Background: Folate and vitamin B12 are essential nutrients, whose deficiencies are considerable public health problems worldwide, affecting all age groups. Low levels of these vitamins have been associated with high concentrations of homocysteine (Hcy) and can lead to health complications. Several genetic polymorphisms affect the metabolism of these vitamins. The aims of this study were to assess folate, vitamin B12 and homocysteine status in distinct Brazilian individuals after the initiation of folic acid fortification by Brazilian authorities and to investigate the effects of RFC1 A80G, GCPII C1561T and MTHFR C677T polymorphisms on folate, vitamin B12 and Hcy levels in these populations. Methods: A total of 719 individuals including the elderly, children, as well as pregnant and lactating women were recruited from our health care center. Folate, vitamin B12 and Hcy levels were measured by conventional methods. Genotype analyses of RFC1 A80G, GCPII C1561T and MTHFR C677T polymorphisms were performed by PCR-RFLP. Results: The overall prevalence of folate and vitamin B12 deficiencies were 0.3% and 4.9%, respectively. Folate deficiency was observed only in the elderly (0.4%) and pregnant women (0.3%), whereas vitamin B12 deficiency was observed mainly in pregnant women (7.9%) and the elderly (4.2%). Plasma Hcy concentrations were significantly higher in the elderly (33.6%). Pregnant women carrying the MTHFR 677TT genotype showed lower serum folate levels (p = 0.042) and higher Hcy levels (p = 0.003). RFC1 A80G and GCPII C1561T polymorphisms did not affect folate and Hcy levels in the study group. After a multivariate analysis, Hcy levels were predicted by variables such as folate, vitamin B12, gender, age and RFC1 A80G polymorphism, according to the groups studied. Conclusion:Our results suggest that folate deficiency is practically nonexistent in the post-folic acid fortification era in the subgroups evaluated. However, screening for vitamin B12 deficiency may be particularly relevant in our population, especially in the elderly.

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This study was based on the preparation, characterization, and animal in vivo experiments performed to evaluate nanoparticles of poly(ɛ-caprolactone) (PCL) and chitosan as carriers of enoxaparin. The nanoparticles were characterized and presented satisfactory results in terms of size, polydispersity, and encapsulation efficiency. Anticoagulant activity of the nanoparticles was maintained for 14 hours when the administration was subcutaneous; however no activity was observed after oral administration. There was a significant reduction in thrombus size, in vivo, for both free and encapsulated enoxaparin in comparison with the control group after subcutaneous administration. Oral administration results however were indifferent. In conclusion, the double emulsion method w/o/w was efficient for enoxaparin encapsulation, producing spherical nanoparticles with high encapsulation efficiency. For in vivo studies, the encapsulated enoxaparin showed a sustained anticoagulant activity for a higher period of time compared to free enoxaparin, with an antithrombotic effect when administered subcutaneously.

Single nucleotide polymorphisms (SNP) associated with Venous Thromboembolism (VTE) risk have been identified in European and American populations. Replicate SNPs associated with VTE in a Brazilian multicenter case-control study of the Southeast region. Patients with previous VTE assisted at the Outpatient Clinics of 3 centers of the Southeast Brazilian region were compared to normal controls of the same geographic region. We evaluated 29 SNPs associated with VTE risk in other populations, and 90 SNPs for stratification analysis of the population. Due to high admixture of Brazilian population and lack of previous studies, the calculation of the sample power was performed after genotyping. Sample size, allelic frequency and Hardy-Weinberg equilibrium were estimated. The association and odds ratio analyses were estimated by logistic regression and the results were adjusted for multiple tests using Bonferroni correction. The evaluation of the genetic structure similarity in the cases and controls was performed by AMOVA. 436 cases and 430 controls were included. It was demonstrated that this sample has a statistical power to detect a genetic association of 79.4%. AMOVA showed that the genetic variability between groups was 0.0% and 100% within each group. None of the SNPs showed association with VTE in our population. A Brazilian multicenter case-control study with adequate sample power, high genetic variability though no stratification between groups, showed no replication of SNPs associated with VTE. The high admixture of Brazilian population may be responsible for these results, emphasizing the influence of the population genetic structure in association studies.

3181 Introduction: Elevated levels of inflammatory markers and clotting factors have been related to the pathogenesis of DVT. Particularly, the balance between VWF and ADAMTS 13 activity has been previously described in patients with thrombosis. VWF levels are also described to be elevated during inflammatory processes and therefore could play a role linking the activation of inflammatory and coagulation systems in patients with DVT. Objective: To evaluate the activity of ADAMTS13 and VWF in patients with DVT and its association with inflammatory markers. Patients and Methods: Fifty-five patients with DVT, 6 months to five years after the acute episode, attended at the Hematology Center of UNIFESP were included in this study and 121 normal subjects were selected as controls. The activity of ADAMTS 13 was performed by binding of residual VWF to collagen; VWF antigen, IL-6, IL-8, F1+2 and MCP1 was determined by ELISA and D-dimer and CRP was performed by turbidimetry. Continuous variables were analyzed by Mann- Whitney test, categorical variables by the chi-square test and Spearman rank test was used for correlation analysis. Results: Thirty-tree patients had DVT caused by transient risk factor, especially the use of oral contraceptives, and 22 patients had spontaneous DVT. No patient had renal, hepatic or malignant disease. The median ADAMTS 13 activity was not statistically different between patients (median= 65.8%) and controls (median=78.5%, p= 0.3043). The plasma levels of VWF antigen, IL-6 and CRP were higher in patients than in controls (p= 0.008, p= 0.0003 and p= 0.008, respectively). The levels of IL-8 and MCP1 did not differ betwee n patients and controls (p= 0.65 and p= 0.07, respectively). The levels of VWF correlated significantly with CRP (r= 0.28, p= 0.005) and F1+2 (r= 0.3, p= 0,02) in patients. There was an inverse correlation between ADAMTS13 activity and F1+2 concentrations (r= -0,33, p= 0.01). Conclusion: This study suggests that, even after the acute episode of DVT, a chronic inflammatory state would contribute to increasing levels of VWF in patients' plasma and hypercoagulability. The downregulation of ADAMTS13 activity may also contribute to the activation of the coagulation. However the role of ADAMTS13 in the interaction between inflammatory and coagulation systems in patients with thrombosis is yet to be determined. These factors together may contribute to recurrent DVT, which affects over 25% of patients within 10 years from the first episode. Disclosures: No relevant conflicts of interest to declare.

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