ABSTRACT Objective This study aimed to evaluate inflammatory biomarkers in patients undergoing peritoneal dialysis and investigate their association with all-cause mortality or transfer to hemodialysis. Methods This prospective cohort study included 43 patients undergoing peritoneal dialysis. Plasma levels of cytokines were measured using flow cytometry and capture enzyme-linked immunosorbent assay. Biomarkers were categorized based on their respective median values. Survival analysis was conducted using the Kaplan-Meier estimator, considering two outcomes: all-cause mortality and transfer to hemodialysis. Results After adjusting for confounding factors, plasma levels above the median of the levels of CCL2 and plasma, as well as below the median of TNF-α, and the median of dialysate IL-17 levels, were associated with an increased risk of experiencing the specified outcomes after approximately 16 months of follow-up. Conclusion These findings suggest that inflammatory biomarkers may be a valuable tool for predicting all-cause mortality and transfer to hemodialysis in patients undergoing peritoneal dialysis. allcause all cause 4 enzymelinked enzyme linked assay values KaplanMeier Kaplan Meier estimator factors CCL TNFα, TNFα TNF α, α TNF-α IL17 IL 17 IL-1 1 followup. followup follow up. up follow-up IL1 IL-

Resumo As doenças cardiovasculares (DCV) são a principal causa de morte em todo o mundo, o que gera um fardo económico significativo de bilhões por ano no sistema de saúde. A inflamação crônica é conhecida por sua importância na patogênese da aterosclerose e das DCV. Atualmente, os índices hematológicos inflamatórios, obtidos através dos resultados do hemograma completo (HC), têm sido caracterizados como potenciais fatores prognósticos para mortalidade nas DCV. Esses índices são calculados a partir da contagem de neutrófilos, linfócitos, plaquetas e monócitos, são de fácil acesso, possuem cálculos simples e têm baixo custo, o que facilita sua aplicação na prática. O objetivo deste trabalho foi preparar uma síntese de estudos que investigaram a relação dos índices hematológicos com o risco cardiovascular e mortalidade. A busca foi realizada nas bases de dados PubMed, Scopus, Embase, Web of Science e Biblioteca Virtual em Saúde (BVS). Foram selecionados estudos que investigaram a associação entre índices hematológicos inflamatórios com risco cardiovascular e mortalidade. Foram obtidos 1.470 estudos na busca, sendo apenas 23 elegíveis. Descobrimos que o índice hematológico mais associado à mortalidade geral, eventos cardiovasculares e mortalidade cardiovascular foi o índice de inflamação imunológica sistêmica (SII), seguido pelo índice de resposta inflamatória sistêmica (SIRI). Os índices inflamatórios hematológicos mostraram-se vantajosos para triagem e identificação de pacientes com alto risco cardiovascular e risco de mortalidade, podendo ser úteis no direcionamento do tratamento desses pacientes, na obtenção de informações sobre prognóstico e na melhoria da estratificação de risco. DCV (DCV mundo saúde Atualmente HC, HC , (HC) neutrófilos linfócitos monócitos acesso custo prática PubMed Scopus Embase BVS. BVS . (BVS) 1470 1 470 1.47 2 elegíveis geral SII, SII (SII) SIRI. SIRI (SIRI) mostraramse mostraram se (HC (BVS 147 47 1.4 (SII (SIRI 14 4 1.

Abstract Cardiovascular diseases (CVDs) are the leading cause of death worldwide, which generates a significant economic burden of billions per year on the healthcare system. Chronic inflammation is known for its importance in the pathogenesis of atherosclerosis and CVDs. Currently, inflammatory hematologic indices, obtained through the results of the complete blood count (CBC), have been characterized as potential prognostic factors for mortality in CVD. These indexes are calculated from neutrophil, lymphocyte, platelet, and monocyte counts, are easily accessible, have simple calculations, and have low cost, which facilitates their application in practice. The aim of this paper was prepare a synthesis of studies that investigated the relationship of inflammatory hematologic indices with cardiovascular risk and mortality. The search was been conducted in PubMed, Scopus, Embase, Web of Science, and Virtual Health Library (VHL) databases. Studies that investigated the association between inflammatory hematologic indices with cardiovascular risk and mortality were been selected. 1,470 studies were obtained in the search, with only 23 being eligible. We found that the hematological index most associated with overall mortality, cardiovascular events, and cardiovascular mortality was the systemic immune-inflammation index (SII) followed by the systemic inflammatory response index (SIRI). The hematological inflammatory indices proved advantageous for screening and identifying patients who have high cardiovascular risk and mortality risk, and may be useful in directing the treatment of these patients, obtaining information about prognosis, and improving risk stratification. CVDs (CVDs worldwide system Currently CBC, CBC , (CBC) CVD neutrophil lymphocyte platelet counts accessible calculations cost practice PubMed Scopus Embase Science VHL (VHL databases selected 1470 1 470 1,47 2 eligible events immuneinflammation immune SII (SII SIRI. SIRI . (SIRI) prognosis stratification (CBC 147 47 1,4 (SIRI 14 4 1,

ABSTRACT Objective This study aimed to compare the hematological parameters released by hematological analyzers with those released in customer reports. Methods We conducted a descriptive study in the laboratories of a medium-sized municipality in the state of Minas Gerais registered in the National Register of Health Establishments. Interviews were conducted using a questionnaire to obtain information regarding the parameters released by the analyzers and those available in the customer’s report. Results Sixteen laboratories were evaluated, and none of them released all the parameters obtained from the hematological analyzers to customers. The red blood cell distribution width was released in 88% of the laboratories, atypical lymphocytes in 70%, mean platelet volume in 50%, platelet distribution width and platelet count in 20%. No laboratory released information on reticulocytes, fraction of immature reticulocytes and immature granulocytes, nucleated erythrocyte count, immature platelet fraction and reticulocyte hemoglobin, and large platelet rate. Conclusion All evaluated clinical analysis laboratories had at least one parameter that was not released in the customer’s report despite being released by the hematological analyzers. The lack of knowledge on the part of professionals about the clinical importance of each parameter of the complete blood count results in a loss in patient assessment, and it is important to include these parameters in the complete blood count report. reports mediumsized medium sized Establishments customers s 88 70 70% 50 50% 20 20% granulocytes hemoglobin rate assessment 8 7 5 2

Abstract Background Warfarin is the only oral anticoagulant available in the Brazilian public health system. Health knowledge and treatment are essential to achieving the desirable therapeutic effect. However, data on these aspects among primary care patients are still lacking. Objective To assess health literacy, patient knowledge, and adherence to oral anticoagulation with warfarin, as well as the medication regimen complexity in primary health units in the municipality of Divinópolis, Minas Gerais, Brazil. Methods This cross-sectional study included patients using warfarin from primary care settings. Sociodemographic and clinical data were collected from medical records. Short Assessment of Health Literacy for Portuguese-Speaking Adults (SAHLPA-18), Oral Anticoagulation Knowledge (OAK), adaptation of the Measure of Adherence to Treatment (MAT-adapted) to oral anticoagulation, and Medication Regimen Complexity Index (MRCI) were applied, and the time in therapeutic range (TTR) was calculated. Patients were stratified in two groups (TTR < 60% and TTR ≥ 60%) and compared using Fisher's exact test at a significance level of p < 0.050. Results Analysis included 162 patients (64.8 ± 12.7 years old, 55.6% women). Nonvalvular atrial fibrillation (26.5%) and venous thromboembolism (24.1%) were the main indications for warfarin, and 67.9%, 88.3%, and 16.7% of the patients had inadequate health literacy, insufficient knowledge regarding anticoagulant therapy, and non-adherence to warfarin therapy, respectively. There was no significant association of these parameters in relation to TTR. MRCI showed high pharmacotherapy complexity between the drug prescriptions. Conclusion This study showed alarming insufficient knowledge about warfarin therapy and low health literacy in primary care patients. system effect However lacking Divinópolis Gerais Brazil crosssectional cross sectional settings records PortugueseSpeaking Portuguese Speaking SAHLPA18, SAHLPA18 SAHLPA 18 , (SAHLPA-18) OAK, OAK (OAK) MATadapted MAT adapted (MAT-adapted (MRCI applied calculated 60 Fishers Fisher s 0050 0 050 0.050 16 64.8 648 64 8 (64. 127 12 7 12. old 556 55 6 55.6 women. women . women) 26.5% 265 26 5 (26.5% 24.1% 241 24 1 (24.1% 679 67 9 67.9% 883 88 3 88.3% 167 16.7 nonadherence non respectively prescriptions SAHLPA1 (SAHLPA-18 (OAK 005 05 0.05 64. (64 55. 26.5 2 (26.5 24.1 (24.1 67.9 88.3 16. (SAHLPA-1 00 0.0 (6 26. (26. 24. (24. 67. 88. (SAHLPA- 0. ( (26 (24 (SAHLPA (2

Resumo Fundamento Apesar da ausência de evidência mostrando benefícios da hidroxicloroquina e da cloroquina combinadas ou não à azitromicina no tratamento da covid-19, esses medicamentos têm sido amplamente prescritos no Brasil. Objetivos Avaliar desfechos, incluindo moralidade hospitalar, alterações eletrocardiográficas, tempo de internação, admissão na unidade de terapia intensiva, e necessidade de diálise e de ventilação mecânica em pacientes hospitalizados com covid-19 que receberam cloroquina ou hidroxicloroquina, e comparar os desfechos entre aqueles pacientes e seus controles pareados. Métodos Estudo multicêntrico retrospectivo do tipo coorte que incluiu pacientes com diagnóstico laboratorial de covid-19 de 37 hospitais no Brasil de março a setembro de 2020. Escore de propensão foi usado para selecionar controles pareados quanto a idade, sexo, comorbidades cardiovasculares, e uso de corticosteroides durante a internação. Um valor de p<0,05 foi considerado estatisticamente significativo. Resultados Dos 7850 pacientes com covid-19, 673 (8,6%) receberam hidroxicloroquina e 67 (0,9%) cloroquina. A idade mediana no grupo de estudo foi 60 (46-71) anos e 59,1% eram mulheres. Durante a internação, 3,2% dos pacientes apresentaram efeitos adversos e 2,2% necessitaram de interromper o tratamento. Alterações eletrocardiográficas foram mais prevalentes no grupo hidroxicloroquina/cloroquina (13,2% vs. 8,2%, p=0,01), e o prolongamento do intervalo QT corrigido foi a principal diferença (3,6% vs. 0,4%, p<0,001). O tempo mediano de internação hospitalar foi maior no grupo usando CQ/HCQ em relação aos controles (9,0 [5,0-18,0] vs. 8,0 [4,0-14,0] dias). Não houve diferenças estatisticamente significativas entre os grupos quanto a admissão na unidade de terapia intensiva (35,1% vs. 32,0%; p=0,282), ventilação mecânica invasiva (27,0% vs. 22,3%; p=0,074) ou mortalidade (18,9% vs. 18,0%; p=0,682). Conclusão Pacientes com covid-19 tratados com cloroquina ou hidroxicloroquina apresentaram maior tempo de internação hospitalar, em comparação aos controles. Não houve diferença em relação a admissão em unidade de terapia intensiva, necessidade de ventilação mecânica e mortalidade hospitalar. covid19, covid19 covid 19, 19 covid-1 3 2020 sexo cardiovasculares p005 p 0 05 p<0,0 significativo 785 8,6% 86 8 6 (8,6% 0,9% 09 9 (0,9% 4671 46 71 (46-71 591 59 1 59,1 mulheres 32 2 3,2 22 2,2 hidroxicloroquinacloroquina 13,2% 132 13 (13,2 vs 82 8,2% p=0,01, p001 p=0,01 , 01 p=0,01) 3,6% 36 (3,6 04 4 0,4% p<0,001. p0001 p<0,001 . 001 p<0,001) CQHCQ CQ HCQ 9,0 90 (9, 5,018,0 50180 5,0 18,0 5 18 [5,0-18,0 80 8, 4,014,0 40140 4,0 14,0 14 [4,0-14,0 dias. dias dias) 35,1% 351 35 (35,1 32,0% 320 p=0,282, p0282 p=0,282 282 p=0,282) 27,0% 270 27 (27,0 22,3% 223 p=0,074 p0074 074 18,9% 189 (18,9 18,0% 180 p=0,682. p0682 p=0,682 682 p=0,682) covid1 covid- 202 p00 p<0, 78 8,6 (8,6 0,9 (0,9 467 7 (46-7 59, 3, 2, 13,2 (13, 8,2 p=0,0 3,6 (3, 0,4 p000 p<0,00 00 9, (9 018 5,018, 5018 50 5, 18, [5,0-18, 014 4,014, 4014 40 4, 140 14, [4,0-14, 35,1 (35, 32,0 p028 p=0,28 28 27,0 (27, 22,3 p=0,07 p007 07 18,9 (18, p068 p=0,68 68 20 p0 p<0 (8, 0, (0, (46- 13, (13 p=0, (3 ( 5,018 501 [5,0-18 4,014 401 [4,0-14 35, (35 32, p02 p=0,2 27, (27 22, (18 p06 p=0,6 p< (8 (0 (46 (1 p=0 5,01 [5,0-1 4,01 [4,0-1 (2 (4 p= [5,0- [4,0- [5,0 [4,0 [5, [4, [5 [4 [

Abstract Background Despite no evidence showing benefits of hydroxychloroquine and chloroquine with or without azithromycin for COVID-19 treatment, these medications have been largely prescribed in Brazil. Objectives To assess outcomes, including in-hospital mortality, electrocardiographic abnormalities, hospital length-of-stay, admission to the intensive care unit, and need for dialysis and mechanical ventilation, in hospitalized COVID-19 patients who received chloroquine or hydroxychloroquine, and to compare outcomes between those patients and their matched controls. Methods A retrospective multicenter cohort study that included consecutive laboratory-confirmed COVID-19 patients from 37 Brazilian hospitals from March to September 2020. Propensity score was used to select matching controls by age, sex, cardiovascular comorbidities, and in-hospital use of corticosteroid. A p-value <0.05 was considered statistically significant. Results From 7,850 COVID-19 patients, 673 (8.6%) received hydroxychloroquine and 67 (0.9%) chloroquine. The median age in the study group was 60 years (46 - 71) and 59.1% were women. During hospitalization, 3.2% of patients presented side effects and 2.2% required therapy discontinuation. Electrocardiographic abnormalities were more prevalent in the chloroquine/hydroxychloroquine group (13.2% vs. 8.2%, p=0.01), and the long corrected QT interval was the main difference (3.6% vs. 0.4%, p<0.001). The median hospital length of stay was longer in the HCQ/CQ + AZT group than in controls (9.0 [5.0, 18.0] vs. 8.0 [4.0, 14.0] days). There was no statistical differences between groups in intensive care unit admission (35.1% vs. 32.0%; p=0.282), invasive mechanical ventilation support (27.0% vs. 22.3%; p=0.074) or mortality (18.9% vs. 18.0%; p=0.682). Conclusion COVID-19 patients treated with chloroquine or hydroxychloroquine had a longer hospital length of stay, when compared to matched controls. Intensive care unit admission, invasive mechanical ventilation, dialysis and in-hospital mortality were similar. COVID19 COVID 19 COVID-1 treatment Brazil inhospital lengthofstay, lengthofstay length-of-stay laboratoryconfirmed laboratory confirmed 3 2020 sex comorbidities corticosteroid pvalue p value 005 0 05 <0.0 significant 7850 7 850 7,85 8.6% 86 8 6 (8.6% 0.9% 09 9 (0.9% 46 (4 71 591 59 1 59.1 women hospitalization 32 2 3.2 22 2.2 discontinuation chloroquinehydroxychloroquine 13.2% 132 13 (13.2 vs 82 8.2% p=0.01, p001 p=0.01 , 01 p=0.01) 3.6% 36 (3.6 04 4 0.4% p<0.001. p0001 p<0.001 . 001 p<0.001) HCQCQ HCQ CQ 9.0 90 (9. 5.0, 50 5 [5.0 18.0 180 18 80 8. 4.0, 40 [4.0 14.0 140 14 days. days days) 35.1% 351 35 (35.1 32.0% 320 p=0.282, p0282 p=0.282 282 p=0.282) 27.0% 270 27 (27.0 22.3% 223 p=0.074 p0074 074 18.9% 189 (18.9 18.0% p=0.682. p0682 p=0.682 682 p=0.682) similar COVID1 COVID- 202 00 <0. 785 85 7,8 8.6 (8.6 0.9 (0.9 ( 59. 3. 2. 13.2 (13. 8.2 p00 p=0.0 3.6 (3. 0.4 p000 p<0.00 9. (9 5.0 [5. 18. 4.0 [4. 14. 35.1 (35. 32.0 p028 p=0.28 28 27.0 (27. 22.3 p=0.07 p007 07 18.9 (18. p068 p=0.68 68 20 <0 78 7, (8. 0. (0. 13. (13 p0 p=0. (3 p<0.0 5. [5 4. [4 35. (35 32. p02 p=0.2 27. (27 22. (18 p06 p=0.6 < (8 (0 (1 p=0 p<0. [ (2 p= p<0 p<

ABSTRACT BACKGROUND: The thrombin generation test (TGT) has shown promise for investigation of hemorrhagic and thrombotic diseases. However, despite its potential, it still needs standardization. Moreover, few studies have established reference values for TGT parameters. In Brazil, these values have not yet been established. OBJECTIVE: To determine TGT performance and reference intervals for TGT parameters in healthy individuals. DESIGN AND SETTING: Cross-sectional study conducted among participants in the Brazilian Longitudinal Study of Adult Health (Estudo Longitudinal de Saúde do Adulto, ELSA-Brasil). METHODS: The reference sample consisted of 620 healthy individuals. The calibrated automated thrombogram (CAT) method, under low and high tissue factor (TF) conditions, was used to assess thrombin generation. Test performance was analyzed using intra and interassay coefficients of variation (CV) and reference intervals were calculated using the nonparametric method proposed by the International Federation of Clinical Chemistry and the Clinical and Laboratory Standards Institute. RESULTS: The intraassay CV ranged from 1.4% to 2.2% and the interassay CV, 6.8% to 14.7%. The reference intervals for TGT parameters under low and high TF conditions were, respectively: lagtime: 3.0-10.3 and 1.4-3.7 min; endogenous thrombin potential (ETP): 1134.6-2517.9 and 1413.6-2658.0 nM.min; normalized ETP: 0.6-1.3 and 0.7-1.4; peak: 103.2-397.7 and 256.4-479.0 nM; normalized peak: 0.3-1.3 and 0.7-1.2; and time-to-peak: 5.6-16.0 and 3.4-6.7 min. These parameters were categorized relative to sex. Conclusion: TGT performance was adequate and the proposed reference intervals were similar to those of other studies. Our findings may be useful for consolidating the TGT, through contributing to its standardization and validation.

Resumo Introdução: Estudos têm mostrado que o sistema renina angiotensina aldosterona (SRAA) e a inflamação estão relacionados à progressão da lesão renal. O objetivo deste estudo foi avaliar moléculas do SRAA e o Ligante 2 de Quimiocina com Motivo C-C (CCL2) em 82 pacientes com doença renal crônica (DRC). Métodos: Os pacientes foram divididos em dois grupos: pacientes diagnosticados com DRC e pacientes sem diagnóstico de DRC. Foram determinadas a taxa de filtração glomerular (TFG) e a relação albumina/creatinina (RAC), assim como os níveis plasmáticos de angiotensina-(1-7) [Ang-(1-7)], enzima conversora de angiotensina (ECA)1, ECA2 e níveis plasmáticos e urinários de CCL2. Resultados: Os níveis plasmáticos de CCL2 foram significativamente mais altos em pacientes com DRC em comparação com o grupo controle. Pacientes com TFG mais baixa apresentaram níveis plasmáticos mais elevados de ECA2 e CCL2 e menor relação ECA1/ECA2. Pacientes com valores de RAC mais altos apresentaram níveis plasmáticos de ECA1 mais elevados. Conclusão: Pacientes com DRC mostraram maior atividade de ambos os eixos do SRAA, o clássico e o alternativo, e níveis plasmáticos mais altos de CCL2. Portanto, os níveis plasmáticos de moléculas do SRAA e CCL2 parecem ser marcadores prognósticos promissores e até mesmo alvos terapêuticos para a DRC.

Abstract Introduction: Studies have shown that the renin angiotensin aldosterone system (RAAS) and inflammation are related to kidney injury progression. The aim of this study was to evaluate RAAS molecules and chemokine (C-C motif) ligand 2 (CCL2) in 82 patients with chronic kidney disease (CKD). Methods: Patients were divided into two groups: patients diagnosed with CKD and patients without a CKD diagnosis. Glomerular filtration rate (GFR) and albumin/creatinine ratio (ACR) were determined, as well as plasma levels of angiotensin-(1-7) [Ang-(1-7)], angiotensin-converting enzyme (ACE)1, ACE2, and plasma and urinary levels of CCL2. Results: CCL2 plasma levels were significantly higher in patients with CKD compared to the control group. Patients with lower GFR had higher plasma levels of ACE2 and CCL2 and lower ratio ACE1/ACE2. Patients with higher ACR values had higher ACE1 plasma levels. Conclusion: Patients with CKD showed greater activity of both RAAS axes, the classic and alternative, and higher plasma levels of CCL2. Therefore, plasma levels of RAAS molecules and CCL2 seem to be promising prognostic markers and even therapeutic targets for CKD.

ABSTRACT Objective To identify and analyze the quality of scientific evidence from clinical efficacy studies present in the package inserts of coagulation factors, used in the treatment of hemophilia A and B. Methods Documentary study developed in two stages. The first stage consisted of identifying the medicine packages inserts electronically registered in the Brazilian Health Regulatory Agency, and analyzing the availability of the bibliographic references cited therein. This analysis was conducted in the PubMed, SciELO, Google Scholar, and Web of Science databases. The second step was the analysis of the methodological quality of the efficacy studies. Two trained researchers used the Cochrane Collaboration Risk of Bias version 5.1.0 tools for methodological quality analysis, and Review Manager 5.4 software to generate the risk of bias graph. Results Of the 17 medicines listed, 7 had referenced package inserts. Of these, 10 studies were eligible for analysis of methodological quality. More than half of the analyzed studies did not control for selection, performance, and detection bias. A total of 100% controlled attrition and reporting biases, and 50% had a high risk of conflict of interest. Conclusion The biases present are significant and may have influenced the overestimation of the effects of the outcomes of each of the studies.

Resumo Introdução: Alterações estruturais progressivas na membrana peritoneal ocorrem no decorrer do tratamento em diálise peritoneal (DP), resultando em um aumento de citocinas como CCL2 e alterações estruturais na membrana peritoneal desencadeando um aumento de CA-125 no dialisato, o que reflete um provável processo inflamatório local, com possível perda de células mesoteliais. Assim, o presente estudo teve como objetivo avaliar a associação entre CCL2 e CA-125 no plasma e no dialisato de pacientes submetidos à DP. Métodos: Foi realizado um estudo transversal com 41 pacientes submetidos à DP. As avaliações dos níveis de CA-125 e CCL2 foram realizadas utilizando ELISA de captura. As correlações foram estimadas usando a correlação de Spearman, e a investigação da associação entre as variáveis explicativas (CCL2) e a variável resposta (CA-125) foi feita pela razão bruta das médias aritméticas e ajustada utilizando modelos lineares generalizados. Resultados: Foi observada uma correlação positiva moderada entre os níveis de CA-125 e CCL2 no dialisato (rho = 0,696). Foi encontrada uma associação estatisticamente significativa entre os níveis no dialisato de CCL2 e CA-125 (RoM=1,31; IC = 1,20-1,43), que permaneceu após ajuste por idade (RoM = 1,31; IC=1,19-1,44) e pelo tempo de DP em meses (RoM=1,34, IC=1,22-1,48). Conclusão: A associação dos níveis de CA-125 com CCL2 no dialisato pode indicar que o processo inflamatório local leva a alterações temporárias ou definitivas na membrana peritoneal. Uma melhor compreensão desta patogênese pode contribuir para a descoberta de novos biomarcadores inflamatórios.

Abstract Introduction: Progressive structural changes in the peritoneal membrane occur over the course of treatment in peritoneal dialysis (PD), resulting in an increase in cytokines such as CCL2 and structural changes in peritoneal membrane triggering an increase in CA-125 in dialysate, which reflects a probable local inflammatory process, with possible loss of mesothelial cells. Thus, the current study aimed to evaluate the association between plasma and CCL2 and CA-125 dialysate levels in patients undergoing PD. Methods: Cross-sectional study was conducted with 41 patients undergoing PD. The assessments of CA-125 and CCL2 levels were performed using a capture ELISA. Correlations were estimated using Spearman's correlation and the investigation of the association between the explanatory variables (CCL2) and response variable (CA-125) was done for crude ratio of arithmetic means and adjusted utilizing generalized linear models. Results: A moderate positive correlation was observed between the levels of CA-125 and CCL2 in the dialysate (rho = 0.696). A statistically significant association was found between the levels in the CCL2 and CA-125 dialysate (RoM=1.31; CI = 1.20-1.43), which remained after adjustment for age (RoM = 1.31; CI=1.19-1.44) and for time in months of PD (RoM=1.34, CI=1.22-1.48). Conclusion: The association of CA-125 levels with CCL2 in the dialysate may indicate that the local inflammatory process leads to temporary or definitive changes in peritoneal membrane. A better understanding of this pathogenesis could contribute to the discovery of new inflammatory biomarkers.

ABSTRACT Background: In order to standardize a thrombin generation() protocol, we analyzed the analytical variables and sensitivity of this test to hypo/hypercoagulability states. Methods: The effect of the tissue factor concentration and the intra- and interassay precision were analyzed. To evaluate the hypercoagulability status, the plasma of women under an oral contraceptive was tested, while plasma from hemophilia A patients at 1, 3 and 7 days after recombinant FVIII infusion, and lyophilized plasma deficient in FVII or FVIII were used for the evaluation of hypocoagulability. Results: The intra-assay coefficient of variation was <10% with 1 and 5 pM of low and high TF. The oral contraceptive users showed increased thrombin generation in comparison to non-users, which was more pronounced with low TF (endogenous thrombin potential ETP) p = 0.0009; peak p = 0.0009; lagtime p = 0.0008). In relation to the FVIII-deficient plasma, a higher TG was observed as FVIII levels were increased and a better discrimination was obtained for different concentrations of FVIII with low TF (ETP p < 0.0001; peak p < 0.0001; lagtime p = 0.0004). Using low TF, plasma from hemophilia A patients showed higher TG values after 1 day of recombinant FVIII infusion vs after 3 days (ETP p < 0.0001; peak p < 0.0001; lagtime p = 0.0407), while the lowest values were observed after 7 days. With FVII-deficient plasma, thrombin generation was lower than normal plasma and a more pronounced difference was observed with high TF compared to low TF (ETP p < 0.0001; peak p < 0.0001; lagtime p < 0.0001). Conclusion: Under our conditions the thrombin generation test seems to be sensitive to evaluation of hyper/hypocoagulability states. Standardization of the thrombin generation test may have an application in the evaluation of bleeding and thrombotic disorders.

RESUMO A obesidade, o diabetes e a hipertensão arterial são fatores de risco para as doenças cardiovasculares (DCV) por promoverem um estado de hipercoagulabilidade. É sabido que as plaquetas desempenham um importante papel no desenvolvimento da aterosclerose. Diante disso, estudos recentes têm avaliado os índices de volumes plaquetários (IVPs) em indivíduos com fatores de risco para DCV, para melhor se entenderem os mecanismos plaquetários envolvidos no seu desenvolvimento. Os IVPs estimam indiretamente a função plaquetária e são facilmente obtidos a partir de analisadores hematológicos automáticos, que fornecem contagens de plaquetas, volume médio de plaquetas (VPM), largura de distribuição de plaquetas (PDW) e a proporção de plaquetas grandes (P-LCR). O presente trabalho tem por objetivo revisar na literatura estudos que investigaram a associação entre os IVPs e obesidade, diabetes e hipertensão arterial, a fim de avaliar o seu uso como potencial marcador subclínico das DCV. Estudos demonstraram resultados promissores quanto ao VPM, um índice que permite uma detecção precoce da ativação de plaquetas e que pode ser útil na identificação de pacientes antes do início do desenvolvimento de DCV, de tal forma que estratégias preventivas possam ser implantadas. O PDW, embora tenha sido avaliado por um número menor de estudos, também demonstrou resultados promissores. Entretanto, ainda existe um longo caminho a se percorrer para que o VPM e o PDW sejam utilizados na prática clínica, pois ainda são necessárias mais evidências epidemiológicas, o estabelecimento de valores de referência e a padronização da forma de expressar os resultados.

SUMMARY Obesity, diabetes and hypertension are risk factors for cardiovascular diseases (CVD) because they promote a state of hypercoagulability. It is known that platelets play an important role in the development of atherosclerosis. Recent studies have evaluated platelet volume indexes (PVIs) in individuals with risk factors for CVD to better understand the platelet mechanisms involved in their development. The IVPs indirectly estimate platelet function and are easily obtained from automated hematology analyzers, which provide platelet counts, mean platelet volume (MPV), platelet distribution width (PDW) and the platelet-large cell ratio (P-LCR). The present study aims to review literature studies that investigated the association between PVIs and obesity, diabetes, and arterial hypertension, in order to evaluate its use as a potential subclinical marker of CVD. Studies have shown promising results for MPV, an index that allows for early detection of platelet activation and may be useful in identifying patients before the onset of CVD development so that preventive strategies can be implemented. The PDW, although evaluated by a smaller number of studies, also showed promising results. However, there is still a long way to go in order for the MPV and PDW to be used in clinical practice, since there is still a need for more epidemiological evidence, establishing reference values, and standardizing the way results are presented.

Abstract The existing techniques to evaluate hemostasis in clinical laboratories are not sensitive enough to detect hypercoagulable and mild hypocoagulable states. Under different experimental conditions, the thrombin generation test may meet these requirements. This technique evaluates the overall balance between procoagulant and anticoagulant forces and has provided new insights in our understanding of the coagulation cascade, as well as of the diagnosis of hypocoagulability and hypercoagulability conditions. Thrombin generated in the thrombin generation test can be quantified as platelet-rich or platelet-poor plasma using the calibrated automated thrombogram method, which monitors the cleavage of a fluorogenic substrate that is simultaneously compared to the known thrombin activity in a non-clotting plasma sample. The calibrated automated thrombogram method is an open system, in which different antibodies, proteins, enzymes and peptides can be introduced to answer specific questions regarding hemostatic processes. The thrombin generation test has great clinical potential, such as in monitoring patients taking anticoagulants and antiplatelet drugs, screening for genetic or acquired thrombotic disorders, and evaluating bleeding risk control in patients with hemophilia using bypass agents or replacement therapy. Different to conventional coagulation tests, the thrombin generation test can be used for an overall evaluation of hemostasis, the results of which can then be used to evaluate specific characteristics of hemostasis, such as prothrombin time, activated partial thromboplastin time, and levels of fibrinogen and other coagulation factors. The introduction of this method will contribute to a better understanding and evaluation of overall hemostatic processes; however, this method still requires standardization and clinical validation.

Abstract Objective: This study aimed to describe and analyze clinical and laboratory characteristics of patients with sickle cell anemia treated at the Hemominas Foundation, in Divinópolis, Brazil. Furthermore, this study aimed to compare the clinical and laboratory outcomes of the group of patients treated with hydroxyurea with those patients that were not treated with hydroxyurea. Methods: Clinical and laboratorial data were obtained by analyzing medical records of patients with sickle cell anemia. Results: Data from the medical records of 50 patients were analyzed. Most of the patients were female (56%), aged between 20 and 29 years old. Infections, transfusions, cholecystectomy, splenectomy and systemic arterial hypertension were the most common clinical adverse events of the patients. The most frequent cause of hospitalization was painful crisis. The majority of patients had reduced values of hemoglobin and hematocrit (8.55 ± 1.33 g/dL and 25.7 ± 4.4%, respectively) and increased fetal hemoglobin levels (12 ± 7%). None of the clinical variables was statistically significant on comparing the two groups of patients. Among hematological variables only hemoglobin and hematocrit levels were statistically different between patients treated with hydroxyurea and untreated patients (p-value = 0.005 and p-value = 0.001, respectively). Conclusion: Sickle cell anemia requires treatment and follow-up by a multiprofessional team. A current therapeutic option is hydroxyurea. This drug reduces complications and improves laboratorial parameters of patients. In this study, the use of the drug increased the hemoglobin and hematocrit levels of patients.

Resumo A prevalência da doença renal crônica (DRC) tem aumentado nos últimos anos e vários fatores estão associados à instalação e progressão da DRC, tais como obesidade, hipertensão arterial e diabetes mellitus. Uma das complicações da DRC é a anemia causada principalmente pela deficiência de ferro e de eritropoetina (EPO). Um dos tratamentos para este tipo de anemia é uso de eritropoetina exógena. O paciente com DRC submetido à diálise apresenta um estado inflamatório crônico, provocando uma situação de má resposta à ação medular da EPO, causando anemia, desnutrição, agravamento da aterosclerose e aumento da mortalidade. O objetivo deste artigo foi revisar as evidências científicas referentes à associação da má resposta clínica ao uso de EPO e a presença de inflamação na DRC.

Abstract The prevalence of kidney chronic disease (CKD) has increased in recent years and several risk factors have been associated with the onset and progression of CDK, such as obesity, hypertension and diabetes mellitus. In addition, anemia is one of the complications of CRD, mainly by iron and erythropoietin (EPO) deficiency and the management of this situation is with exogenous erythropoietin, but patients undergoing dialysis present chronic inflammatory process followed by EPO resistance and anemia, malnutrition, worse of atherosclerosis and increased mortality ratio. The aim of this study was to review the association of erythropoietin resistance and chronic inflammatory process in patients with chronic renal disease.

A síndrome do anticorpo antifosfolípide (SAAF) é uma trombofilia autoimune adquirida, caracterizada pela presença de uma família heterogênea de anticorpos que se ligam a proteínas plasmáticas com afinidade, por superfícies fosfolipídicas. As duas principais proteínas-alvo dos anticorpos antifosfolípides (AAF) são a protrombina e a β2-glicoproteína 1 (β2GP1). A SAAF está associada a um estado protrombótico e é clinicamente caracterizada pela ocorrência de trombose arterial, venosa ou microvascular ou perda fetal recorrente. O diagnóstico da SAAF é baseado em um conjunto de critérios clínicos e na detecção plasmática de anticoagulante lúpico (AL), anticorpo anticardiolipina (ACA) ou antiβ2GP1. Embora os testes laboratoriais sejam de fundamental importância para o diagnóstico da SAAF, eles apresentam limitações associadas à robustez, à reprodutibilidade e à padronização. A padronização de testes diagnósticos para a pesquisa de AAF tem sido um desafio, pois uma variedade de resultados pode ser obtida utilizando diferentes kits comerciais e técnicas in-house. Um aumento da sensibilidade dos kits de ELISA para a detecção do ACA contribuiu efetivamente para o diagnóstico da SAAF. No entanto, a falta de especificidade, associada a um número elevado de resultados falso-positivos, é um desafio clínico e laboratorial, uma vez que tais resultados podem levar a decisões clínicas erradas, como a prescrição de anticoagulante oral, levando ao risco de hemorragia. Além disso, os clínicos muitas vezes não estão familiarizados com esses testes e têm dificuldade em interpretá-los, sendo necessária a interação da clínica e dos profissionais do laboratório para assegurar sua correta interpretação.

Antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilia characterized by the presence of a heterogeneous family of antibodies that bind to plasma proteins with affinity for phospholipid surfaces. The two major protein targets of antiphospholipid antibodies are prothrombin and β2-glycoprotein I (β2GPI). APS leads to aprothrombotic state, and it is characterized by the occurrence of arterial, venous or microvascular thrombosis or recurrent fetal loss. The diagnosis of APS is based on a set of clinical criteria and the detection of lupus anticoagulant (LA), anticardiolipin antibodies (ACA) or anti-β2GPI in plasma. Although laboratory tests are essential for APS diagnosis, these tests have limitations associated with the robustness, reproducibility and standardization. The standardization of diagnostic tests for detection of APLAs has been a challenge and a variety of results have been obtained using different commercial kits and in-house techniques. An increased sensitivity of the ELISA kits for detection of ACA effectively has contributed to APS diagnosis. However, the lack of specificity associated with a high number of false-positive results is a clinical and laboratorial challenge, since such results may lead to mistaken clinical decisions, such as prescription of oral anticoagulant, leading to the risk of hemorrhaging. Furthermore, clinicians are often unfamiliar with these tests and have difficulty interpreting them, requiring interaction between clinical and laboratory professionals in order to ensure their correct interpretation.