PTH6: PATIENTS' PERCEPTIONS OF THE OUTCOMES OF TREATMENT WITH TOPICAL NSAIDS, RUBIFACIANTS AND ORAL PAIN REMEDIES. A PROSPECTIVE STUDY OF MEDICINES AVAILABLE THROUGH COMMUNITY PHARMACIES

Obesity is a major health concern not only in the general population but also in patients with haemophilia. Little is known about the consequences of obesity for haemophilia patients. As obesity is an important risk factor for osteoarthritis, these effects may be even more pronounced in haemophilia patients who are prone to joint damage. The association between obesity and limitations in daily activities as well as the frequency of bleeds and use of factor VIII (FVIII) concentrate in obese and normal weight haemophilia patients was assessed. Fifteen obese (BMI≥30kgm-2) and fifteen normal weight (BMI≤25kgm-2) haemophilia A patients matched for severity and age were analysed. The Hemophilia Activities List (HAL) was used to assess the impairment in daily activities. Compared with the normal weight haemophilia patients, obese haemophiliacs had a significantly lower sum score (88/100 and 98/100, respectively, P=0.02), which was mainly caused by an impaired lower limb function. All other components of the HAL also showed lower scores in the obese patients, but did not reach statistical significance. A higher frequency of bleeds requiring treatment with FVIII concentrate occurred in the obese haemophiliacs (17 bleeds in eight individuals) compared with the controls (three bleeds in three individuals) (P=0.045). Compared with non-obese haemophilia patients, obese haemophiliacs had more joint bleeds and a lower overall HAL score, which was driven by a lower limb function score. Prevention of overweight and weight reduction requires special attention from physicians treating haemophilia patients. © 2011 Blackwell Publishing Ltd

Evaluation of coagulation activation after Rhinovirus infection in patients with asthma and healthy control subjects: an observational study

Background Asthma exacerbations are frequently triggered by rhinovirus infections. Both asthma and respiratory tract infection can activate haemostasis. Therefore we hypothesized that experimental rhinovirus-16 infection and asthmatic airway inflammation act in synergy on the haemostatic balance. Methods 28 patients (14 patients with mild allergic asthma and 14 healthy non-allergic controls) were infected with low-dose rhinovirus type 16. Venous plasma and bronchoalveolar lavage fluid (BAL fluid) were obtained before and 6 days after infection to evaluate markers of coagulation activation, thrombin-antithrombin complexes, von Willebrand factor, plasmin-antiplasmin complexes, plasminogen activator inhibitor type-1, endogenous thrombin potential and tissue factor-exposing microparticles by fibrin generation test, in plasma and/or BAL fluid. Data were analysed by nonparametric tests (Wilcoxon, Mann Whitney and Spearman correlation). Results 13 patients with mild asthma (6 females, 19-29 y) and 11 healthy controls (10 females, 19-31 y) had a documented Rhinovirus-16 infection. Rhinovirus-16 challenge resulted in a shortening of the fibrin generation test in BAL fluid of asthma patients (t = -1: 706 s vs. t = 6: 498 s; p = 0.02), but not of controls (t = -1: 693 s vs. t = 6: 636 s; p = 0.65). The fold change in tissue factor-exposing microparticles in BAL fluid inversely correlated with the fold changes in eosinophil cationic protein and myeloperoxidase in BAL fluid after virus infection (r = -0.517 and -0.528 resp., both p = 0.01). Rhinovirus-16 challenge led to increased plasminogen activator inhibitor type-1 levels in plasma in patients with asthma (26.0 ng/mL vs. 11.5 ng/mL in healthy controls, p = 0.04). Rhinovirus-16 load in BAL showed a linear correlation with the fold change in endogenous thrombin potential, plasmin-antiplasmin complexes and plasminogen activator inhibitor type-1. Conclusions Experimental rhinovirus infection induces procoagulant changes in the airways of patients with asthma through increased activity of tissue factor-exposing microparticles. These microparticle-associated procoagulant changes are associated with both neutrophilic and eosinophilic inflammation. Systemic activation of haemostasis increases with Rhinoviral load

Statins, fibrates, and venous thromboembolism: a meta-analysis.

Aims The aim is to make a systematic review of the literature to assess the effect of lipid-lowering drugs on venous thromboembolism (VTE) occurrence. Methods and results MEDLINE and EMBASE databases were searched to identify studies that evaluated the effect of lipid-lowering drugs, in particular statins and fibrates, on VTE risk until April 2009. A scoring system was used to divide studies into two quality categories. Odds ratios (ORs) and 95% confidence intervals (CIs) were then calculated and pooled using a fixed and a random-effects model. Statistical heterogeneity was evaluated through the use of I2 statistics. Three randomized controlled trials (RCTs), three cohort, and eight case\u2013control studies were included in our systematic review, for a total of 863 805 patients. Statins use significantly reduced VTE risk [OR, 0.81; 95% CI, 0.66\u20130.99, random-effect model)]. There was a very high heterogeneity among the studies (I2 > 80%). The use of fibrates was associated with a significant increase in the risk of VTE (OR, 1.58; 95% CI, 1.23\u20132.02), without heterogeneity (I2 = 0%). Data on other lipid-lowering drugs were lacking. Conclusion This meta-analysis of available literature suggests that statins may lower the risk of VTE, whereas fibrates may increase this risk. Due to several methodological limitations, this conclusion should be considered with caution, and additional, specifically designed RCTs are warranted

Idarucizumab for Dabigatran Reversal - Full Cohort Analysis.

BACKGROUND: Idarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran. METHODS: We performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the diluted thrombin time or ecarin clotting time. Secondary end points included the restoration of hemostasis and safety measures. RESULTS: A total of 503 patients were enrolled: 301 in group A, and 202 in group B. The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100 to 100), on the basis of either the diluted thrombin time or the ecarin clotting time. In group A, 137 patients (45.5%) presented with gastrointestinal bleeding and 98 (32.6%) presented with intracranial hemorrhage; among the patients who could be assessed, the median time to the cessation of bleeding was 2.5 hours. In group B, the median time to the initiation of the intended procedure was 1.6 hours; periprocedural hemostasis was assessed as normal in 93.4% of the patients, mildly abnormal in 5.1%, and moderately abnormal in 1.5%. At 90 days, thrombotic events had occurred in 6.3% of the patients in group A and in 7.4% in group B, and the mortality rate was 18.8% and 18.9%, respectively. There were no serious adverse safety signals. CONCLUSIONS: In emergency situations, idarucizumab rapidly, durably, and safely reversed the anticoagulant effect of dabigatran. (Funded by Boehringer Ingelheim; RE-VERSE AD ClinicalTrials.gov number, NCT02104947 .)