Tissue factor and nitric oxide: A controversial relationship! (review)

Tissue factor (TF) is the primary physiological initiator of blood coagulation. TF has a high-affinity for factor (F) VII resulting in the formation of (TF:FVII:FVIIa) bimolecular complex which, in the presence of Ca2+, increases the enzymatic activity of FVIIa towards its natural substrates, FIX and FX, generating their active forms FIXa and FXa, respectively. This eventually leads to thrombin generation and a fibrin clot formation. Up-regulation of TF in injured blood vessels and atherosclerotic plaque can lead to undesirable vascular thrombosis. Nitric oxide (NO) is a free radical synthesized from L-arginine and molecular oxygen by nitric oxide synthases (NOS). NO participates in diverse physiological and pathophysiological process as an intra or extracellular messenger. A relationship between TF and NO has been proposed. Thus, models of TF regulation by NO has been studied in different cells and experimental animal models, but the results have been conflicting. The premise that NO donors can prevent TF expression in vivo has provided the foundation for a broad field of pharmacotherapeutics in vascular medicine. A new class of drugs combining a statin (inhibitors of coenzyme A reductase) with an NO-donating moiety has been described. The resulting drug, nitrostatin, has been suggested to increase the antithrombotic effects of native statin. However, it is questionable if NO release from these drugs had any significant role on TF inhibition. In summary, care must be taken in drawing conclusions about the relationship between NO and TF. Interpretation of NO studies must take several factors into consideration, including NO bioavailability, its half-life and inactivation, as well as the cell type and experimental model use

Hemostatic Parameters according to Renal Function and Time after Transplantation in Brazilian Renal Transplanted Patients

Kidney transplantation is the key for patients with end-stage renal disease, improving quality of life and longer survival. However, kidney transplant triggers an intense inflammatory response and alters the hemostatic system, but the pathophysiological mechanisms of these changes are not completely understood. The aim of this cross-sectional cohort study was to investigate hemostatic biomarkers in Brazilian renal transplanted patients according to renal function and time after transplantation. A total of 159 renal transplanted patients were enrolled and D-Dimer (D-Di), Thrombomodulin (TM), von Willebrand Factor (VWF), and ADAMTS13 plasma levels were assessed by ELISA. An increase of D-Di was observed in patients with higher levels of creatinine. ADAMTS13 levels were associated with creatinine plasma levels and D-Di levels with Glomerular Filtration Rate. These results suggested that D-Di and ADAMTS13 can be promising markers to estimate renal function. ADAMTS13 should be investigated throughout the posttransplant time to clarify the participation of this enzyme in glomerular filtration and acceptance or rejection of the graft in Brazilian transplanted patients

Antiagregantes plaquetários na prevenção primária e secundária de eventos aterotrombóticos

A aterotrombose e suas complicações correspondem, hoje, à principal causa de mortalidade no mundo todo, e sua incidência encontra-se em franca expansão. As plaquetas desempenham um papel essencial na patogênese dos eventos aterotrombóticos, justificando a utilização dos antiagregantes plaquetários na prevenção dos mesmos. Desse modo, é essencial que se conheça o perfil de eficácia e segurança desses fármacos em prevenção primária e secundária de eventos aterotrombóticos. Dentro desse contexto, a presente revisão foi realizada com o objetivo de descrever e sintetizar os resultados dos principais ensaios, envolvendo a utilização de antiagregantes nos dois níveis de prevenção, e avaliando a eficácia e os principais eventos adversos relacionados à terapia

Economy class syndrome: what is it and who are the individuals at risk?

Abstract The term 'economy class syndrome' refers to the occurrence of thrombotic events during long-haul flights that mainly occur in passengers in the economy class of the aircraft. This syndrome results from several factors related to the aircraft cabin (immobilization, hypobaric hypoxia and low humidity) and the passenger (body mass index, thrombophilia, oral contraceptives or hormone replacement therapy, cancer), acting together to predispose to excessive blood coagulation, which can result in venous thromboembolism. Several risk factors, both genetic and acquired, are associated with venous thromboembolism. The most important genetic risk factors are natural anticoagulant deficiencies (antithrombin, protein C and protein S), factor V Leiden, prothrombin and fibrinogen gene mutations and non-O blood group individuals. Acquired risk factors include age, pregnancy, surgery, obesity, cancer, hormonal contraceptives and hormone replacement therapy, antiphospholipid syndrome, infections, immobilization and smoking. People who have these risk factors are predisposed to hypercoagulability and are more susceptible to suffer venous thromboembolism during air travel. For these individuals, a suitable outfit for the trip, frequent walks, calf muscle exercises, elastic compression stockings and hydration are important preventive measures. Hence, it is essential to inform about economic class syndrome in an attempt to encourage Brazilian health and transport authorities to adopt measures, in partnership with the pharmaceutical industry, to prevent venous thromboembolism

Hemostatic changes in patients with chronic renal failure undergoing haemodialysis

Patients undergoing hemodialysis may show both thrombotic complications and bleeding abnormalities. Hemostatic changes in patients on hemodialysis may result from alterations in vessel wall integrity and platelet function, and reduced blood flow in the native arteriovenous fistula. Vascular complications represent 20-25% of all hospitalizations of patients on hemodialysis. Literature survey revealed that changes in the hemostatic system may play a major role in vascular complications observed in these patients. Thus, it is essential to investigate hemostatic alterations in patients on hemodialysis so that adequate regimes for anticoagulant therapy could be implemented. In this review we discuss hemostatic abnormalities in end stage renal disease patients undergoing hemodialysi

Dangerous universal donors: the reality of the Hemocentro in Belo Horizonte, Minas Gerais

ABSTRACT BACKGROUND: The term dangerous universal blood donor refers to potential agglutination of the erythrocytes of non-O recipients due to plasma of an O blood group donor, which contains high titers of anti-A and/or anti-B hemagglutinins. Thus, prior titration of anti-A and anti-B hemagglutinins is recommended to prevent transfusion reactions. OBJECTIVE: The aim of this study was to estimate the frequency of dangerous universal donors in the blood bank of Belo Horizonte (Fundação Central de Imuno-Hematologia - Fundação Hemominas - Minas Gerais) by determining the titers of anti-A and anti-B hemagglutinins in O blood group donors. METHOD: A total of 400 O blood group donors were randomly selected, from March 2014 to January 2015. The titers of anti-A and anti-B hemagglutinins (IgM and IgG classes) were obtained using the tube titration technique. Dangerous donors were those whose titers of anti-A or anti-B IgM were ≥128 and/or the titers of anti-A or anti-B IgG were ≥256. Donors were characterized according to gender, age and ethnicity. The hemagglutinins were characterized by specificity (anti-A and anti-B) and antibody class (IgG and IgM). RESULTS: Almost one-third (30.5%) of the O blood group donors were universal dangerous. The frequency among women was higher than that of men (p-value = 0.019; odds ratio: 1.66; 95% confidence interval: 1.08-2.56) and among young donors (18-29 years old) it was higher than for donors between 49 and 59 years old (p-value = 0.015; odds ratio: 3.05; 95% confidence interval: 1.22-7.69). There was no significant association between dangerous universal donors and ethnicity, agglutinin specificity or antibody class. CONCLUSION: Especially platelet concentrates obtained by apheresis (that contain a substantial volume of plasma), coming from dangerous universal donors should be transfused in isogroup recipients whenever possible in order to prevent the occurrence of transfusion reactions

Hemostatic Parameters according to Renal Function and Time after Transplantation in Brazilian Renal Transplanted Patients

Kidney transplantation is the key for patients with end-stage renal disease, improving quality of life and longer survival. However, kidney transplant triggers an intense inflammatory response and alters the hemostatic system, but the pathophysiological mechanisms of these changes are not completely understood. The aim of this cross-sectional cohort study was to investigate hemostatic biomarkers in Brazilian renal transplanted patients according to renal function and time after transplantation. A total of 159 renal transplanted patients were enrolled and D-Dimer (D-Di), Thrombomodulin (TM), von Willebrand Factor (VWF), and ADAMTS13 plasma levels were assessed by ELISA. An increase of D-Di was observed in patients with higher levels of creatinine. ADAMTS13 levels were associated with creatinine plasma levels and D-Di levels with Glomerular Filtration Rate. These results suggested that D-Di and ADAMTS13 can be promising markers to estimate renal function. ADAMTS13 should be investigated throughout the posttransplant time to clarify the participation of this enzyme in glomerular filtration and acceptance or rejection of the graft in Brazilian transplanted patients

Influence of ACE I/D Polymorphism on Circulating Levels of Plasminogen Activator Inhibitor 1, D-Dimer, Ultrasensitive C-Reactive Protein and Transforming Growth Factor β1 in Patients Undergoing Hemodialysis.

BACKGROUND:There is substantial evidence that chronic renal and cardiovascular diseases are associated with coagulation disorders, endothelial dysfunction, inflammation and fibrosis. Angiotensin-Converting Enzyme Insertion/Deletion polymorphism (ACE I/D polymorphism) has also be linked to cardiovascular diseases. Therefore, this study aimed to compare plasma levels of ultrassensible C-reactive protein (usCRP), PAI-1, D-dimer and TGF-β1 in patients undergoing HD with different ACE I/D polymorphisms. METHODS:The study was performed in 138 patients at ESRD under hemodialysis therapy for more than six months. The patients were divided into three groups according to the genotype. Genomic DNA was extracted from blood cells (leukocytes). ACE I/D polymorphism was investigated by single polymerase chain reaction (PCR). Plasma levels of D-dimer, PAI-1 and TGF-β1 were measured by enzyme-linked immunosorbent assay (ELISA), and the determination of plasma levels of usCRP was performed by immunonephelometry. Data were analyzed by the software SigmaStat 2.03. RESULTS:Clinical characteristics were similar in patients with these three ACE I/D polymorphisms, except for interdialytic weight gain. I allele could be associated with higher interdialytic weight gain (P = 0.017). Patients genotyped as DD and as ID had significantly higher levels of PAI-1 than those with II genotype. Other laboratory parameters did not significantly differ among the three subgroups (P = 0.033). Despite not reaching statistical significance, plasma levels of usCRP were higher in patients carrying the D allele. CONCLUSION:ACE I/D polymorphisms could be associated with changes in the regulation of sodium, fibrinolytic system, and possibly, inflammation. Our data showed that high levels of PAI-1 are detected when D allele is present, whereas greater interdialytic gain is associated with the presence of I allele. However, further studies with different experimental designs are necessary to elucidate the mechanisms involved in these associations