A score that can accurately determine the risk of major bleeding during anticoagulant therapy may help to make decisions on anticoagulant use. RIETE is an ongoing registry of consecutive patients with acute venous thromboembolism (VTE). We composed a score to predict the risk for major bleeding within three months of anticoagulant therapy. Of 19,274 patients enrolled, 13,057 (67%) were randomly assigned to the derivation sample, 6,572 to the validation sample. In the derivation sample 314 (2.4%) patients bled (fatal bleeding, 105). On multivariate analysis, age >75 years, recent bleeding, cancer, creatinine levels >1.2 mg/dl, anemia, or pulmonary embolism at baseline were independently associated with an increased risk for major bleeding. A score was composed assigning 2 points to recent bleeding, 1.5 to abnormal creatinine levels or anemia, 1 point to the remaining variables. In the derivation sample 2,654 (20%) patients scored 0 points (low risk); 9,645 (74%) 1-4 points (intermediate); 758 (5.8%) >4 points (high risk). The incidences of major bleeding were: 0.3% (95% confidence interval [CI]: 0.1-0.6), 2.6% (95% CI: 2.3-2.9), and 7.3% (95% CI: 5.6-9.3), respectively. The likelihood ratio test was: 0.14 (95% CI: 0.07-0.27) for patients at low risk;2.96 (95% CI: 2.18-4.02) for those at high risk. In the validation sample the incidence of major bleeding was: 0.1%, 2.8%, and 6.2%, respectively. In conclusion, a risk score based on six variables documented at entry can identify VTE patients at low, intermediate, or high risk for major bleeding during the first three months of therapy.

BACKGROUND Genetic and environmental factors interact in determining the risk of venous thromboembolism (VTE). The risk associated with the polymorphic variants G1691A of factor V (Factor V Leiden,FVL), G20210A of prothrombin (PT20210A) and C677T of methylentetrahydrofolate reductase (C677T MTHFR) genes has been investigated in many studies. METHODS We performed a pooled analysis of case-control and cohort studies investigating in adults the association between each variant and VTE, published on Pubmed, Embase or Google through January 2010. Authors of eligible papers, were invited to provide all available individual data for the pooling. The Odds Ratio (OR) for first VTE associated with each variant, individually and combined with the others, were calculated with a random effect model, in heterozygotes and homozygotes (dominant model for FVL and PT20210A; recessive for C677T MTHFR). RESULTS We analysed 31 databases, including 11,239 cases and 21,521 controls. No significant association with VTE was found for homozygous C677T MTHFR (OR: 1.38; 95% confidence intervals [CI]: 0.98–1.93), whereas the risk was increased in carriers of either heterozygous FVL or PT20210 (OR=4.22; 95% CI: 3.35–5.32; and OR=2.79;95% CI: 2.25–3.46, respectively), in double hterozygotes (OR=3.42; 95%CI 1.64-7.13), and in homozygous FVL or PT20210A (OR=11.45; 95%CI: 6.79-19.29; and OR: 2.79; 95%CI: 2.25 – 3.46, respectively). The stratified analyses showed a stronger effect of FVL on individuals ≤45 years (p-value for interaction = 0.036) and of PT20210A in women using oral contraceptives (p-value for interaction = 0.045). CONCLUSIONS In this large pooled analysis, inclusive of large studies like MEGA, no effect was found for C677T MTHFR on VTE; FVL and PT20210A were confirmed to be moderate risk factors. Notably, double carriers of the two genetic variants produced an impact on VTE risk significantly increased but weaker than previously thought.

Summary.  Background: Fatal bleeding is a serious consequence of anticoagulant therapy, but factors associated with fatal bleeding during the first 3 months of treatment of venous thromboembolism (VTE) are uncertain. Methods: Using data from RIETE, an ongoing registry of consecutive patients with acute VTE, we assessed risk factors for fatal bleeding among all patients. We then used this information to derive a clinical model that would stratify a patient’s risk of fatal bleeding during the first 3 months of treatment. Results: Of 24 395 patients, 546 (2.24%) had a major bleed and 135 (0.55%) had a fatal bleed. The gastrointestinal tract was the most common site (40% of fatal bleeds), followed by intracranial bleeding (25%). Fatal bleeding was independently associated with the following factors at the time of VTE diagnosis: age >75 years (OR, 2.16), metastatic cancer (OR, 3.80), immobility ≥ 4 days (OR, 1.99), a major bleed within the past 30 days (OR, 2.64), an abnormal prothrombin time (OR, 2.09), a platelet count < 100 × 109 L−1 (OR, 2.23), creatinine clearance < 30 mL min−1 (OR, 2.27), anemia (OR, 1.54), and distal deep vein thrombosis (OR, 0.39). INR at the time of bleeding is not known. A clinical prediction rule for risk of fatal bleeding that included nine baseline factors was derived. Fatal bleeding occurred in 0.16% (95% CI, 0.11–0.23) of the low‐risk, 1.06% (95% CI, 0.85–1.30) of the moderate‐risk, and 4.24% (95% CI, 2.76–6.27) of the high‐risk category. Conclusions: Patient characteristics and laboratory variables can identify patients at high risk for fatal bleeding during treatment of VTE.

The results of seven serologic tests for diagnosis of human brucellosis were evaluated. The titrated Rose Bengal test, microagglutination test, microtiter-adapted Coombs test, and immunocapture-agglutination test (Brucellacapt) were positive for all sera from patients with acute brucellosis. The immunoglobulin G (IgG), IgM, and IgA commercial enzyme immunoassays (ELISAs) failed to show specific antibodies in 3 patients, 10 patients, and 1 patient, respectively. The sensitivity of ELISA is not higher than that of conventional tests.Brucellosis is an endemic zoonotic disease in many parts of the world, notably in Mediterranean countries and the Middle East. The diagnosis of brucellosis is made by the isolation of Brucella species (i.e., in blood cultures), but this method is successful in only 40 to 70% of cases (18). Therefore, laboratory diagnosis of brucellosis very often relies on detecting specific serum antibodies (5, 19). Several serological tests have been used for the diagnosis of human brucellosis. The serum agglutination test (SAT) for brucellosis, developed by Wright et al. in 1897 (17), is still the reference to which other tests are compared. Other notable tests that have been developed since then are the Rose Bengal test, complement fixation test, indirect Coombs test, enzyme immunoassay (ELISA) (6, 15), and, more recently, an immunocapture-agglutination test (Brucellacapt) (10). However, the interpretation of these tests is often difficult in areas of endemicity in which a large part of the population has contact with animals or products of animal origin and could develop antibodies against Brucella. In this study, the results obtained with seven different tests for detection of Brucella-specific antibodies in an area of endemicity were analyzed. A 12-month clinical and serologic follow-up was performed after the treatment was started. As a reference, the antibody levels in the healthy population of that area were also tested.One hundred twenty serum samples from 25 patients with acute brucellosis and 90 from healthy individuals (blood donors) were included in this study. The diagnosis of brucellosis was based on clinical findings and on either positive blood cultures for Brucella or the presence of serum antibodies (SAT titer Ն 160). At least three blood cultures were drawn from each patient at diagnosis. Follow-up cultures were drawn at the end of the treatment and 3, 6, and 12 months later. For four patients the 12-month cultures were not performed. Brucella was identified according to MunichЈs taxonomy criteria (8). Serum samples were collected on admission and 1, 3, 6, and 12 months later. For four patients the 12-month control sample was not assayed. For the group of blood donors only one serum sample was analyzed. The titrated Rose Bengal test, microagglutination test (MAT), microtiter-adapted Coombs test, Brucellacapt, and ELISAs for immunoglobulin M (IgM), IgG, and IgA antibodies were performed on each serum sample. The microtiter-adapted Coombs test was not performed for the group of hea...