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Buenos Aires, Argentina

Pascale S.,Spirito Santo Hospital | Dragani A.,Spirito Santo Hospital | Habib A.,American University of Beirut | Rolandi G.,Hemostasis and Thrombosis Laboratory
Blood | Year: 2012

Essential thrombocythemia (ET) is characterized by enhanced platelet generation and thrombotic complications. Oncedaily low-dose aspirin incompletely inhibits platelet thromboxane A 2 (TXA 2) in the majority of ET patients. In the present study, we investigated the determinants of aspirin-insensitive platelet TXA 2 biosynthesis and whether it could be further suppressed by changing the aspirin dose, formulation, or dosing interval. In 41 aspirin-treated ET patients, the immature platelet count predicted serum TXB 2 independently of platelet count, age, JAK-2 V617F mutation, or cytoreduction (β = 3.53, P = .001). Twenty-one aspirin-treated patients with serum TXB 2 ≥ 4 ng/mL at 24 hours after dosing were randomized to the following 7-day regimens in a crossover design: enteric-coated aspirin 100 mg twice daily, enteric-coated aspirin 200 mg once daily, or plain aspirin 100 mg once daily. A twice-daily regimen caused a further 88% median (IQR, 78%-92%, P < .001) TXB2 reduction and normalized the functional platelet response to aspirin, as assessed by urinary 11-dehydro-TXB 2 excretion and the VerifyNow Aspirin assay. Doubling the aspirin dose reduced serum TXB 2 only partially by 39% median (IQR, 29%-54%, P < .05). We conclude that the abnormal megakaryopoiesis characterizing ET accounts for a shorterlasting antiplatelet effect of low-dose aspirin through faster renewal of platelet cyclooxygenase-1, and impaired platelet inhibition can be rescued by modulating the aspirin dosing interval rather than the dose. © 2012 by The American Society of Hematology.

Munoz S.A.,Hospital General de Agudos | Aranda F.,Hemostasis and Thrombosis Laboratory | Allievi A.,Hospital General de Agudos | Orden A.O.,Clinica San Camilo | And 11 more authors.
Clinical and Experimental Medicine | Year: 2014

We investigated the relationship between the 4G/5G plasminogen activator inhibitor (PAI-1) and -308 A/G tumor necrosis factor-α (TNF-α) polymorphisms and the clinical and biochemical features of systemic lupus erythematosus (SLE) in an Argentinean patient cohort. A total of 402 patients were studied, including 179 SLE patients and 223 healthy individuals. PCR-RLFP was used to determine the genotypes of the 4G/5G PAI-1 and -308 A/G TNF-α polymorphisms. SLE patients with lupus nephritis (LN) (n = 86) were compared with patients without LN (n = 93). Additionally, LN patients were divided into proliferative LN and non-proliferative LN groups according to the results of the renal biopsies. No significant differences were noted in the genotype distributions or allele frequencies of these TNF-α and PAI-1 polymorphisms between SLE patients and controls. There were higher numbers of criteria for SLE, more lupus flares and higher damage scores in LN patients, but there were similar frequencies of anti-phospholipid antibody (APA) positivity and anti-phospholipid syndrome. No significant difference was noted for any studied variable between the proliferative LN and non-proliferative LN groups except for the presence of APA. We found no significant differences in the TNF-α and PAI-1 genotype distributions or allele frequencies between groups. We found that the -308 A/G TNF-α and 4G/5G PAI-1 polymorphisms are not associated with susceptibility to SLE in an Argentinean population. We also did not find any association between the presence of any specific allele or genotype and the development of LN in SLE patients. Finally, no association was noted between either of the two polymorphisms and the severity of renal disease. © 2012 Springer-Verlag Italia.

Wingeyer S.D.P.,Hemostasis and Thrombosis Laboratory | Graffigna M.N.,Durand Hospital | Belli S.H.,Durand Hospital | Benetucci J.,Hospital of Infectious Diseases F. J. Muniz | De Larranaga G.F.,Hemostasis and Thrombosis Laboratory
Genetic Testing and Molecular Biomarkers | Year: 2012

Aim: Plasminogen activator inhibitor-1 (PAI-1) and tumor necrosis factor-α (TNF-α) are increased in the circulation of obese persons. Because a direct link between PAI-1 and TNF-α in obesity has been observed, they are candidate genes for the development of obesity. We sought to evaluate the relation between the genotypic and allelic frequencies of the-675 4G/5G PAI-1 and-308 G/A TNF-α polymorphisms and their association with the risk for obesity in an Argentinean population. Methods: A group of 110 consecutive obese persons and a group of 111 lean controls were recruited. Polymerase chain reaction was used to determine the frequency of PAI-1 and TNF-α polymorphisms; serum fasting glucose, insulin, and lipid levels were measured by standard methods. Insulin sensitivity was evaluated by using homeostasis model assessment. Results: The-308 TNF-α and-675 4G/5G PAI-1 genotype distribution did not significantly differ between the groups (p=0.544 and p=0.327, respectively). Homeostasis model assessment was the only positive independent determinant of body mass index (R2=0.493; p<0.001). Conclusion: The-675 4G/5G PAI-1 and the-308 TNF-α polymorphism variants tested in this study, individually or combined, were not associated with obesity in an Argentinean population. © 2012 Mary Ann Liebert, Inc.

Udry S.,Autoimmune | Aranda F.M.,Hemostasis and Thrombosis Laboratory | Latino J.O.,Autoimmune | De Larranaga G.F.,Hemostasis and Thrombosis Laboratory
Journal of Thrombosis and Haemostasis | Year: 2014

Summary: Background: In up to 50% of couples affected by recurrent pregnancy loss, no identifiable cause is established. Fetal and maternal factors may be equally important in the establishment and maintenance of the placental/maternal arteriovenous anastomoses. Therefore, the inheritance of thrombophilia-related genes may be an important factor in the pathophysiology of recurrent pregnancy loss. Most of the research on recurrent pregnancy loss and thrombophilia has focused on maternal factors, but little is known about the paternal contribution. Objectives: On that basis, we studied the association between inherited paternal thrombophilias and recurrent pregnancy loss in a narrowly selective group of 42 Argentine males from couples that presented without any known risk factors for recurrent pregnancy loss. Patients and methods: The genotypic distributions of factor (F) V Leiden and prothrombin G20210A among cases were compared with those from a reference group composed of 200 Argentine men. Results: We found a significant difference in the distribution of FV Leiden between both groups (16.7% vs. 3.0%), but no difference was found in the distribution of prothrombin G20210A (2.4% vs. 2.0%). Those couples with paternal FV Leiden carriage would be six times more likely to experience recurrent pregnancy loss despite no other apparent cause (OR = 6.47; 95% CI, 2.06-20.39). Conclusion: We found evidence of an association between the paternal carriage of FV Leiden and the predisposition to recurrent pregnancy loss, thereby supporting the hypothesis that genetic contributions from both parents are essential factors in the development of this obstetric disorder. © 2014 International Society on Thrombosis and Haemostasis.

Wingeyer S.P.,Hemostasis and Thrombosis Laboratory | Cunto E.,Hospital of Infectious Diseases F. J. Muniz | Nogueras C.,Hospital of Infectious Diseases F. J. Muniz | Juan J.S.,Hospital of Infectious Diseases F. J. Muniz | And 2 more authors.
Journal of Infection in Developing Countries | Year: 2012

Introduction: A patient's response to sepsis is influenced by their genetic background. Our objective was to use plasma markers, such as protein C (PC), D-dimer, Plasminogen Activator Inhibitor-1 (PAI-1) levels, and the PAI-1 rs1799889 4G/5G and Tumor Necrosis Factor-α rs1800629 G/A polymorphisms to improve classical intensive care unit (ICU) scores. Methodology: We studied 380 subjects, 166 with sepsis. We performed coagulation tests: plasma PAI-1 and PC levels were evaluated by chromogenic methods; and D-dimer was evaluated by immunoturbidimetric assay. Polymorphisms were performed using for polymerase chain reactions followed by digest with specific restriction enzyme. We acquired the APACHE and SOFA scores (time zero), sex, age, body mass index, associated co-morbidities, length of ICU stay (days), the severity of sepsis (sepsis, severe sepsis or septic shock), the HIV status and the ICU outcome (survival or death). Results: We found significant differences between patients who died (n=80) and those who survived (n=86) in terms of the ICU length of stay (6 vs. 10 days), septic shock (64 versus 24%), age (51 versus 38 years old), HIV+ condition (34 versus 16%), SOFA (7 versus 4), APACHE (19 versus 13), D-dimer (4.32 versus 2.88 ng/ml), PC (46.0 versus 63.5%) and PAI-1 (33.0 versus 16.5 UA/l). When we used a regression analysis with dichotomized variables, only the SOFA4, PAI-116, HIV status and the PAI-1 4G allele proved to be predictors of death at time zero. Conclusions: In the future, ICU scores may be further improved by adding certain genomic or plasma data. © 2012 Peres et al.

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