Proprotein convertase subtilisin/kexin type 9 (PCSK9) levels in primary antiphospholipid syndrome. The multicenter ATHERO-APS study.

BACKGROUND: The proprotein convertase subtilisin/kexin type 9 (PCSK9) is emerging as a novel cardiovascular risk factor. Levels of PCSK9 in thrombotic primary antiphospholipid syndrome (PAPS) have never been investigated. METHODS: Cross sectional comparison of baseline characteristics of 91 PAPS patients enrolled in the multicenter prospective ATHERO-APS cohort study. PCSK9 levels were categorized into tertiles and the association with arterial and recurrent thrombosis were assessed by univariable and multivariable logistic regression analysis. RESULTS: Median age was 51 years and 71.4% (n = 65) were women. Overall, 33% (n = 30) experienced an arterial event while 31% (n = 28) had recurrent thrombotic events. Median PCSK9 levels were 1243 (1100-1650) pg/ml. Patients in the third PCSK9 tertile (>1458 pg/ml) showed a higher prevalence of dyslipidemia, lupus anticoagulant positivity and a history of previous arterial and recurrent thrombosis than patients in the first and second tertile. PCSK9 levels were higher in arterial than venous thrombosis (1502 vs. 1180 pg/ml, p = 0.002), and in patients with recurrent vs isolated thrombosis (1680 vs. 1150 pg/m, p < 0.001). High plasma PCSK9 levels were associated with a 4-fold increase risk for arterial events and with a 10-fold increase risk for recurrent thrombosis after adjustment for confounding factors. CONCLUSION: These preliminary data suggest that PCSK9 levels are increased in PAPS patients with arterial and recurrent thrombosis. Its role as a possible therapeutic target in PAPS needs further studies.

Validity of Coagulation Activation Markers in Antiphospholipid Syndrome: A Systematic Review and Meta-analysis with a Short Data Report.

Prothrombin fragment F1 + 2 (F1 + 2) and thrombin-antithrombin (TAT) have been assessed in antiphospholipid syndrome (APS) but without evaluating a direct relationship with antiphospholipid (aPL) antibody titers. This article aims to investigate a direct relationship between aPL and F1 + 2 and perform a systematic review and meta-analysis of F1 + 2 and TAT in APS. Systematic search was performed using EMBASE and PubMed databases from January 1982 to December 2018 and random effects meta-analyses for continuous outcomes. This is a cross-sectional case-control study; immunoglobulin G/immunoglobulin M (IgG/IgM) anticardiolipin (aCL) anti-ß2-glycoprotein-I, antiprothrombin (aPT) antibodies, F1 + 2, and lupus anticoagulants (LA) were measured in 25 thrombotic primary APS (PAPS), 9 nonthrombotic carriers of aPL, and 18 controls. The significant effect size (ES) for F1 + 2 between aPL +ve and aPL -ve systemic lupus erythematosus (SLE) and between aPL +ve SLE and control displayed high heterogeneity. The significant ES for F1 + 2 between aPL -ve SLE and controls displayed no heterogeneity. The ES for TAT between aPL +ve and aPL -ve SLE patients and between aPL -ve SLE and controls was low, without heterogeneity. Mean F1 + 2 was greater in PAPS (p < 0.0001), inversely correlated with IgG aCL, IgM aPT, and LA (p = 0.001, 0.03, and 0.01, respectively), though only IgG aCL negatively predicted F1 + 2 (p = 0.01). IgG aCL inversely predicts F1 + 2. IgG aCL positivity introduces heterogeneity in the F1 + 2 ES, whereas the lack of heterogeneity in the ES for TAT may indicate poor TAT formation in aPL +ve group. Thus, F1 + 2 measurements may be unfounded as already demonstrated for TAT in the 1990s.

Practical Suggestions for an Optimal Management of Vitamin K Antagonists: Italian Federation of Centers for the Diagnosis of Thrombotic Disorders and the Surveillance of the Antithrombotic Therapies (FCSA) Position Paper.

In the era of direct oral anticoagulants, vitamin K antagonists retain a clinically relevant role in thrombotic disorders. In Italy, approximately 20% of the patients on anticoagulant therapies receives a VKA, in most cases warfarin. The optimal management of this drug is challenging and cannot disregard its intricate and unpredictable pharmacokinetic properties and patient's thrombotic and bleeding risk. Several clinical issues encountered during warfarin treatment are still unanswered and are tentatively addressed by physicians. In this regard, the Italian Federation of Centers for the diagnosis of thrombotic disorders and the Surveillance of the Antithrombotic therapies (FCSA) provides some experience-based good clinical practice's suggestions on the following topics: (1) how to start the anticoagulant treatment with warfarin and warfarin induction regimen; (2) how to manage a subtherapeutic INR value; (3) how to manage a supratherapeutic INR value in asymptomatic patients; and (4) how to manage the association of warfarin with interfering drugs.

More early bleeds associated with high baseline direct oral anticoagulant levels in atrial fibrillation: the MAS study.

ABSTRACT: Treatment with direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) is effective and safe. However, bleeding complications still occur. Whether DOAC level measurement may further improve treatment efficacy and safety is still an open issue. In the "Measure and See" study, venous blood was collected 15-30 days after DOAC initiation in patients with AF who were then followed up for 1 year to record the occurrence of major and clinically relevant nonmajor bleeding. DOAC plasma levels were measured in 1 laboratory, and results were kept blind to patients and treating doctors. Trough DOAC levels were assessed in 1657 patients (957 [57.7%] and 700 patients treated with standard and low-dose, respectively). Fifty bleeding events were recorded during 1606 years of follow-up (3.11% pt/yrs). Fifteen bleeding events (4.97% pt/yrs) occurred in patients with C-trough standardized values in the highest activity class (>0.50), whereas 35 events (2.69% pt/yrs) occurred in those with values in the 2 lower classes (≤0.50, P = .0401). Increasing DOAC levels and low-dose DOAC use were associated with increased bleeding risk in the first 3 months of treatment. Overall, 19% of patients receiving low doses had standardized values in the highest class. More bleeding occurred in patients on low (4.3% pt/yrs) vs standard (2.2% pt/yrs; P = .0160) dose DOAC. Early measurement of DOAC levels in patients with AF identified many individuals with high levels despite the low doses use and had more bleeding risk during the first 3 months of treatment. This trial was registered at www.ClinicalTrials.gov as #NCT03803579.

Thrombotic events associated with low baseline direct oral anticoagulant levels in atrial fibrillation: the MAS study.

ABSTRACT: Although effective and safe, treatment with direct oral anticoagulants (DOAC) in atrial fibrillation (AF) is still associated with thrombotic complications. Whether the measurement of DOAC levels may improve treatment efficacy is an open issue. We carried out the observational, prospective, multicenter Measure and See (MAS) study. Blood was collected 15 to 30 days after starting DOAC treatment in patients with AF who were followed-up for 1 year. Plasma samples were centralized for DOAC level measurement. Patients' DOAC levels were converted into drug/dosage standardized values to allow a pooled analysis in a time-dependent, competitive-risk model. The measured values were transformed into standardized values (representing the distance of each value from the overall mean) by subtracting the DOAC-specific mean value from the original values and dividing by the standard deviation. Trough and peak DOAC levels were assessed in 1657 and 1303 patients, respectively. In total, 21 thrombotic complications were recorded during 1606 years of follow-up (incidence of 1.31% of patients per year). Of 21 thrombotic events, 17 occurred in patients whose standardized activity levels were below the mean of each DOAC (0); the incidence was the highest (4.82% of patients per year) in patients whose standardized values were in the lowest class (-1.00 or less). Early measurement of DOAC levels in patients with AF allowed us to identify most of the patients who, having low baseline DOAC levels, subsequently developed thrombotic complications. Further studies are warranted to assess whether thrombotic complications may be reduced by measuring baseline DOAC levels and modifying treatment when indicated. This trial was registered at www.ClinicalTrials.gov as #NCT03803579.

Low-grade endotoxemia and risk of recurrent thrombosis in primary antiphospholipid syndrome. The multicenter ATHERO-APS study.

INTRODUCTION: Low-grade endotoxemia is associated with systemic inflammation, enhanced oxidative stress and cardiovascular events in different clinical settings, but its possible role as "second hit" in patients with primary antiphospholipid syndrome (PAPS) has never been investigated. PURPOSE: To evaluate the relationship between plasma lipopolysaccharide (LPS) levels, oxidative stress markers and risk of thrombosis in the prospective multicenter ATHERO-APS study. METHODS: Baseline LPS, soluble NADPH-oxidase 2-derived peptide (sNOX-dp), H2O2 production, hydrogen peroxide breakdown activity (HBA), and nitric oxide (NO) bioavailability were compared in 97 PAPS, 16 non-thrombotic aPL carriers and 21 controls (CTRL) matched for age and sex. Correlations among laboratory variables were explored by Rho Spearman's correlation (rS). Cox-regression analysis was performed to assess the association between LPS and risk for a composite outcome of cardiovascular death, venous and arterial thromboembolism. RESULTS: In the whole cohort (median age 51 years (IQR 43-60), 72 % female), PAPS demonstrated higher levels of LPS, sNOX-dp and H2O2 and lower levels of NO and HBA compared to non-thrombotic aPL carriers and CTRL. LPS levels were inversely correlated with HBA (rS: -0.295, p = 0.001) and NO (rS: -0.322, p < 0.001) and directly correlated with sNOX-dp (rS:0.469, p < 0.001) and H202 (rS:0.282, p < 0.001). PAPS showed higher levels of LPS, sNOX-dp and H2O2 and lower levels of NO and HBA compared to aPL carriers and CTRL. After a 4.7 years follow-up of, 11 composite outcomes were reported in PAPS (2.5 per 100 patient-years) while none was observed in aPL carriers. On Cox-regression analysis, patients with LPS above the median (>23.1 pg/ml) had a 5-fold increased risk of composite outcome compared to those with LPS below the median, after adjustment for sex, age, diabetes, and global antiphospholipid syndrome score. CONCLUSION: Low-grade endotoxemia is associated with an increased oxidative stress and a higher risk of thrombosis in PAPS. Its prognostic value in carriers needs to be investigated in larger cohorts.

Cardiac and vascular features of arterial and venous primary antiphospholipid syndrome. The multicenter ATHERO-APS study.

BACKGROUND: Patients with primary antiphospholipid syndrome (PAPS) may suffer from venous and/or arterial thrombosis, but studies addressing eventual clinical and laboratory features that may discriminate between arterial thromboembolism (ATE) from venous thromboembolism (VTE) have been poorly addressed. METHODS: Cross sectional comparison of baseline characteristics of 100 patients enrolled in the multi center ATHERO-APS cohort study; patients with previous ATE and VTE were compared with regards to clinical and biochemical variables as well as to echocardiographic features and ankle-brachial index (ABI) measured at enrolment. RESULTS: Mean age of patients was 51 years, 72 were women. 60 patients suffered VTE and 40 ATE. Compared to VTE, ATE patients displayed a higher prevalence of hypertension (43.3% vs. 65%, p = 0.034) and diabetes (3.3% vs. 17.5%, p = 0.015). Mean concentration of inflammation and complement activation markers were similar between the two groups as well as autoantibodies titres; mean D-dimer concentration was greater in VTE patients (184 ng/ml vs. 347 ng/ml; p = 0.024) whereas mean platelet count was greater in ATE patients (263 × 109/L vs 216 × 109/L, p = 0.044). By multivariable logistic regression analysis, adjusted for age, sex, hypertension and diabetes, ABI ≤ 0.9 (OR: 3.4; p = 0.041) and left atrial enlargement (OR: 3.5; p = 0.035) were associated with a history of ATE. ATE patients had a higher prevalence of ABI <0.9 (32.5% vs 10% p = 0.005) than VTE patients. At logistic regression analysis, IgG aCL >120 GPL U/ml was associated with an ABI ≤0.9 (OR: 5; p = 0.023) after adjustment for age and sex. CONCLUSION: Clinical, laboratory and cardiovascular variables distinguish arterial from venous APS patients, amongst which the ABI and left atrial enlargement. Implications for these two distinct clinical phenotypes of APS patients need further investigation.

Management of DOAC in Patients Undergoing Planned Surgery or Invasive Procedure: Italian Federation of Centers for the Diagnosis of Thrombotic Disorders and the Surveillance of the Antithrombotic Therapies (FCSA) Position Paper.

Patients on anticoagulant treatment are constantly increasing, with an estimated prevalence in Italy of 2% of the total population. About a quarter of the anticoagulated patients require temporary cessation of direct oral anticoagulants (DOACs) or vitamin K antagonists for a planned intervention within 2 years from anticoagulation inception. Several clinical issues about DOAC interruption remain unanswered: many questions are tentatively addressed daily by thousands of physicians worldwide through an experience-based balancing of thrombotic and bleeding risks. Among possible valuable answers, the Italian Federation of Centers for the diagnosis of thrombotic disorders and the Surveillance of the Antithrombotic therapies (FCSA) proposes some experience-based suggestions and expert opinions. In particular, FCSA provides practical guidance on the following issues: (1) multiparametric assessment of thrombotic and bleeding risks based on patients' individual and surgical risk factor, (2) testing of prothrombin time, activated partial thromboplastin time, and DOAC plasma levels before surgery or invasive procedure, (3) use of heparin, (4) restarting of full-dose DOAC after high risk bleeding surgery, (5) practical nonpharmacological suggestions to manage patients perioperatively. Finally, FCSA suggests creating a multidisciplinary "anticoagulation team" with the aim to define the optimal perioperative management of anticoagulation.

Intensity of immune/clotting assays relate to multiple antiphospholipid antibody positivity in thrombotic primary antiphospholipid syndrome.

The dual positivity (DP) and triple positivity (TP) concepts bypass the poor comparability of immune/clotting assay for the laboratory classification of antiphospholipid syndrome (APS). To evaluate intensity of immune/clotting assays and DP/TP through different clinical severity groups (CSG) as follows: (1) non-thrombotic asymptomatic carriers of aPL (N-THR), thrombotic primary APS (THR), deceased (D) for recurrent and fatal thrombosis. Activated partial thromboplastin time ratio (aPTTr), dilute Russell viper venom time ratio (DRVVTr), IgG/IgM anticardiolipin (aCL) and anti ß-2-glycoprotein-I (aß2GPI). Participants: 33 N-THR, 64 THR and 11 D. The frequency of DP and TP (DRVVTr or aPTTr partnered with respective IgG aCL or aß2GPI) increased across CSG (p = 0.006 and p = 0.003); mean DRVVTr and IgG aCL/aß2GPI were always greater in TP versus non-TP within each CSG and progressively increased across the CSG. The intensity of individual lupus anticoagulants partnered with their corresponding IgG aPL related to the frequency of multiple positivity throughout CSG suggesting that of intensity of immune/clotting assays and multiple positivity are the different faces of the same diagnostic coin in our thrombotic PAPS cohort.

Antiphospholipid Antibodies and Heart Failure with Preserved Ejection Fraction. The Multicenter ATHERO-APS Study.

BACKGROUND: The prevalence of heart failure with preserved ejection fraction (HFpEF) in patients with antiphospholipid syndrome (APS) is unknown. METHODS: A prospective multicenter cohort study including 125 patients was conducted: 91 primary APS (PAPS), 18 APS-SLE, and 16 carriers. HFpEF was diagnosed according to the 2019 European Society of Cardiology criteria: patients with ≥5 points among major and minor functional and morphological criteria including NT-ProBNP > 220 pg/mL, left atrial (LA) enlargement, increased left ventricular filling pressure. RESULTS: Overall, 18 (14.4%) patients were diagnosed with HFpEF; this prevalence increased from 6.3% in carriers to 13.2% in PAPS and 27.8% in APS-SLE. Patients with HFpEF were older and with a higher prevalence of hypertension and previous arterial events. At logistic regression analysis, age, arterial hypertension, anticardiolipin antibodies IgG > 40 GPL (odds ratio (OR) 3.43, 95% confidence interval (CI) 1.09-10.77, p = 0.035), anti ß-2-glycoprotein-I IgG > 40 GPL (OR 5.28, 1.53-18.27, p = 0.009), lupus anticoagulants DRVVT > 1.25 (OR 5.20, 95% CI 1.10-24.68, p = 0.038), and triple positivity (OR 3.56, 95% CI 1.11-11.47, p = 0.033) were associated with HFpEF after adjustment for age and sex. By multivariate analysis, hypertension (OR 19.49, 95% CI 2.21-171.94, p = 0.008), age (OR 1.07, 95% CI 1.00-1.14, p = 0.044), and aß2GPI IgG > 40 GPL (OR 8.62, 95% CI 1.23-60.44, p = 0.030) were associated with HFpEF. CONCLUSION: HFpEF is detectable in a relevant proportion of APS patients. The role of aPL in the pathogenesis and prognosis of HFpEF needs further investigation.

Anticoagulation resumption after intracranial hemorrhage in patients treated with VKA and DOACs.

BACKGROUND: Intracranial hemorrhage (ICH) is associated with severe prognosis and recurrent risk. This impacts on the decision to resume anticoagulation in atrial fibrillation (AF) or venous thromboembolism (VTE) patients. Purpose of our study is to evaluate the incidence rate of recurrent ICH in patients with AF or VTE resuming anticoagulation after a first ICH episode. METHODS: We report data of two cohorts of AF or VTE after a first ICH. The Vitamin K antagonist (VKA) cohort (166 patients) derives from CHIRONE Study, the direct oral anticoagulant (DOAC) cohort (178 patients) derives from START2-Register RESULTS: The clinical characteristics of the two cohort are similar with the exception of more prevalence of history of previous stroke/TIA in DOAC patients with respect to VKA (p = 0.02) and serum creatinine levels>1.5 mg/dL in VKA patients with respect to DOAC(p = 0.0001). The index ICH was spontaneous in 66.4% and in 33.7% among DOAC and VKAs cohort respectively (p = 0.0001). During follow-up, 14 recurrent ICH were recorded; 9 (rate 2.5 × 100 patient-years) in VKA and 5 (rate 1.3 × 100 patient-years) in DOAC (Relative Risk 1.9; 95% CI 0.6-7.4; p = 0.2). The univariate logistic regression analysis showed that patients with recurrent ICH were more frequently males, hypertensive, with a history of previous Stroke/TIA and older than patients without recurrence. VKA patients showed a higher risk of recurrence with respect to DOAC patients (OR 1.9;95% CI 0.7-6.7). CONCLUSIONS: A trend toward fewer ICH recurrences was detected among DOACs patients in comparison to the previously reported rate of patients on warfarin.

Managing anticoagulation in the COVID-19 era between lockdown and reopening phases.

Patients on anticoagulant treatment are constantly increasing, with an estimated prevalence in Italy of 2% of the total population. The recent spreadout of the COVID-19 pandemic requires a re-organization of Anticoagulation Clinics to prevent person-to-person viral diffusion and continue to offer the highest possible quality of assistance to patients. In this paper, based on the Italian Federation of Anticoagulation Clinics statements, we offer some advice aimed at improving patient care during COVID-19 pandemic, with particular regard to the lockdown and reopening periods. We give practical guidance regarding the following points: (1) re-thinking the AC organization, (2) managing patients on anticoagulants when they become infected by the virus, (3) managing anticoagulation surveillance in non-infected patients during the lockdown period, and (4) organizing the activities during the reopening phases.

Oral anticoagulation cost in primary antiphospholipid syndrome: comparison between warfarin and hypothetical rivaroxaban.

: The objective of the study is to perform a cost comparison of 1 year of oral anticoagulation management with warfarin vs. hypothetical rivaroxaban (RRX) in thrombotic primary antiphospholipid syndrome. Longitudinal study on 20 primary antiphospholipid syndrome patients followed-up for 1 year after anticoagulation stabilisation with warfarin: a dedicated software calculated number of clinic visits, time in therapeutic range and warfarin consumption for each patient; for RRX, we considered a visit every 3 months (baseline done in hospital before attending anticoagulant clinic); knowing the cost of both anticoagulants, the laboratory cost and the human cost we calculated and compared the yearly expenditure. Average time in therapeutic international normalized ratio range was 69 ±â€Š11%: warfarin management required a total of 375 of visits compared with the 60 for RRX; the yearly cost of RRX was superior to that of warfarin (12 012 vs. 446.4 euros, P < 0.0001), and in spite of lower laboratory (738 vs. 1853 euros, P < 0.0001) and human costs (774.6 vs. 4841 euros), RRX thromboprophylaxis still yielded a hefty bill (13 525 vs. 7140 euros, P < 0.0001). Switching from warfarin to RRX will be 48% more expensive to our Healthcare Authority; unless ongoing clinical trials demonstrate improved long-term outcomes for RRX over warfarin, we feel that a 69% time in therapeutic range does not warrant a change to RRX at a 48% increased cost.

Bleeding and re-thrombosis in primary antiphospholipid syndrome on oral anticoagulation: an 8-year longitudinal comparison with mitral valve replacement and inherited thrombophilia.

The aim of this study was to compare bleeding and re-thrombosis in primary antiphospholipid syndrome (PAPS), mitral valve replacement (MVR) and inherited thrombophilia (IT) at different oral anticoagulation intensities. It entailed a prospective 8-year follow-up on 67 patients with PAPS, 89 with IT and 24 with MVR. Anticardiolipin (aCL) antibodies detected by Elisa and lupus anticoagulant by clotting assays. At INR 2-3 minor bleeding rate was higher in MVR (33.3) than PAPS (10.9) and IT (4.2)(p<0.0001). At INR 3-4 minor bleeding rate was higher in PAPS (142) than IT (33.3) and MVR (5.8)(p<0.0001). At either INR major bleeding rate were not significantly different across the three groups, but in PAPS major and minor bleeding rates were superior at INR 3-4 than INR 2-3 (p=0.02 and p<0.0001). Re-thrombosis rate was higher in PAPS than IT at INR 2-3 (4.0 vs 0.35) (p=0.01) and at INR 3-4 (10.5 vs. nil). The hazard ratio for re-thrombosis between PAPS and IT was 13 (95% IC 1.6-102.2, p=0.015). By regression analysis, baseline IgG aCL titre (>80 GPL) p=0.001) and male sex (p=0.03) independently predicted re-thrombosis. In conclusion, in PAPS, high intensity oral anticoagulation was not superior to conventional intensity in preventing re-thrombosis but was offset by greater bleeding rates. Male sex and elevated baseline IgG aCL predicted rethrombosis in PAPS that is 13-fold more re-thrombogenic than IT.

Autonomia e orientação esportiva no comportamento moral de atletas de rendimento / Autonomy and sportspersonship orientation in the moral behavior of thletes

Este estudo propõe um Modelo Explicativo de Moral no esporte verificando a percepção de autonomia e sua influência no comportamento pró e antissocial nos atletas, mediados pela orientação esportiva. Foram avaliados 180 atletas da Região Sul do Brasil de ambos os sexos participantes em competições nacionais ou internacionais. Os instrumentos utilizados foram: Escala de Satisfação de Necessidades Básicas no Esporte (BNSSS); Escala Multidimensional de Orientação Esportiva (MSOS); e Escala de Comportamento Pró-social e Antissocial no Esporte (PABSS). Os dados foram analisados por meio de um Modelo de Equações Estruturais. Os atletas apresentaram valores elevados de autonomia, julgamento independente, respeito às regras, convenções sociais e comportamentos pró-sociais, com baixos valores de comportamentos antissociais. O modelo de equações estruturais testado demonstra que a orientação esportiva pode ser uma variável mediadora entre a relação da autonomia e principalmente os comportamentos pró-sociais. Conclui-se que uma moral pós-convencional no esporte associada a um movimento autônomo perpassa uma orientação positiva da prática esportiva.

This study proposes an Explanatory Moral Model in sport, verifying the perception of autonomy and its influence on pro and antisocial behavior in athletes, mediated by sportspersonship orientation. 180 athletes from the southern region of Brazil of both genders participating in national and international competitions were evaluated. The instruments used were: Basic Sport Needs Satisfaction Scale (BNSSS); Multidimensional Sportspersonship Orientation Scale (MSOS); and Prosocial and Antisocial Behavior in Sport Scale (PABSS). Data were analyzed using a Structural Equation Model. The athletes showed high values of autonomy, independent judgment, respect for the rules, social conventions and prosocial behaviors, with low values of antisocial behaviors. The tested structural equation model demonstrates that sportspersonship orientation can be a mediating variable between the relationship of autonomy and especially prosocial behaviors. It is concluded that a postconventional morality in sport associated with an autonomic movement goes through a positive orientation of sports practice.

FV HR2 haplotype as additional inherited risk factor for deep vein thrombosis in individuals with a high-risk profile.

A number of strongly linked polymorphisms within the Factor V gene (FV HR2 haplotype) has been identified as a cause of resistance to activated protein C, and has suggested a modest risk factor for vein thrombosis. We investigated the frequency of the HR2 haplotype in 433 consecutive patients with confirmed deep vein thrombosis and 326 controls. The HR2 haplotype was more frequent in patients (15.2%) than in controls (10.1%). The risk of thrombosis among carriers of this haplotype was significantly increased (odds ratio: 1.6 [95% CI: 1.0-2.5]). The estimated risk associated with the HR2 haplotype was 1.8 (95% CI: 1.1-2.9) in subjects with (n = 255), and 1.4 (95% CI: 0.8-2.4) in those without (n = 178) acquired risk factors for vein thrombosis. After adjustment for sex, FV Leiden and FII A20210 mutations, the estimated risk of vein thrombosis among carriers of the HR2 haplotype was 1.8 (95% CI: 1.1-2.8). Present data indicate that the HR2 haplotype is independently associated with vein thrombosis among individuals with a high-risk profile.

O Mundo da Vida (Lebenswelt) enquanto instância de significação: tessituras e delimitações críticas / World of life as an instance of signification: tessitures and critical delimitations

O objetivo do presente artigo é discutir as particularidades epistemológicas nos interesses de Edmund Husserl, Alfred Schütz e Jürgen Habermas pelo Mundo da Vida (Lebenswelt), enquanto instância de significação da vida. Para tanto, além das obras de autores supracitados, também apresentamos e discutimos produções da filosofia, da sociologia e da psicologia que problematizam epistemologicamente o Mundo da Vida. A presente discussão tem sua relevância na medida em que apresenta as delimitações teóricas do construto do Mundo da Vida, mediante a tessitura de críticas dos referidos autores. De forma geral, este artigo se estrutura e propõe as seguintes reflexões: introduzimos a concepção de Mundo da Vida enquanto instância de significação e a importância de delimitar suas diferentes perspectivas; apresentamos a inauguração das reflexões do Mundo da Vida no pensamento de Edmund Husserl; os desdobramentos do Mundo da Vida cotidiano dentro das análises da Sociologia Compreensiva de Alfred Schütz; e, por fim, a apropriação de Jürgen Habermas para a construção de sua Teoria Crítica da Sociedade.

The purpose of this article is to discuss the epistemological particularities of Edmund Husserl, Alfred Schütz and Jürgen Habermas for the World of Life (Lebenswelt), as an instance of the signification of life. Thereunto, besides the work of the authors mentioned above, we also present and discuss productions of Philosophy, Sociology and Psychology that epistemologically problematize the World of Life. The present discussion has its relevance insofar in the means that it presents the theoretical delimitations of the construct of the World of Life, through the criticism of these authors. In general, this article is structured and proposes the following reflections: we introduce the concept of the World of Life as an instance of signification and the importance of delimitating their different perspectives; we present the inauguration of the reflections of the World of Life in the thought of Edmund Husserl; the unfoldings of the everyday World of Life within the analyzes of Alfred Schütz's Comprehensive Sociology; and, finally, the appropriation of Jürgen Habermas for the construction of his Critical Theory of Society.

Successful use of rFVIIa for major breast surgery prophylaxis in congenital factor VII deficiency.

INTRODUCTION: Factor VII deficiency is a rare cause of haemorrhagic syndrome. The Authors describe a case of a 46 years old patient with congenital factor VII deficiency that successfully underwent breast surgery after treatment with Novoseven® before the procedure. MATERIALS AND METHODS: The AA used the schedule reported below to value the levels of PT and aPTT in the patient. Blood Collection: Venous blood from patient and control was collected in glass tubes for routine serum preparation and into plastic tubes (0.129 M sodium citrate, Becton-Dickinson Vacutainer Systems) in a ratio of blood to anticoagulant of 9:1. Platelet Poor Plasma (PPP) was obtained by centrifugation at 4.000 x g for 15 minutes at room temperature. The plasma was recentrifuged for another 10 min at 12000 g to fully eliminate platelet concentration. A normal control plasma pool was prepared by mixing equal volumes of platelet-free plasma obtained from at least 50 normal volunteers. Prothrombin time (PT) was measured with Recombiplastin (IL, Milano Italy). Activated partial thromboplastin times (APTT) was measured with APTT-SP (IL, Milano Italy). They were performed on the coagulation analyzer ACL 1000 (IL, Milano Italy). RESULTS: The results were interpreted from the ratio of the patient times to the normal control times (Table I). CONCLUSION: The infusion of Novoseven solved the clotting problems enabling the surgical procedure, without risks for the patient. KEY WORDS: Breast cancer, Factor VII deficiency, Major surgery, Recombinant fVIIa.

Successful use of rFVIIa for major breast surgery prophylaxis in congenital factor VII deficiency: a case report.

INTRODUCTION: Factor VII deficiency is a rare cause of haemorrhagic syndrome. The Authors describe a case of a 46 years old patient with congenital factor VII deficiency that successfully underwent breast surgery after treatment with Novoseven® before the procedure. MATERIALS AND METHODS: The AA used the schedule reported below to value the levels of PT and aPTT in the patient. Blood Collection: Venous blood from patient and control was collected in glass tubes for routine serum preparation and into plastic tubes (0.129 M sodium citrate, Becton-Dickinson Vacutainer Systems) in a ratio of blood to anticoagulant of 9:1. Platelet Poor Plasma (PPP) was obtained by centrifugation at 4.000 x g for 15 minutes at room temperature. The plasma was recentrifuged for another 10 min at 12000 g to fully eliminate platelet concentration. A normal control plasma pool was prepared by mixing equal volumes of platelet-free plasma obtained from at least 50 normal volunteers. Prothrombin time (PT) was measured with Recombiplastin (IL, Milano Italy). Activated partial thromboplastin times (APTT) was measured with APTT-SP (IL, Milano Italy). They were performed on the coagulation analyzer ACL 1000 (IL, Milano Italy). RESULTS: The results were interpreted from the ratio of the patient times to the normal control times (Table I). CONCLUSION: The infusion of Novoseven solved the clotting problems enabling the surgical procedure, without risks for the patient.