Key Points• Factor XI deficiency is associated with reduced risk of cardiovascular events.• Factor XI deficiency is associated with reduced risk of VTE.Factor XI deficiency is one of the rare inherited coagulation factor deficiencies. However, its incidence is high within the Ashkenazi Jewish community. Because factor XI displays both procoagulant and antifibrinolytic activities, it has been postulated that an underlying cardiovascular benefit may exist with factor XI deficiency. This historical cohort study was performed using the electronic database of Clalit Health Services, the largest health care provider in Israel. All adults tested for factor XI activity between 2002 and 2014 were included in the study. Factor XI activity was classified into 3 categories: normal (activity >50%), mild deficiency (activity 5 30%-50%), and moderate-severe deficiency (activity £30%). The cohort was followed until 31 December 2015 for incidence of cardiovascular events (composite of myocardial infarction, stroke, and transient ischemic attack) and venous thromboembolism (VTE). Of the 10 193 included patients, 8958 (88.9%) had normal factor XI activity, 690 (6.8%) had mild deficiency, and 542 (5.3%) had moderate-severe deficiency. Compared with individuals with normal activity, the adjusted hazard ratio (HR) for cardiovascular events was 0.52 (95% confidence interval [CI], 0.31-0.87) in those with mild deficiency, and 0.57 (95% CI, 0.35-0.93) in those with moderate-severe factor XI deficiency. The incidence of VTE was lower in those with factor XI deficiency (activity <50%) compared with those with normal activity; adjusted HR 5 0.26 (95% CI, 0.08-0.84). In summary, factor XI deficiency is associated with decreased incidence of cardiovascular events and VTE. (Blood. 2017;129(9):1210-1215

The purpose of this study was to assess the association between reduced apixaban dose and two outcomes: ischemic stroke/systemic embolism (SE) and major bleeding. We performed a retrospective cohort study within the database of the largest healthcare provider in Israel. We identified all patients diagnosed with atrial fibrillation, who started apixaban treatment between 2013 and 2017. Apixaban users were classified into three dosing regimen groups based on their renal function, age, and weight: standard dose (5 mg b.i.d.), adjusted reduced dose (2.5 mg b.i.d.), and underdosing (2.5 mg b.i.d.). Patients were followed through 2018 for the occurrence of stroke/SE and major bleeding. Of the 27,765 included patients, 13,141 (47%) adequately received standard apixaban dose, 4,739 patients (17%) received adjusted reduced dose, and 9,885 patients (36%) were classified as underdosed. The CHA2DS2-VASc score adjusted hazard ratio for ischemic stroke/SE was 1.1 (95% confidence interval (CI), 0.83-1.43) in the adjusted reduced dose group, and 1.04 (95% CI, 0.83-1.35) in the underdosing group, compared with the standard apixaban dose group. The HAS-BLED score adjusted hazard ratio for any major bleeding was 1.66 (95% CI, 1.32-2.09) in the adjusted reduced dose group, and 1.51 (95% CI, 1.24-1.83) in the underdosing group, compared with apixaban in the standard dose group. Results were similar for major gastrointestinal bleeding and intracranial hemorrhage separately. We conclude that underdosing with apixaban is very common, and may not disproportionately elevate the risk of ischemic stroke. However, albeit halving the dose, patients treated with reduced apixaban dose (adjusted or underdosing) seem to be at higher risk for major bleeding.

FXI deficiency was not associated with an increased risk of pneumonia, pneumonia severity or short-term mortality among patients with pneumonia.

Introduction: Pneumococcus is a common bacterium that can cause serious infections, such as pneumonia, meningitis or blood stream infection in patients receiving immunosuppressive therapy. Infection by pneumococcus bacteria can be life-threatening leading to hospitalizations, complications and even death. In this work we have established a system base intervention that provides pneumococcal vaccine (Prevenar 13) for patients before starting chemotherapy and/or biological treatment. Methods: The intervention program included a set of measures: 1. Standard operating procedure (SOP) for vaccination of patients with hematological disorders. 2. Increasing the awareness of the medical and nursing staff regarding the importance of administering the vaccine before chemotherapy/biological treatments. 3. Purchasing vaccines by the hospital. 4.Coaching patients about the importance of receiving the vaccine before starting treatment. 5. Building a computerized record for monitoring and controlling the administration of the vaccine before starting treatment. 6. Transferring the information about the vaccine to the patient outpatient providers. 7. Documentation of the vaccine in the patient's electronic medical record. 8. Monthly review of new patients and vaccination before starting treatment. Results: In 2015, before intervention, only about 25% of patients were vaccinated appropriately against pneumococcus. With the start of the quality improvement project in April 2016, there was a gradual increase in the number of vaccinated patient before starting treatment. In December 2016, all new patients before starting treatment were properly vaccinated against pneumococcus. Although there was a significant increase in the number of patients at the institute in 2017 there was a 35% decrease in the number of patients hospitalized for pneumonia or sepsis compared to 2015. In addition, there was a 41% decrease in the number of hospitalizations with pneumonia or sepsis in the institute's patients. There was also a significant trend towards decrease in mortality (11% vs. 7%). Conclusions: The intervention program included: The creation of cooperation at several levels, medical, nursing and pharmacological that created cooperation between the medical center and the outpatient community clinics which led to the creation of a system that ensures that the patient will be vaccinated prior to starting immunosuppressive therapy. As a result of the intervention at the Institute and the data that was examined over 3 years, there has been a significant decrease in the rate of hospitalizations of patients due to pneumonia or sepsis. Disclosures No relevant conflicts of interest to declare.

ObjectiveClinical models such as the HAS-BLED (standing for Hypertension, Abnormal liver/renal function, Stroke history, Bleeding history or predisposition, Labile INR, Elderly, Drug/alcohol usage) were developed to predict risk of major bleeding on vitamin K antagonists/antiplatelet therapy. We aimed to develop a model that will improve the ability to predict major bleeding events in patients with non-valvular atrial fibrillation (AF) treated with new oral anticoagulants (NOACs).MethodsClalit Health Services is the largest of four integrated healthcare organisations in Israel, which insures 4.7 million patients (53% of the population). We identified in Clalit Health Services all patients with AF, new users of an NOAC (2013–2017), and followed them until first occurrence of a major bleeding event, death, switch to another oral anticoagulant, 30 days after discontinuation of NOAC or end of follow-up (31 December 2019). Importance of the candidate model variables was estimated by inclusion frequencies across forward selection algorithm applied to 50 bootstrap samples. Then, backward selection algorithm using the modified Bayesian Information Criterion for competing risks was applied to select predictors for the final model.Results47 623 patients with AF prescribed NOAC were studied. 28 055 patients with AF, initiators of apixaban (mean age 78.7, SD 9.0), were included in the first phase and had 662 major bleeding events. Nine variables were selected for inclusion in a final points-based risk-scoring system: male sex, anaemia, thrombocytopaenia (<99×103/µL), concurrent antiplatelet therapy, hypertension, prior major bleeding, risk factors for a fall, low cholesterol level and low estimated glomerular filtration rate, with apparent area-under-curve (AUC) of 0.6546. Applicability of the model was then shown for 14 118 and 5450 patients with AF, initiators of dabigatran and rivaroxaban, where the score achieved c indices of 0.62 and 0.61, respectively.ConclusionsWe present a novel and simple risk score for prediction of major bleeding in patients with non-valvular AF treated with NOACs. Validation in additional cohorts is warranted.