We also performed the ChIP assays for HeLa cells

with Acute VTE therefore regard the use of the cut-off of 3 points or higher more useful for the identification of high risk patients, although PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19770275 this might result in a lower specificity. Implementation of the HAS-BLED score in clinical management of 345627-80-7 biological activity patients with acute VTE should be done with caution. Although a HAS-BLED score of 3 points or higher was shown to be a good predictor and of high specificity for major bleeds in our study, the sensitivity at this cut-off was only 54.6% with a positive predictive value of 8.2%. This means that 92% of patients that are identified as high risk of bleeding during VKA therapy will not develop this event. So how could the HAS-BLED score potentially be used in daily practice of patients with acute VTE We emphasize that, regardless of the predictive value of any bleeding score, withholding anticoagulants is unacceptable in these patients, including those with a high bleeding risk. However, we do advocate that physicians take appropriate bleeding preventive measures in patients at high risk of bleeding according to the HAS-BLED score, to correct the potentially reversible risk factors such as adequate control of blood pressure, frequent INR monitoring, and withholding non-steroidal anti-inflammatory drugs or platelet-inhibitors. Moreover, patient education about anticoagulant treatment, coaching and self-monitoring of INR values may also help to prevent major bleeding complications in these patients, although the effect of patient education on clinical outcomes remains unclear . Whether the HAS-BLED score can also be used to predict bleeding complications during extended VKA treatment for VTE, or during therapy with any of the novel oral anticoagulants can’t be studied in our cohort, and should be focus of future research. Our study adds clinically relevant information to the research field as we analysed the discriminative value of a simple algorithm for the endpoint of major bleeds, of which the items are readily available in daily practice. However, some aspects of our study warrant comment. First, due to its retrospective design, 388 of 537 patients had missing information on one or more items of the HAS-BLED score, most frequently on alcohol use. These elements were analyzed as normal, as indicated by previous studies. This could have resulted in an underestimation of a patient’s bleeding risk as assessed by the HAS-BLED score. Importantly, sensitivity analyses excluding either patients with missing items or including all patients but excluding the item of alcohol use on the HAS-BLED score demonstrated similar results on the discriminative value of this PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19767819 bleeding score. Second, we cannot exclude that some major bleeding events were missed, as we based our results on information available in medical records at the participating hospitals and anticoagulation clinic. However, major bleeds are serious medical events leading to evaluation in a hospital setting and thus unlikely to be missed in medical records. Moreover, our reported major bleeding incidence rate of 5/100 person years compares well to the existing literature, which makes it unlikely that events were missed. Third, the number of major bleeding events in our cohort was limited. It would therefore be valuable if the results of our study would be confirmed by larger cohorts of acute VTE patients. Fourth, we excluded 163 of 700 patients as they had not been treated for their acute VTE event by one of the three designated hospitals. However,