No abstract

The role played by hemorheological alterations in the development of deep vein thrombosis (DVT) has often been overlooked. Although marked rheological alterations and the relationship with thromboembolic events are well-defined in patients with hematological diseases such as myelom, Waldenström disease and polycythemia vera, the relationship is not so clear in patients without hematological diseases. In the present review, we analyzed studies evaluating the rheological profile in DVT patients. Among the cardiovascular risk factors, only hyperlipidemia, metabolic syndrome, tobacco and obesity increase DVT risk and, in addition, a disturbed rheological profile is shown which could further increase this risk. The significance of hematocrit and fibrinogen, the main factors influencing blood viscosity, is not sufficient to increase blood viscosity in any of the studies analyzed. DVT patients show increased fibrinogen levels and erythrocyte aggregation throughout all the studies despite patients not being in an acute reactant phase.In addition to rheological alterations, it is necessary to consider local conditions at pockets of venous valves which undergo deterioration with aging and play an important role equally to alterations in the rheological profile. Moreover, it is necessary to take into account that systemic rheological alterations are not comparable to those in low shear rate areas where minimum disturbances could be more relevant.It would be convenient to perform multicentric studies with the same rheological methodology and pre-analytical procedures to evaluate, in order to obviate the effect of thrombophilic and circumstantial risk factors, rheological parameters in patients with spontaneous DVT to elucidate their real contribution to the development of thromboembolic events.

Increased red blood distribution width (RDW) in anemia is related to disturbances in the cellular surface/volume ratio, usually accompanied by morphological alterations, while it has been shown in inflammatory diseases that the activity of pro-inflammatory cytokines disturbing erythropoiesis increases RDW. Recently it has been reported that higher RDW is related with decreased erythrocyte deformability, and that it could be related with the association of RDW and increased risk of cardiovascular diseases. In order to analyze the influence of morphological alterations and proinflammatory status on the relationship between RDW and erythrocyte deformability, we analyzed erythrocyte deformability along with RDW and other hematological and biochemical parameters in 36 α-thalassemia, 20 β-thalassemia, 20 δβ-thalassemia trait carriers, 61 metabolic syndrome patients and 76 morbidly obese patients. RDW correlated inversely with erythrocyte deformability in minor β-thalassemia (r =-0.530, p < 0.05), and directly in both metabolic syndrome and morbidly obese patients (ρ= 0.270, p < 0.05 and ρ= 0.258, p < 0.05, respectively). Minor β-thalassemia is often accompanied by more marked cell-shaped perturbations than other thalassemia traits. This could be the reason for this negative association only in this setting. Higher anisocytosis seems to be associated with greater morphologic alterations (shape/volume), which reduce erythrocyte deformability. The proinflammatory profile in metabolic patients can be related to the positive association of RDW with erythrocyte deformability found in these patients. However, further research is needed to explain the mechanisms underlying this association.

Increased RDW has been found to be a marker of adverse outcomes in cardiovascular disease (CVD), although the exact mechanism remains unclear.Recently, several authors have found that higher RDW is associated with decreased erythrocyte deformability, which can impair blood flow through microcirculation, a fact which may explain the increased risk for CVD events associated with elevated RDW.The aim of the present study was to investigate the association between RDW and erythrocyte deformability in patients with acute myocardial infarction (AMI).The study group comprised 60 AMI patients and 72 gender-and age-matched controls, in whom erythrocyte deformability was determined by means of the elongation index (EI) in a Rheodyn SSD, along with haematological, biochemical and inflammatory parameters.Patients showed higher RDW (p = 0.012) and lower EI (p < 0.05) than controls. When anaemic patients were removed from the study, AMI showed still lower EI than controls (p < 0.05), but no differences in RDW were observed (p = 0.141).RDW correlated inversely with haematimetric indices (p < 0.001), but not with inflammatory and biochemical parameters (p > 0.05). EI correlated inversely with Hb, MCHC (p < 0.001) and directly with MCV (p < 0.05). EI also correlated inversely with glucose (p < 0.05) and directly with HDL-cholesterol (p < 0.05). The multivariate regression model showed that only MCV and Hb were independent predictors of RDW (beta coefficients: −0.383, −0.208; p < 0.001, p = 0.050, respectively). In addition, MCV, MCHC and hyperlipidaemia were independent predictors of EI (beta coefficients: 0.366, −0.533, −0.192; p < 0.001, p < 0.001, p = 0.019 respectively).In AMI patients, increased RDW is not related with EI, so this mechanism does not seem to be responsible for an increased CDV risk in these patients.

Rationale: A depressed expression of antigen presentation is, along with endothelial dysfunction, a recognized signature of severe community-acquired pneumonia (CAP). We aimed to evaluate the expression of a number of genes involved in the immunological synapse in non-critically ill CAP patients with or without organ dysfunction and to profile endothelial biomarkers such as proendothelin-1 (proET1) and proadrenomedullin (proADM). Methods: A nested study in a prospective cohort in CAP patients was performed. Expression levels of major histocompatibility complex class II DR alpha (HLA-DRA), CD40 ligand (CD40LG), CD3E, CD28, and inducible T-cell costimulator (ICOS) were quantified by using droplet digital polymerase chain reaction and endothelial biomarkers by immunofluorescence. Results: Ninety-four patients were included, 44.7% of whom had organ failure in one or more organs. A significant decrease in the expression of the five genes with increased levels of proadrenomedullin (proADM) and proendothelin-1 (proET1) was found in CAP with organ failure. The depressed expression of HLA-DRA (odds ratio (OR), 2.94), CD40LG (OR, 3.90), and CD28 (OR, 3.48) was independently associated with organ failure after adjustment for age, Charlson score, and severity. Conclusions. CAP with organ failure showed depressed expression of immunological synapse genes with increased levels of biomarkers denoting endothelial damage. Simultaneous profiling of immunological and endothelial signatures could help in the early identification of organ failure in CAP and in the implementation of personalized treatment.