RESUMO
INTRODUCTION: Community acquired pneumonia (CAP) is a major cause of morbidity and mortality. While there is much data about risk factors for severe outcome in the general population, there is less focus on younger group of patients. Therefore, we aimed to detect simple prognostic factors for severe morbidity and mortality in young patients with CAP. METHODS: Patients of 60 years old or younger, who were diagnosed with CAP (defined as pneumonia identified 48 hours or less from hospitalization) between March 1, 2005 and December 31, 2008 were retrospectively analyzed for risk factors for complicated hospitalization and 90-day mortality. RESULTS: The cohort included 637 patients. 90-day mortality rate was 6.6% and the median length of stay was 5 days. In univariate analysis, male patients and those with co-morbid conditions tended to have complicated disease. In multivariate analysis, variables associated with complicated hospitalization included post chest radiation state, prior neurologic damage, blood urea nitrogen (BUN) > 10.7 mmol/L and red cell distribution width (RDW) > 14.5%; whereas, variables associated with an increased risk of 90-day mortality included age ≥ 51 years, prior neurologic damage, immunosuppression, and the combination of abnormal white blood cells (WBC) and elevated RDW. Complicated hospitalization and mortality rate were significantly higher among patients with increased RDW regardless of the white blood cell count. Elevated RDW was associated with a significant increase in complicated hospitalization and 90-day mortality rates irrespective to hemoglobin levels. CONCLUSIONS: In young patients with CAP, elevated RDW levels are associated with significantly higher rates of mortality and severe morbidity. RDW as a prognostic marker was unrelated with hemoglobin levels. TRIAL REGISTRATION: ClinicalTrials.Gov NCT00845312.
Assuntos
Infecção Hospitalar/sangue , Índices de Eritrócitos , Eritrócitos/fisiologia , Avaliação de Resultados em Cuidados de Saúde , Pneumonia/sangue , Pneumonia/mortalidade , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Heparanase that was cloned from and is abundant in the placenta is implicated in cell invasion, tumor metastasis and angiogenesis. Recently, we demonstrated that heparanase is directly involved in the regulation of the hemostatic system. Heparanase was shown to form a complex and enhance tissue factor (TF) activity, resulting in increased factor Xa production (Nadir et al. Haematologica, 2010). The present work suggests a novel assay to evaluate heparanase procoagulant activity. METHODS: Heparanase procoagulant activity was studied using purified proteins of heparanase, TF, factor VIIa and factor X. The assay was verified in 55 plasma samples and compared to heparanase and tissue factor pathway inhibitor (TFPI) levels by ELISA and factor Xa, thrombin levels and antithrombin activity by chromogenic substrates. Thirty five samples were of third-trimester pregnant women (weeks 36-41) who were in labor or came for appointed elective cesarean section and 20 control samples were of non-pregnant healthy women. RESULTS: Heparanase procoagulant activity assay was shown to differentiate heparanase procoagulant effect from TF activity, in purified proteins. Heparanase procoagulant activity was significantly higher in the plasma of pregnant women compared to non-pregnant (p < 0.005). Heparanase relative contribution to the TF / heparanase complex activity was significantly higher in the plasma of pregnant women compared to non-pregnant (29% increase, p < 0.0001). Differences in heparanase procoagulant activity were more prominent than changes in heparanase levels by ELISA, TF activity, factor Xa, thrombin and free TFPI levels. CONCLUSIONS: Heparanase procoagulant activity can be determined by the suggested assay. The assay revealed a significant contribution of heparanase to the procoagulant state in late third-trimester pregnancy and at delivery.
Assuntos
Testes de Coagulação Sanguínea , Coagulação Sanguínea , Glucuronidase/sangue , Placenta/enzimologia , Antitrombinas/sangue , Estudos de Casos e Controles , Cesárea , Procedimentos Cirúrgicos Eletivos , Ensaio de Imunoadsorção Enzimática , Fator VIIa/metabolismo , Fator X/metabolismo , Feminino , Humanos , Israel , Lipoproteínas/sangue , Gravidez , Terceiro Trimestre da Gravidez/sangue , Trombina/metabolismo , Tromboplastina/metabolismo , Regulação para CimaRESUMO
BACKGROUND: Heparanase is an endo-ß-D-glucuronidase dominantly involved in cell invasion, tumor angiogenesis and metastasis. Recently, we demonstrated increased levels of heparanase, tissue factor pathway inhibitor (TFPI)-2 and vascular endothelial growth factor (VEGF)-A in early miscarriages (Nadir et al., Thromb Res, 2010). Herein, we investigated the role of heparanase in third trimester placentas, in correlation to tissue factor (TF), TFPI, TFPI-2, and VEGF-A. METHODS: Twenty five third-trimester placenta samples (weeks 36-41) were studied applying real time RTPCR and immunostaining. Ten cases were placentas of elective cesarean sections, 8 cases were of normal vaginal deliveries and 7 samples were placentas of intra-uterine growth restriction (IUGR) fetuses. Skin and lung tissues of heparanase over-expressing mice and heparanase knock-out mice were subjected to immunostaining. RESULTS: Sections obtained from vaginal and IUGR placentas revealed 2 folds increased levels of heparanase, TFPI-2 and VEGF-A compared to placentas from elective cesarean sections in maternal decidua as well as in fetal placenta elements. Interestingly, abundance of TFPI staining in the intra-villous blood was observed in placentas of vaginal and IUGR deliveries. Heparanase effect on TFPI release to the blood was supported by immunostaining of heparanase over-expressing and heparanase knock-out mice tissues. CONCLUSIONS: In regard to our previous data on early pregnancy losses, the present data strengthen the understanding that in placental vascular complications levels of heparanase, TFPI-2 and VEGF-A increase. In the process of delivery, heparanase may have a regulatory role on TFPI release to fetal circulation.