazilian Covid-19 Registry.

Although control of Covid-19 has improved, the virus continues to cause infections, such as tuberculosis, that is still endemic in many countries, representing a scenario of coinfection. To compare Covid-19 clinical manifestations and outcomes between patients with active tuberculosis infection and matched controls. This is a matched case-control study based on data from the Brazilian Covid-19 Registry, in hospitalized patients aged 18 or over with laboratory confirmed Covid-19 from March 1, 2020, to March 31, 2022. Cases were patients with tuberculosis and controls were Covid-19 patients without tuberculosis. From 13,636 Covid-19, 36 also had active tuberculosis (0.0026%). Pulmonary fibrosis (5.6% vs 0.0%), illicit drug abuse (30.6% vs 3.0%), alcoholism (33.3% vs 11.9%) and smoking (50.0% vs 9.7%) were more common among patients with tuberculosis. They also had a higher frequency of nausea and vomiting (25.0% vs 10.4%). There were no significant differences in in-hospital mortality, mechanical ventilation, need for dialysis and ICU stay. Patients with TB infection presented a higher frequency of pulmonary fibrosis, abuse of illicit drugs, alcoholism, current smoking, symptoms of nausea and vomiting. The outcomes were similar between them.

Interference of medicines in laboratory exams / Interferência dos medicamentos nos exames laboratoriais

ABSTRACT Objective: Conduct a survey on the interference of drugs in laboratory tests. Methodology: To identify the interference of each medication in laboratory tests, the Municipal List of Essential Medicines (Remume) of a medium-sized municipality in the state of Minas Gerais was used along with the following sources of information: Dynamed, Micromedex® and Nursing Reference Center. Results: We observed that the majority (67.7%) of Remume drugs can interfere in one or more laboratory tests; among them, the main classes of drugs are diuretics, beta blockers, ß-lactams, sulfonamides, macrolides, tricyclic antidepressants and selective serotonin reuptake inhibitors antidepressants. Conclusion: It is extremely important to disseminate knowledge about these interferences so that health professionals are alert and know how to identify the possible changes, reducing analytical errors and subsequently misdiagnosis and erroneous monitoring. Continued education on drug interference in laboratory tests is equally important.

RESUMEN Objetivo: Llevar a cabo una encuesta acerca de la interferencia de los medicamentos en las pruebas de laboratorio. Métodos: Usamos la Relación Municipal de Medicamentos Esenciales (Remume) de una municipalidad mediana en el estado de Minas Gerais y las siguientes fuentes de información: Dynamed, Micromedex® y Nursing Reference Center. Resultados: Observamos que la mayor parte (67,7%) de los medicamentos de Remume puede interferir en una o más pruebas de laboratorio; entre ellos, las principales clases son los diuréticos, beta bloqueadores, betalactámicos, sulfonamidas, macrólidos, antidepresivos tricíclicos y antidepresivos inhibidores selectivos de la recaptación de serotonina. Conclusión: Es muy importante divulgar el conocimiento respecto a esas interferencias para que los profesionales de la salud puedan identificar las posibles alteraciones en las pruebas, reduciendo errores analíticos y diagnósticos y monitoreos equivocados. Por lo tanto, es necesaria una educación continuada acerca de las interferencias de medicamentos en las pruebas de laboratorio.

RESUMO Objetivo: Realizar um levantamento sobre a interferência dos medicamentos nos exames laboratoriais. Métodos: Utilizamos a Relação Municipal dos Medicamentos Essenciais (Remune) de um município de médio porte do estado de Minas Gerais e as seguintes fontes de informações: Dynamed, Micromedex® e Nursing Reference Center. Resultados: Observamos que a maioria (67,7%) dos medicamentos da Remune pode interferir em um ou mais exames laboratoriais; entre eles, as principais classes de medicamentos são os diuréticos, betabloqueadores, betalactâmicos, sulfonamidas, macrolídeos, antidepressivos tricíclicos e antidepressivos inibidores seletivos da recaptação de serotonina. Conclusão: É muito importante divulgar o conhecimento a respeito dessas interferências para que os profissionais da área da saúde possam identificar as possíveis alterações nos exames, reduzindo erros analíticos e diagnósticos e monitoramentos equivocados. Portanto, faz-se necessária a educação continuada sobre as interferências de medicamentos nos exames laboratoriais.

Sickle cell disease: Hemostatic and inflammatory changes, and their interrelation.

Sickle cell disease, the most common genetic blood disorder in the world, has high clinical variability, negatively impacts quality of life and contributes to early mortality. Sickled erythrocytes cause blood flow obstruction, hemolysis, and several hemostatic changes that promote coagulation. These events, in turn, induce chronic inflammation, characterized by elevated plasma levels of pro-inflammatory markers, which aggravates the already unfavorable state of the circulatory system. Empirical evidence indicates that the hemostatic and inflammatory systems continuously interact with each other and thereby further propagate the hypercoagulability and inflammatory conditions. In this review article, we discuss the pathophysiological aspects of sickle cell disease and the hemostatic and inflammatory changes that underlie its pathogenesis.

Apolipoprotein E and PAI-1 gene polymorphisms and no association with arterial ischemic stroke and peripheral arterial disease manifestations / Polimorfismos nos genes da apolipoproteína E e do PAI-1 e não associação com as manifestações de acidente vascular cerebral e doença arterial periférica

ABSTRACT Introduction: Arterial thrombosis is considered a multifactorial disease, resulting from the interaction of genetic and acquired risk factors. Objectives: The aim of this study was to investigate the presence of the polymorphism in inhibitor of plasminogen activator type 1 (PAI-1) and apolipoprotein E (ApoE) genes and its interactions with PAI-1 levels and lipids and apolipoprotein profiles, respectively, as well as the frequencies of these polymorphisms and their association with thrombosis. Methods: Ninety-seven patients [48 with arterial ischemic stroke (IS) and 49 with peripheral arterial disease (PAD)], treated at the hematology medical service were included in this study. Polymorphisms were also investigated in 201 control subjects. Polymorphisms were investigated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: For the PAI-1 polymorphism, there were 54.2% heterozygous (HT) genotypes and 12.5% homozygous (HM) genotypes in the patients' group, and 52.7% HT genotypes and 21.3% HM genotypes in the controls. For the ApoE polymorphism, there were 56.3% (ε3ε3), 6.3% (ε4ε4), 8.3% (ε2ε3), 4.2% (ε2ε4) and 24.9% (ε3ε4) in the patients, and 61.2% (ε3ε3), 4.5% (ε4ε4), 8% (ε2ε3), 4.5% (ε2ε4) and 21.8% (ε3ε4) in the controls. Conclusion: No significant difference was observed by comparing patients and controls. In this study, no association was found between the presence of the evaluated polymorphisms and the occurrence of thrombotic events.

RESUMO Introdução: A trombose arterial é considerada uma doença multifatorial, resultante da interação de fatores de risco genéticos e adquiridos. Objetivos: O objetivo deste estudo foi investigar a presença dos polimorfismos nos genes do inibidor da ativação do plasminogênio tipo 1 (PAI-1) e da apolipoproteína E (ApoE), bem como suas interações com níveis de PAI-1 e lipídios e perfis de apolipoproteína, respectivamente, além das frequências desses polimorfismos e sua associação com trombose. Métodos: Noventa e sete pacientes [48 com acidente vascular cerebral isquêmico arterial (AVC) e 49 com doença arterial periférica (DAP)], tratados no serviço médico de hematologia, foram incluídos neste estudo. Os polimorfismos também foram investigados em 201 indivíduos-controle. Os polimorfismos foram investigados por reação em cadeia da polimerase-fragmento de restrição polimorfismo (PCR-RFLP). Resultados: Para o polimorfismo PAI-1, havia 54,2% genótipos heterozigotos (HT) e 12,5% genótipos de homozigoto (HM) no grupo dos pacientes, e 52,7% genótipos HT e 21,3% genótipos HM nos grupos-controle. Para o polimorfismo da ApoE, havia 56,3% (ε3ε3), 6,3% (ε4ε4), 8,3% (ε2ε3), 4,2% (ε2ε4) e 24,9% (ε3ε4) nos pacientes, e 61,2% (ε3ε3), 4,5% (ε4ε4), 8% (ε2ε3), 4,5% (ε2ε4) e 21,8% (ε3ε4) nos controles. Conclusão: Nenhuma diferença significativa foi observada comparando pacientes e controles. Neste estudo, não foi encontrada associação entre a presença dos polimorfismos avaliados e a ocorrência de eventos trombóticos.

Relationship between ABO blood groups and von Willebrand factor, ADAMTS13 and factor VIII in patients undergoing hemodialysis.

Several studies have demonstrated that non-O blood groups subjects present an increased VTE risk as compared to those carrying O blood group. The aim of this study was to investigate the ABO blood groups influence on factor VIII (FVIII) activity, von Willebrand factor (VWF), and ADAMTS13 plasma levels in patients undergoing hemodialysis (HD). Patients undergoing HD (N=195) and 80 healthy subjects (control group) were eligible for this cross-sectional study. The ABO blood group phenotyping was performed by the reverse technique. FVIII activity was measured through coagulometric method, and VWF and ADAMTS13 antigens were assessed by ELISA. FVIII activity and VWF levels were significantly higher and ADAMTS13 levels was decreased in HD patients, as compared to healthy subjects (P < 0.001, in three cases). HD patients carrying non-O blood groups showed a significant increase in FVIII activity (P = 0.001) and VWF levels (P < 0.001) when compared to carriers of O blood group. However, no significant difference was observed in ADAMTS13 levels (P = 0.767). In the control group, increased in FVIII activity (P = 0.001) and VWF levels (P = 0.002) and decreased in ADAMTS13 levels (P = 0.005) were observed in subjects carrying non-O blood groups as compared to carriers of O blood group.Our data confirmed that ABO blood group is an important risk factor for increased procoagulant factors in plasma, as FVIII and VWF. Admitting the possible role of kidneys in ADAMTS13 synthesis or on its metabolism, HD patients were not able to increase ADAMTS13 levels in order to compensate the increase of VWF levels mediated by ABO blood groups. Considering that non-O blood groups constitute a risk factor for thrombosis, it is reasonable to admit that A, B and AB HD patients need a careful and continuous follow-up in order to minimize thrombotic events.

ADAMTS13 and Von Willebrand factor in patients undergoing hemodialysis.

Hemodialysis (HD) is associated with increasing thrombotic trend. Vascular access thrombosis (VAT) increases morbidity in HD patients. The aim of this study was to evaluate ADAMTS13 and VWF plasma levels from patients undergoing HD as putative biomarkers of the hypercoagulability state, as well the association between these markers and VAT occurrence. This study included 195 patients on HD for more than 6 months. HD patients were allocated into two groups according to the occurrence or not of previous episode of VAT; HD with VAT (N = 46) and HD without VAT (N = 149). ADAMTS13 and VWF were performed by ELISA. There was no significant difference between HD patients with and without VAT for ADAMTS13 and VWF levels. However, VWF levels were higher (P < 0.001) and ADAMTS13 were lower (P < 0.001) in HD patients, comparing to the control group composed by healthy subjects without kidney disease, age and sex-matched (N = 80). Taken together our data suggest a potential role of the kidneys function compromised on ADAMTS13 synthesis or metabolism, regardless other known sources of ADAMTS13. The imbalance between ADAMTS13 and VWF levels does not explain the development of VAT in HD patients by itself, although it should contribute for the hypercoagulability state. Therefore, additional studies to identify other risk factors are warranted and essential for better management of HD patients.

Childhood obesity: evidence of an association between plasminogen activator inhibitor-1 levels and visceral adiposity.

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) has been considered as a cardiovascular risk factor, mainly because of its strong association with insulin resistance. METHODS: To detect independent predictors of circulating PAI-1 levels in obese pediatric patients, we evaluated 86 subjects (mean age 10.7 +/- 2.8 years), 42 of whom were male (49%). Subjects were divided in two groups according to body mass index (BMI): obese subjects (n=61) and healthy non-obese controls (n=25). They were also divided by pubertal status. Besides anthropometric data, levels of PAI-1, leptin and biochemical markers of metabolic syndrome were measured. RESULTS: The obese group had higher levels of PAI-1, leptin and biochemical markers of metabolic syndrome than nonobese controls (p<0.05). However, multivariate regression analysis showed that only puberty progression (p=0.005) and abdominal circumference/height index (p=0.002) remained independent predictors of PAI-1 levels. CONCLUSION: In pediatric obesity, fat mass accumulation, mainly of visceral fat, and puberty progression were related to high PAI-1 levels, which might in turn contribute to cardiovascular risk.

Hemodialysis vascular access thrombosis: The role of factor V Leiden, prothrombin gene mutation and ABO blood groups.

BACKGROUND: Vascular access thrombosis increases morbidity in hemodialysis (HD) patients. The aim of this study was to investigate the association between HD vascular access thrombosis and mutations in the prothrombin and factor V Leiden (FV) genes and ABO blood system. METHODS: This cross-sectional study included 195 patients with end stage renal disease (ESRD) on HD for more than six months. HD patients were allocated into two groups according to the occurrence (cases, N=46) or not (controls, N=149) of previous vascular access thrombosis. FV and prothrombin gene mutations were investigated by polymerase chain reaction and ABO blood group phenotyping was performed by the indirect technique. Univariate analysis detected the variables with a trend to be associated with thrombosis and was followed by multivariate analysis to define independent predictors of vascular access thrombosis. RESULTS: FV Leiden mutation and ABO blood group were not associated with vascular access thrombosis, whereas G20210A mutation in the prothrombin gene was significantly higher in patients with vascular access thrombosis and independently associated with this complication (OR=12.0; CI 95%=1.8-83.5; p=0.012). CONCLUSIONS: G20210A mutation emerges as an important genetic factor predisposing to vascular access thrombosis. The definition of risk factors for thrombosis will certainly enable a rational approach for HD patients.

Pre-eclampsia: relationship between coagulation, fibrinolysis and inflammation.

Pre-eclampsia (PE) is a multi-system disorder of human pregnancy, characterised by hypertension and proteinuria. Although the pathogenesis of PE is not fully understood, predisposition to endothelial dysfunction is thought to play a crucial part. Despite intensive research there is no reliable test for screening purposes or to inform decision making towards effective treatment for PE. Understanding the link between PE, abnormal haemostatic activation and inflammation may help to elucidate some of the patho-physiology of the disease; primary preventative measures and targeted therapies at an early stage of the disease could then be considered. In the present paper we discuss potential causal links between PE, haemostasis and inflammation. The potential implications of such interaction on the pathogenesis of PE are also addressed.

Púrpura trombocitopênica trombótica: o papel do fator von Willebrand e da ADAMTS13 / Thrombotic thrombocytopenic purpura: the role of von Willebrand factor and ADAMTS13

A púrpura trombocitopênica trombótica (PTT) instala-se de modo abrupto e é caracterizada pela oclusão difusa de arteríolas e capilares da microcirculação, levando à isquemia de tecidos. A oclusão é causada por microtrombos compostos basicamente de plaquetas e fator von Willebrand (FvW). O FvW é uma glicoproteína de estrutura multimérica sintetizada exclusivamente por células endoteliais e megacariócitos. Este fator promove a adesão das plaquetas ao endotélio lesado, participa do processo de agregação plaquetária e é a proteína carreadora do fator VIII na circulação. Em condições fisiológicas, os grandes multímeros do FvW encontram-se dentro das células endoteliais e nas plaquetas e não estão presentes no plasma. Tão logo estes grandes multímeros são liberados da célula endotelial, são clivados e removidos da circulação pela enzima ADAMTS13 (A Desintegrin And Metalloprotease with eight Thrombo Spondin-1-like). A deficiência funcional ou quantitativa de ADAMTS13 resulta no acúmulo de grandes multímeros de FvW no plasma, propiciando a agregação das plaquetas e oclusão difusa das arteríolas e capilares. A maioria dos casos de PTT está associada à deficiência da ADAMTS13 e já estão disponíveis no mercado internacional conjuntos diagnósticos para a determinação dos níveis de antígenos desta enzima, da de sua atividade e dos anticorpos anti-ADAMTS13. A avaliação laboratorial da ADAMTS13 parece constituir um avanço para o diagnóstico precoce da PTT. No entanto, a interpretação dos resultados exige cautela e um conhecimento do princípio do método, bem como das etapas das reações envolvidas.

Thrombotic thrombocytopenic purpura (TTP) starts abruptly and is characterized by diffuse occlusion of microcirculation arterioles and capillaries, leading to ischemia of tissues. Occlusion is caused by microscopic clots primarily composed of platelets and von Willebrand factor (VWF). VWF is a multimeric glycoprotein synthesized exclusively by endothelial cells and megakaryocytes. This factor promotes adhesion of platelets to injured endothelium, participates in the process of platelet aggregation and is the carrier protein of factor VIII in the circulation. In physiological conditions, large VWF multimers are present in endothelial cells and platelets and are not present in plasma. As soon as these large multimers are released from the endothelial cell, they are cleaved and removed from circulation by the ADAMTS13 enzyme. A quantitative or functional deficiency of ADAMTS13 results in the accumulation of large VWF multimers in the plasma and may result in the aggregation of platelets and diffuse occlusion of arterioles and capillaries. Most cases of PTT are associated with ADAMTS13 deficiency. The levels of antigens, activity and antibodies of MTS13 can be evaluated using internationally manufactured kits. The laboratory evaluation of ADAMTS13 appears to be a useful tool for the early diagnosis of PTT. However, interpretation of the results requires caution, as well as knowledge of the principles of the method and the steps of the reactions involved.

Effects of isoflavones on the coagulation and fibrinolytic system of postmenopausal women.

OBJECTIVE: We evaluated the effects of soy isoflavone supplementation on hemostasis in healthy postmenopausal women. METHODS: In this double-blinded, placebo-controlled study, 47 postmenopausal women 47-66 y of age received 40 mg of soy isoflavone (n = 25) or 40 mg of casein placebo (n = 22) once a day for 6 mo. Levels of factors VII and X, fibrinogen, thrombin-antithrombin complex, prothrombin fragments 1 plus 2, antithrombin, protein C, total and free protein S, plasminogen, plasminogen activator inhibitor-1, and D-dimers were measured at baseline and 6 mo. Urinary isoflavone concentrations (genistein and daidzein) were measured as a marker of compliance and absorption using high-performance liquid chromatography. Baseline characteristics were compared by unpaired Student's t test. Within-group changes and comparison between the isoflavone and casein placebo groups were determined by a mixed effects model. RESULTS: The levels of hemostatic variables did not change significantly throughout the study in the isoflavone group; however, the isoflavone group showed a statistically significant reduction in plasma concentration of prothrombin fragments 1 plus 2; both groups showed a statistically significant reduction in antithrombin, protein C, and free protein S levels. A significant increase in D-dimers was observed only in the isoflavone group. Plasminogen activator inhibitor-1 levels increased significantly in the placebo group. However, these changes were not statistically different between groups. CONCLUSION: The results of the present study do not support a biologically significant estrogenic effect of soy isoflavone on coagulation and fibrinolysis in postmenopausal women. However, further research will be necessary to definitively assess the safety and efficacy of isoflavone.