Asociación entre los niveles séricos de vitamina D y marcadores inflamatorios en pacientes en hemodiálisis / Association between vitamin D serum levels and inflammatory markers in patients on hemodialysis

Resumen Introducción: La relación entre 25-OH-vitamina D y el sistema inmune en pacientes con enfermedad renal crónica es objeto de atención. Objetivos: Evaluar la prevalencia de la deficiencia de vitamina D en pacientes en hemodiálisis e investigar la asociación entre la vitamina D y proteína C reactiva ultrasensible (PCRus), índice neutrófilo/linfocito (INL) e índice plaqueta/linfocito (IPL). Método: Estudio transversal de 80 pacientes en hemodiálisis, divididos en dos grupos: un nivel sérico de 25-OH-vitamina D < 20 ng/mL se consideró como deficiencia de vitamina D y ≥ 20 ng/mL, como normal. Con el análisis de correlación de Spearman se definió la relación entre los parámetros. Resultados: 40 % de los pacientes presentó deficiencia de vitamina D. Hubo diferencias significativas entre los grupos en PCRus (p = 0.047), INL (p = 0.039), IPL (p = 0.042) y tratamiento con análogos de vitamina D (p = 0.022). La vitamina D tuvo una correlación negativa significativa con PCRus (p = 0.026), INL (p = 0.013) e IPL (p = 0.022). Conclusiones: La deficiencia de vitamina D fue de 40 %. Los niveles de PCRus, INL e IPL fueron significativamente más altos ante deficiencia de vitamina D. Se encontró correlación inversa significativa entre vitamina D y PCRus, INL e IPL.

Abstract Introduction: The relationship between 25-OH-vitamin D and the immune system in patients with chronic kidney disease is a subject of attention. Objectives: To assess the prevalence of vitamin D deficiency in patients on hemodialysis and to investigate the association between vitamin D, ultra-sensitive C-reactive protein (US-CRP), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Method: Cross-sectional study of 80 patients on hemodialysis, divided into two groups: a serum 25-OH-vitamin D level < 20 ng/mL was considered to be vitamin D deficiency and a serum level ≥ 20 ng/mL was regarded as normal. The relationship between the parameters was defined with Spearman's correlation analysis. Results: 40 % of the patients had vitamin D deficiency. There were significant differences between groups in US-CRP (p = 0.047), NLR (p = 0.039), PLR (p = 0.042) and treatment with vitamin D analogues (p = 0.022). Vitamin D had a significant negative correlation with US-CRP (p = 0.026), NLR (p = 0.013) and PLR (p = 0.022). Conclusions: The prevalence of vitamin D deficiency was 40 %. The values of US-CRP, NLR and PLR were significantly higher in the presence of vitamin D deficiency. A significant inverse correlation was found between vitamin D levels and US-CRP, NLR and PLR.

Association between Hemogram Parameters and Coronary Collateral Development in Subjects with Non-ST-Elevation Myocardial Infarction

SUMMARY OBJECTIVE Coronary collateral development (CCD) predicts the severity of coronary heart disease. Hemogram parameters, such as mean platelet volume (MPV), eosinophil, red cell distribution width, and platelet distribution width (PDW), are supposed novel inflammatory markers. We aimed to compare hemogram parameter values in patients presenting with non-ST-elevation myocardial infarction (NSTEMI) with adequate or inadequate CCD. METHODS A total of 177 patients with NSTEMI undergoing coronary arteriography were enrolled and divided into two groups based on the development of CCD: one group with adequate CCD (n=88) and the other with impaired CCD (n=89). RESULTS Baseline demographics and clinical risk factors were similar between the groups. Hemogram parameters were not significantly different between the two groups. However, compared to the inadequate CCD group, the median PDW was significantly higher in the adequate CCD group, 17.6 (1.4) vs. 17.8 (1.6) p=0.004. In a multivariate analysis, PDW (p=0.001, 95% CI for OR: 0.489(0,319-0,750) was found to be significantly different in the adequate CCD group compared to the inadequate CCD group. Pearson's correlation analysis revealed that PDW was significantly correlated with the Rentrop score (r=0.26, p<0.001). CONCLUSIONS We suggest that since PDW is an index that is inexpensive and easy to assess, it could serve as a marker of CCD in patients with NSTEMI.

RESUMO OBJETIVO O desenvolvimento colateral coronariano (CCD) prediz a gravidade da doença coronariana. Parâmetros de hemograma como volume plaquetário médio (VPM), eosinófilo, largura de distribuição de glóbulos vermelhos e largura de distribuição de plaquetas (PDW) são supostos novos marcadores inflamatórios. Nosso objetivo foi comparar os valores do parâmetro hemograma em pacientes com infarto do miocárdio sem supradesnivelamento do segmento ST (IAMSSST) com DCC adequado ou inadequado. MÉTODOS Um total de 177 pacientes com NSTEMI submetidos à arteriografia coronariana foram incluídos e divididos, com base no desenvolvimento de CCD, em dois grupos: grupo com CCD adequado (n = 88) e grupo com CCD alterado (n = 89). RESULTADOS Os dados demográficos e os fatores de risco clínicos basais foram semelhantes entre os grupos. Os parâmetros do hemograma não foram significativamente diferentes entre os dois grupos. Mas, em comparação com a mediana inadequada do grupo CCD, o PDW foi significativamente maior em CCD adequado de 17,6 (1,4) vs. 17,8 (1,6) p = 0,004. Na análise multivariada, PDW (p = 0,001, IC 95% para OR: 0,489 (0,319-0,750) foi significativamente diferente no grupo CCD adequado em comparação com o grupo CCD inadequado. A análise de correlação de Pearson revelou que PDW foi significativamente correlacionado com escore de aluguel (r = 0,26, p <0,001). CONCLUSÃO Sugerimos que, uma vez que a PDW é um índice barato e de fácil avaliação, pode servir como um marcador de DCC em pacientes com IAMSSST.

Association of platelet to lymphocyte and neutrophil to lymphocyte ratios with in-hospital mortality in patients with type A acute aortic dissection

Abstract Objective: To evaluate the relationship between neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) with in-hospital mortality in type A acute aortic dissection (AAD). Methods: A total of 96 patients who presented to the emergency department between January 2013 and June 2018 with a diagnosis of type A AAD were enrolled in this study. White blood cell count subtypes such as NLR and PLR were calculated at the time of admission. The end point was in-hospital mortality. Results: Of the 96 type A AAD patients included in this analysis, 17 patients (17.7%) died during hospitalization. NLR and PLR were significantly elevated in patients with type A AAD (P<0.001 and <0.001, respectively). Based on the receiver operating characteristic curve, the best NLR cut-off value to predict in-hospital mortality was 9.74, with 70.6% sensitivity and 76.8% specificity, whereas the best PLR cut-off value was 195.8, with 76.5% sensitivity and 78.1% specificity. Conclusion: Admission NLR and PLR levels were important risk factors and independently associated with in-hospital mortality of type A AAD patients.

High Residual Platelet Reactivity during Aspirin Therapy in Patients with Non-St Segment Elevation Acute Coronary Syndrome: Comparison Between Initial and Late Phases / Alta Atividade Plaquetária Residual em Resposta ao Ácido Acetilsalicílico na Síndrome Coronariana Aguda Sem Supra de ST: Comparação entre as Fases Aguda e Tardia

Abstract Background: High platelet reactivity (HPR) during therapy with acetylsalicylic acid (ASA) is a poor prognostic factor in acute coronary syndromes (ACS). The prevalence of HPR during ACS is greater than that reported in stable diseases. However, it is unclear whether this prevalence of HPR is a transient phenomenon or a characteristic of this high-risk population. Objective: The main objective is to compare the effects of ASA on platelet function in the initial and late phases of ACS in a single population. Secondary objectives are: correlation between the tests between themselves and the relationship between the tests and the variation of the inflammatory markers (C-reactive protein and interleukin-6). Methods: Seventy patients with non-ST segment elevation (NSTE) ACS in use of 100-200 mg of ASA per day for at least 7 days were prospectively studied. Platelet function was assessed in the first 48 hours and subsequently after 3 months using four methods: VerifyNow™ (VFN), whole blood platelet aggregation (WBPA) with arachidonic acid (AA) and collagen as agonists, and platelet function analyzer (PFA). The level of statistical significance considered was < 0.05. Results: According to the more specific methods (WBPA with AA and VFN), the incidence of HPR was significantly higher in the early phase than in the late phase: WBPA with AA: 31% versus 13%, p = 0.015; VFN: 32% versus 16%, p = 0.049. The other methods tested, which were less specific for ASA, did not show significant differences between phases. The correlation between the methods was weak or moderate (r ranging from 0.3 to 0.5, p < 0.05), and there were no significant associations between HPR and inflammatory markers. Conclusion: The prevalence of HPR during AAS therapy, assessed by specific methods for cyclooxygenase 1 (COX-1), is higher during the acute phase than in the late phase of NSTE ACS.

Resumo Fundamento: A alta atividade plaquetária (AAP) durante a terapia com ácido acetilsalicílico (AAS) é fator de mau prognóstico nas síndromes coronarianas agudas (SCA). A prevalência de AAP durante a SCA é maior do que a relatada na doença estável. No entanto, não está claro se esta prevalência de AAP é um fenômeno transitório ou característica dessa população de alto risco. Objetivo: O objetivo principal é comparar, em uma mesma população, os efeitos do AAS sobre a função plaquetária nas fases inicial e tardia da SCA. Os objetivos secundários são: correlação entre os testes entre si e a relação entre os testes e a variação dos marcadores inflamatórios (proteína C reativa e interleucina-6). Métodos: Foram estudados prospectivamente 70 pacientes com SCA sem elevação de ST (SCSST) em uso de 100 a 200 mg de AAS por dia por pelo menos 7 dias. A função plaquetária foi avaliada nas primeiras 48 horas e 3 meses após por quatro métodos: VerifyNow™ (VFN), agregometria de sangue total (AST) com ácido araquidônico (AA) e colágeno como agonistas, e analisador de função plaquetária (PFA). O nível de significância estatístico considerado foi < 0,05. Resultados: A média de idade foi de 65 ±9,7 anos e 54% da população eram do sexo feminino. De acordo com os métodos mais específicos (AST com AA e VFN), a incidência de AAP foi significativamente maior na fase inicial, em relação à tardia: AST com AA 31% versus 13%, p = 0,015; VFN 32% versus 16%, p = 0,049. Os outros métodos testados, menos específicos para o AAS, não mostraram diferenças significativas entre as fases. A correlação entre os métodos foi fraca ou moderada (r variando de 0,3 a 0,5, p < 0,05), e não houve associações significativas entre AAP e marcadores inflamatórios. Conclusão: A prevalência de AAP durante a terapia com AAS, avaliada por métodos específicos para cicloxigenase 1 (COX-1), é maior durante a fase aguda do que na tardia da SCASST.

The predictive effects of clinical hematological changes on saphenous graft patency after coronary artery surgery

Abstract Objectives: To investigate the association between clinical hematologic parameters and saphenous vein graft failure after on-pump coronary artery bypass surgery. Methods: A total of 1950 consecutive patients underwent isolated on-pump coronary artery surgery between November 2010 and February 2013. Of these, 284 patients met our inclusion criteria; their preoperative clinical hematological parameters were retrospectively obtained for this cohort study. And of them, 109 patients underwent conventional coronary angiography after graft failure was revealed by coronary computed tomography angiography. The primary endpoint was to catch at least one saphenous vein graft stenosis or occlusion following the coronary angiogram. We then analyzed risk factors for graft failure. In sequential or T grafts, each segment was analyzed as a separate graft. Results: In logistic regression analysis, older age, platelet distribution width, and diabetes mellitus were identified as independent predictors of saphenous vein graft failure (P<0.). In contrast, preserved ejection fraction value favored graft patency (P<0.001). Conclusion: Increased platelet distribution width is easily measurable and can be used as a simple and valuable marker in the prediction of saphenous vein graft failure.

Platelet to lymphocyte and neutrophil to lymphocyte ratios as strong predictors of mortality in intensive care population

SUMMARY OBJECTIVE: Patients in intensive care units (ICU) have greater morbidity and mortality. We aimed to study neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in the ICU population. METHODS: Medical and laboratory data of patients treated in ICU were retrospectively analyzed. Patients were divided into deceased and survived groups. RESULTS: The NLR of survived and deceased groups were 3.6 (0.2-31) and 9.5 (1-40), respectively (p<0.001). The PLR of the survived group (111 [16-537]) was significantly lower than the PLR of the deceased (209 [52-1143]), (p<0.001). An NLR higher than 4.9 had 84% sensitivity and 67% specificity is selecting deceased patients (AUC:0.80, p<0.001). A PLR higher than 112 had 83% sensitivity and 52% specificity in predicting deadly cases (AUC:0.76, p<0.001). Both PLR and NLR were significantly and positively correlated with c reactive protein levels. CONCLUSION: We suggest that physicians should pay particular attention to the treatment of patients in ICU with elevated NLR and PLR.

RESUMO OBJETIVO: Pacientes em unidades de terapia intensiva (UTI) apresentam maior morbimortalidade. Nosso objetivo foi estudar a razão de neutrófilos para linfócitos (NLR) e de plaquetas para linfócitos (PLR) na população de UTI. MÉTODOS: Dados médicos e laboratoriais dos pacientes tratados em UTI foram analisados retrospectivamente. Os pacientes foram divididos em grupos de falecidos e de sobreviventes. RESULTADOS: O NLR de indivíduos sobreviventes e falecidos foi de 3,6 (0,2-31) e 9,5 (1-40), respectivamente (p < 0,001). A PLR dos pacientes sobreviventes (111 [16-537]) foi significativamente menor do que a PLR do grupo dos falecidos (209 [52-1143]), (p < 0,001). Uma RNL maior que 4,9 teve 84% de sensibilidade e 67% de especificidade na previsão de casos mortais. (AUC: 0,80, p < 0,001). Uma PLR superior a 112 apresentou sensibilidade de 83% e especificidade de 52% na previsão de casos mortais (AUC: 0,76, p <0,001). Ambos, PLR e NLR, foram significativamente e positivamente correlacionados com os níveis de proteína reativa c. CONCLUSÃO: Sugerimos que os médicos prestem atenção especial ao tratamento de pacientes em UTI com valores elevados de RNL e RPL.

Mean platelet volume as a prognostic factor for venous thromboembolic disease / Volumen plaquetario medio como factor pronóstico de la enfermedad tromboembólica venosa

ABSTRACT Background: Mean platelet volume (MPV) is a risk factor for cardiovascular and inflammatory diseases. Aim: To evaluate the association between high MPV and 90-day mortality after an episode of venous thromboembolism (VTE). Material and Methods: Retrospective cohort of 594 patients with a median age of 73 years (58% women) with a first episode VTE, included in an institutional Thromboembolic Disease registry between 2014 and 2015. MPV values were obtained from the automated blood cell count measured at the moment of VTE diagnosis. Volumes ≥ 11 fL were classified as high. All patients were followed for 90 days to assess survival. Results: The main comorbidities were cancer in 221 patients (37%), sepsis in 172 (29%) and coronary artery disease in 107 (18%). Median MPV was 8 fl (8-9), brain natriuretic peptide 2,000 pg/ml (1,025-3,900) and troponin 40 pg/ml (19.5-75). Overall mortality was 20% (121/594) during the 90 days of follow-up. Thirty three deaths occurred within 7 days and 43 within the first month. The loss of patients from follow-up was 5% (28/594) at 90 days. Mortality among patients with high MP was 36% (23/63). The crude mortality hazard ratio (HR) for high MPV was 2.2 (95% confidence intervals (CI) 1.4-3.5). When adjusted for sepsis, oncological disease, heart disease, kidney failure and surgery, the mortality HR of high MPV was 2.4 (CI95% 1.5-3.9) in the VTE group, 2.3 (CI95% 1.5-4.4) in the deep venous thrombosis group, and 2.9 (CI95% 1.6 −5.6) in the pulmonary embolism group. Conclusions: High MPV is an independent risk factor for mortality following an episode of VTE.

Antecedentes: El volumen plaquetario medio (VPM) es un factor de riesgo de complicaciones cardiovasculares y enfermedades inflamatorias. Objetivo: Evaluar la asociación entre VPM alto y la mortalidad a los 90 días después de un episodio de tromboembolismo venoso (ETV). Material y Métodos: Cohorte retrospectiva de 594 pacientes adultos con una edad media de 73 años (58% mujeres) con un primer episodio de ETV incluidos en un registro de enfermedad tromboembólica institucional entre 2014 y 2015. Se obtuvieron valores de VPM desde el hemograma tomado en el momento del diagnóstico de ETV y un volumen ≥ 11 fL fue clasificado como alto. Todos los pacientes fueron seguidos durante 90 días para determinar sobrevida. Resultados: Las comorbilidades fueron cáncer en 221 pacientes (37%), sepsis en 172 (29%) y enfermedad coronaria en 107 (18%). La mediana de VPM fue 8 fl (89), el péptido natriurético cerebral fue de 2.000 pg/ml (1.025-3.900) y la troponina fue de 40 pg/ml (19,5-75). La mortalidad global a 90 días fue 20% (121/594). Treinta y tres muertes ocurrieron dentro de los 7 días y 43 en el primer mes. La pérdida de seguimiento de pacientes fue de 5% (28/594) a los 90 días. La mortalidad en el grupo con VPM alto fue 36% (23/63). La razón de riesgo (HR) cruda de la mortalidad para un VPM alto fue de 2,2 (intervalos de confianza (IC) de 95% 1,4-3,5). Cuando se ajustó por sepsis, enfermedad oncológica, enfermedad cardíaca, insuficiencia renal y cirugía, la HR de muerte para un VPM alto fue de 2,4 (IC95% 1,5-3,9) en el grupo de ETV; 2,3 (IC95% 1,5-4,4) en el grupo de trombosis venosa profunda; y 2,9 (CI95% 1,6 −5,6) en el grupo de embolia pulmonar. Conclusiones: Un VPM alto es un factor de riesgo independiente de mortalidad después de un episodio de ETV.

Are pre and postoperative platelet to lymphocyte ratio and neutrophil to lymphocyte ratio associated with early postoperative aki following cabg?

Abstract Objective: In this study, we investigated the role of two of the recent biomarkers of inflammation on the development of acute kidney injury in the early postoperative period of isolated coronary artery bypass grafting. Methods: Three hundred and eleven patients, who underwent isolated coronary artery bypass grafting with cardiopulmonary bypass by the same surgery team in our clinic between May 2010 and October 2014, who had a preoperative serum creatinine level lower than 1.5 mg/dl were included in the study. These patients' records were reviewed retrospectively. The diagnosis of acute kidney injury was performed according to the Kidney Disease Improving Global Outcomes 2012 Acute Kidney Injury Guideline criteria. Patients who developed acute kidney injury in the early postoperative period were classified as Group-1 (n=62) and the patients with normal postoperative renal functions were classified as Group-2 (n=249). The demographic data, body mass index, comorbidities, hematologic/biochemical profiles, preoperative ejection fraction, blood transfusion history, and operative data of the groups were compared. Univariate analyses were performed to determine significant clinical factors, and multiple logistic regression analyses were subsequently done to determine independent predictors of acute kidney injury. Results: Sixty-two (19.9%) patients developed acute kidney injury during the first 72 hours postoperatively. Multivariate logistic regression analyses revealed preoperative increased creatinine (P=0.0001), C-reactive protein (P=0.02), neutrophil-lymphocyte ratio (P=0.04) and platelet-lymphocyte ratio (P=0.002); increased postoperative first day leukocyte count (P=0.03), C-reactive protein levels (P=0.02), neutrophil-lymphocyte ratio (P=0.002), platelet-lymphocyte ratio (P=0.01) and increased intubation time (P=0.006) as independent predictors of early postoperative acute kidney injury in patients who underwent isolated coronary artery bypass grafting. Conclusion: The preoperative and postoperative increased levels of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio which can be calculated by simple methods from routine blood analysis showed us that these parameters are independent biomarkers directly related to development of acute kidney injury in the early postoperative period.

Platelet-derived growth factor A mRNA in platelets is associated with the degree of hepatic fibrosis in chronic hepatitis C

Abstract: INTRODUCTION: Transforming growth factor beta 1 (TGFB1) and platelet-derived growth factor (PDGF) are the main cytokines related to hepatic fibrogenesis. METHODS: RNA isolated from the platelets and hepatic tissue of 43 HCV carriers was used for quantitative polymerase chain reaction to determine TGFB1, PDGFA, and PDGFB RNA expression. RESULTS: The mRNA expression of PDGFA in platelets was significantly lower in the group with advanced fibrosis than in the group with early-stage fibrosis. TGFB1 was more frequently expressed in platelets than in hepatic tissue, which was different from PDGFB. CONCLUSIONS: A pathway mediated by overexpression of TGFB1 via PDGFA in megakaryocytes could be involved in the development of fibrosis.

The putative catalytic role of higher serotonin bioavailability in the clinical response to exposure and response prevention in obsessive-compulsive disorder

Objective: Exposure and response prevention (ERP) is effective to treat obsessive-compulsive disorder (OCD), but the lack of tolerance to the aversion nature of exposure techniques results in a high drop-out rate. There have been reports of a generic stress endurance effect of serotonin (5-HT) in the central nervous system (CNS) which might be explained by suppression of defensive fixed action patterns. Previous studies have proposed that higher baseline 5-HT concentration and slow decrease in concentration during drug treatment of OCD were predictors of good clinical response to 5-HT reuptake inhibitors. The objective of this study was to investigate whether pre-treatment platelet rich plasma (PRP) 5-HT concentration is associated with latency of treatment response and final response to an ERP protocol for obsessive-compulsive disorder (OCD). Methods: Thirty adult and treatment-free OCD patients were included in an 8-week, 16-session ERP protocol. 5-HT concentration was determined at baseline and after treatment. Patients with a reduction ≥30% on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at the end of ERP were defined as responders. Results: A positive correlation between baseline 5-HT concentration and reduction of symptoms on the Y-BOCS was observed after 4 weeks. Baseline 5-HT concentration was not correlated with clinical response after 8 weeks of ERP, possibly due to the similar though delayed clinical response of patients with lower (compared to those with higher) baseline 5-HT concentration. Patients with higher 5-HT baseline concentration also showed more improvement in depressive symptoms with treatment. Conclusion: The present results partially support the hypothesis of a stress endurance effect of 5-HT in OCD patients. According to the literature, fast onset responders possibly have more or larger 5-HT containing neurons, higher endogenous 5-HT synthesis or lower monoamine oxidase activity; all these hypotheses remain to be investigated.

Efecto del 27- hidroxicolesterol en la acción antiplaquetaria de estradiol en mujeres postmenopáusicas / 27- Hydroxycholesterol reverses estradiol induced inhibition of platelet aggregation in postmenopausal women

Background: The decline of estrogen levels increases cardiovascular risk in women. Platelets express estrogen receptors and 17β-estradiol- (E2) can produce a protective effect on thrombus formation. The hydroxylation of cholesterol generates several sterols and 27-hydroxycholesterol (27HC) predominates in circulation. Aim: To evaluate the effect of 27HC as an endogenous antagonist of the anti-aggregating properties of E2 in platelets of postmenopausal women. Material and Methods: Platelet function of postmenopausal women was evaluated ex-vivo. Platelets pre-incubated with 27HC in the presence or absence of E2, were stimulated with collagen. Aggregation was evaluated using turbidimetry using a Chrono-log aggregometer. Results: Collagen-stimulated platelet aggregation was significantly inhibited by E2. The inhibitory effect of E2 on collagen-stimulated platelet aggregation was significantly reversed in the presence of 27HC. Conclusions: The suppressive effect of E2 on platelet aggregation is inhibited by 27HC, which could contribute to increase cardiovascular risk in postmenopausal women.

O volume plaquetário médio abaixo do normal está associado com extensão reduzida de doença arterial coronariana / Lower than normal mean platelet volume is associated with reduced extent of coronary artery disease

FUNDAMENTO: A extensão da doença arterial coronariana aterosclerótica em pacientes com angina estável tem importantes implicações prognósticas e terapêuticas. Em modelos atuais de evolução de placas, os trombócitos desempenham um papel importante no crescimento de placas. O volume plaquetário médio é um marcador facilmente determinado, com evidência de correlação com a agregabilidade plaquetária in vitro, além de valores comprovadamente maiores após eventos vasculares agudos. OBJETIVO: No presente estudo, investigou-se a relação entre o volume plaquetário médio e a extensão angiográfica da doença arterial coronariana em pacientes com angina estável. MÉTODOS: Foram analisados prontuários, hemograma completo e dados angiográficos anteriores de 267 pacientes elegíveis com angina estável. A extensão angiográfica da doença arterial coronariana foi avaliada à luz de dados angiográficos, com o uso por um especialista do escore de Gensini em uma cardiologia invasiva. Os valores para o volume plaquetário médio foram obtidos a partir de hemogramas completos, obtidos um dia antes da angiografia. Com relação ao intervalo populacional para o volume plaquetário médio, os pacientes foram agrupados dentro (n = 176) e abaixo (n = 62) do referido intervalo. Foi realizada uma comparação entre grupos e uma análise correlacional. RESULTADOS: Não houve correlação linear entre o escore de Gensini total e o volume plaquetário médio (p = 0,29), ao passo que a contagem total de trombócitos apresentou correlação inversa com o volume plaquetário médio (p < 0,001, r = 0,41). Os pacientes com volume plaquetário médio abaixo do normal apresentaram um escore de Gensini (36,73 ± 32,5 vs. 45,63 ± 32,63; p = 0,023) e doença coronariana triarterial (18% VS. 36%; p = 0,007) significativamente inferiores se comparados com aqueles apresentando valores de volume plaquetário médio dentro dos intervalos populacionais. CONCLUSÃO: Nossas constatações não demonstraram nenhuma relação linear entre o volume plaquetário médio e a extensão da doença arterial coronariana, ao passo que os pacientes com volume plaquetário médio abaixo do normal apresentaram uma extensão reduzida da doença arterial coronariana.

BACKGROUND: Extent of atherosclerotic coronary artery disease in patients with stable angina has important prognostic and therapeutic implications. In current models of plaque evolution, thrombocytes play an important role in plaque growth. Mean platelet volume is a readily obtainable marker that was shown to correlate with platelet aggregability in vitro and increased values were demonstrated after acute vascular events. OBJECTIVE: In this study, we investigated the relationship of mean platelet volume and angiographic extent of coronary artery disease in patients with stable angina. METHODS: Past medical records, complete blood count and angiographic data of 267 eligible stable angina patients were reviewed. Angiographic extent of coronary artery disease was evaluated form angiographic data using Gensini score by an expert in invasive cardiology. Mean platelet volume values were obtained from complete blood counts that obtained one day before angiography. Patients were grouped as those within (n = 176) and lower than (n = 62) population-based range for mean platelet volume. Comparison between groups and correlation analysis was performed. RESULTS: There were no linear correlation between total Gensini score and mean platelet volume (p = 0.29), while total thrombocyte count was inversely correlated with mean platelet volume (p < 0.001; r = 0.41). Patients with lower than normal mean platelet volume had significantly lower Gensini score (36.73 ± 32.5 vs. 45.63 ± 32.63; p = 0.023) and three-vessel disease (18% vs. 36%; p = 0.007) compared with those mean platelet volume values within population-based ranges. CONCLUSION: Our findings show no linear relationship exists between mean platelet volume and extent of coronary artery disease, while patients with lower than normal mean platelet volume had reduced extent of coronary artery disease.

Mecanismos moleculares e celulares envolvidos na modulação da via L-arginina-óxido nítrico em hipertensão e insuficiência renal crônica / Molecular and cellular mechanisms involved in modulation of L-arginine-nitric oxide in hypertension and chronic renal failure

A Insuficiência renal crônica (IRC) e a hipertensão arterial sistêmica (HAS) são patologias com alta morbidade e mortalidade, consumindo grandes verbas de saúde pública. A disfunção endotelial presente tanto na IRC, como na hipertensão, contribui para a manutenção de elevada resistência periférica, favorecendo complicações como a aterosclerose. Esta disfunção endotelial é parte de um estado pró-trombótico, levando à ocorrência de eventos cardiovasculares, principal causa de morte nestas patologias. O óxido nítrico (NO) tem um papel importante na modulação da atividade plaquetária. Anormalidades na síntese e/ou inativação do NO são descritas tanto na insuficiência renal crônica como na hipertensão. Estudos prévios demonstraram uma redução do influxo de L-arginina em eritrócitos e plaquetas de pacientes hipertensos e em um modelo animal de hipertensão. Além disso, em IRC, nosso grupo mostrou uma ativação da via L-arginina-NO em plaquetas. O objetivo dessa tese é avaliar a via L-arginina-NO na HAS e em diferentes estágios de IRC, bem como investigar o ciclo da uréia, e a presença de marcadores de estresse nesses pacientes. De acordo com o presente estudo pôde-se verificar que não houve alteração na síntese de NO em eritrócitos na hipertensão, todavia ocorre uma ativação do ciclo da uréia, que pode ser dada pelo aumento do influxo de L-arginina eritrocitário previamente demonstrado. Não foi demonstrada diferença significativa na peroxidação lipídica sistêmica, em plaquetas ou eritrócitos na HAS. Em plaquetas, no entanto, houve uma redução da atividade da NO sintase (NOS), que não foi acompanhada por alteração da expressão das isoformas da NOS, da arginase, da fosfodiesterase 5 (PDE5) ou da guanilato ciclase (GC) solúvel. Essa redução na síntese de NO em plaquetas pode ser explicada por um menor influxo de L-arginina que está presente na hipertensão. Os eritrócitos de pacientes renais crônicos em hemodiálise mostraram um maior influxo de L-arginina...

Chronic renal failure (CRF) and essential hypertension (EH) are diseases associated with high rates of morbidity and mortality, consuming huge amounts of money from the public health system. The endothelial dysfunction existent in both diseases, CRF and EH, contributes to the maintenance of the high peripheral resistance, and contribute to circulatory complications such as atherosclerosis. This endothelial dysfunction is part of a pro-thrombotic state, leading to cardiovascular events, which are the major cause of death in these disorders. Nitric oxide (NO) plays an important role in the modulation of platelet function. Abnormalities of NO synthesis or inactivation are described in CRF and EH. It was previously reported an inhibition of L-arginine transport in erythrocytes of hypertensive patients and in an animal model of hypertension. Moreover, we have also demonstrated an activation of L-arginine-NO pathway in platelets taken from uraemic patients. The aim of the present thesis is to investigate L-arginine-NO pathway in arterial hypertension and in different stages of chronic renal failure. It will also be evaluated urea cycle and the presence of oxidative stress markers in these patients. According to the present study it was not detected any alteration in erythrocytes NO synthesis in hypertension, however, there was an activation of urea cycle, which could be explained by an increase in L-arginine influx. The present study has not demonstrated significative difference in markers of lipid peroxidation in the serum, platelets or erythrocytes in hypertension. In platelets however, there was an inhibition of NO synthase (NOS) activity without any alterations of NOS isoforms, arginase, phosphodiesterase 5 (PDE5) or soluble guanylyl cyclase (sGC) expression. This reduction of NO synthesis may be explained by a lower influx of L-arginine that is present on hypertension. Erythrocytes from chronic renal failure patients under haemodyalysis...

O papel do RDW, da morfologia eritrocitária e de parâmetros plaquetários na diferenciação entre anemias microcíticas e hipocrômicas / The role of RDW, erythrocyte morphology and platelet parameters in the differentiation between microcytic and hypochromic anemias

As anemias microcíticas e hipocrômicas atingem grande parcela da população mundial. Entre estas, significativa porcentagem de casos se deve à deficiência do ferro, enquanto em algumas regiões a frequência de talassemia menor se torna importante. Por outro lado, a anemia de doença crônica é a causa mais comum de anemia em pacientes hospitalizados. O diagnóstico diferencial destas doenças é clinicamente importante, e é atualmente realizado através dos exames padrão ouro envolvendo a avaliação do metabolismo do ferro e dosagem de HbA2. Embora dotados de grande utilidade, estes testes podem apresentar uma metodologia mais demorada e onerosa que, em casos de concomitância de doenças, comuns na prática clínica, não conseguem proporcionar um correto diagnóstico. Na tentativa de otimizar e direcionar o diagnóstico destas anemias, o uso de alguns parâmetros derivados dos modernos contadores automáticos tem sido sugerido. Neste estudo, o papel do RDW, parâmetros plaquetários (número de plaquetas, PDW, VPM) e morfologia eritrocitária como parâmetros diferenciadores, foi avaliado em um grupo de 159 pacientes portadores de anemia microcítica e hipocrômica devido à deficiência do ferro, anemia de doença crônica e talassemia beta menor, comprovado pelos exames padrão ouro. Foi possível observar que o RDW não se mostrou um bom discriminante, enquanto o índice plaquetário PDW pode ser um parâmetro auxiliar no diagnóstico diferencial das anemias microcíticas e hipocrômicas. Com relação às alterações morfológicas dos eritrócitos, o pontilhado basófilo foi um achado bastante comum apenas em pacientes portadores de talassemia beta menor, com indícios de potencial utilidade na elucidação de casos de microcitose.

Microcytic and hypochromic anemias affect many people worldwide. A significant percentage of cases are due to iron deficiency, while in certain regions the frequency of thalassemia minor is important. On the other hand, anemia of chronic disease is the most common cause of anemia in hospitalized patients. Differential diagnosis between these anemias, currently established by using gold standard tests involving evaluation of iron metabolism and measurement of HbA2, is of clinical importance. Although very useful, these tests are time consuming and onerous. In cases of concomitant diseases, a common finding in the clinical practice, these tests are unable to provide a correct diagnosis. In an attempt to optimize diagnosis of these anemias, the use of some parameters derived from modern automated blood count analyzers has been suggested. In this study, the role of RDW, platelet parameters (platelet number, PDW, MPV) and erythrocyte morphology as differentiating parameters were evaluated in a group of 159 patients diagnosed as carriers of microcytic or hypochromic anemias due to iron deficiency, anemia of chronic disease and â-thalassemia minor, as confirmed by gold standard tests. The RDW did not prove to be a good discriminator, while the platelet index, PDW, may be helpful in the differential diagnosis of microcytic and hypochromic anemias. Regarding the red cell morphologic alterations, basophilic stippling was a quite common finding just in patients with â-thalassemia minor, suggesting it to be a potential marker for elucidating cases of microcytosis.

Valores de agregabilidad plaquetaria anormales en una población diabética con respecto a una población sana / Value of plaleted adnormals in diabetic population with respect an curative population

Las enfermedades cardiovasculares (ECV) son causantes de mayor morbilidad y mortalidad que cualquier otra categoría de enfermedad humana en el mundo. Según la Organización Mundial de la Salud, para el 2020 más del 40 por ciento de la mortalidad total estará relacionada a la ECV. En este sentido la evaluación en diversas condiciones pretrombóticas, como diabetes mellitus o hiperlipidemia, y en trombosis establecida, han sido detectadas anormalidades de la agregación plaquetaria, bien sea espontánea, in vitro como adición de agentes agregantes o inferida por la cantidad de microagregados plaquetarios circulantes. Este trabajo fue conducido con la finalidad de establecer una comparación entre los valores de agregabilidad plaquetaria en una población normal y una población diabética. Fueron estudiados 22 sujetos sanos y 20 pacientes con diabetes mellitus, no fumadores con edad comprendida entre 18 y 48 años de ambos sexos los cuales acudían en condiciones de ayunas, de 14 horas, a c/u de estos se les realizó la extracción de sangre, para la agregación plaquetaria. Para la obtención de plasma rico en plaquetas, las muestras se centrifugaron a 970 r.p.m x 10 minutos. APD, colágeno y epinefrina de Sigma Diagnostics fueron utilizados como promotores de la agregabilidad plaquetaria y medidos en el Agregómetro de la Chrono Log, el cual registra nefelométricamente cambios de turbidez y son inmediatamente transmitidos a un registrador directamente acoplado al anterior. Los resultados obtenidos fueron los siguientes: en los individuos sanos el contaje plaquetario fue 269,61ñ 52,37 plaquetas /cmü y en cuanto a la agregación plaquetaria con ADP 72,32ñ 13,42 colágeno 74,63ñ 14,20 y epinefrina 69,90ñ 14,58, y en los pacientes diabéticos con ADP, 80,53ñ 15,86, colágeno 84,22ñ 14,08 y epinefrina 77,62ñ 12,45, estos fueron los valores encontrados. Pudimos observar que los valores de agregación plaquetaria fueron mayores en las muestras de los pacientes diabéticos en comparación con los individuos sanos, con lo cual podríamos decir que estas determinaciones como ADP, colágeno y epidefrina nos pueden servir de iniciativo como un factor más riesgo en pacientes con diabetes mellitus, o en pacientes de alto riesgo para enfemedades cardiovasculares