Factor XI deficiency is associated with lower risk for cardiovascular and venous thromboembolism events.

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 = 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 = 0.26 (95% CI, 0.08-0.84). In summary, factor XI deficiency is associated with decreased incidence of cardiovascular events and VTE.

Novel bleeding prediction model in atrial fibrillation patients on new oral anticoagulants.

OBJECTIVE: Clinical 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). METHODS: Clalit 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. RESULTS: 47 623 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. CONCLUSIONS: We 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.

Stroke and Bleeding Risks in Patients with Atrial Fibrillation Treated with Reduced Apixaban Dose: A Real-Life Study.

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.

Association of factor V activity with risk of venous thromboembolism and atherothrombotic cardiovascular events: A retrospective population-based cohort study.

INTRODUCTION: Factor V (FV) deficiency is a rare inherited coagulation disorder associated with bleeding tendency. As a result, it has been postulated that decreased FV activity may confer protection against venous thromboembolism and atherothrombotic cardiovascular events. MATERIALS AND METHODS: Using the electronic database of the largest health care provider in Israel, we identified all adult individuals who were tested for FV activity between January 2004 and June 2017. Subjects with liver cirrhosis or FV Leiden mutation were excluded. FV activity was classified into three predefined categories; FV activity >50%, FV activity 30-50%, and FV activity ≤30%. Patients were followed from January 2004 to June 2017 for new atherothrombotic cardiovascular events (composite of myocardial infarction, stroke, and TIA) and venous thromboembolism (VTE). RESULTS: Overall 2021 individuals were included; 83.2% had FV activity >50%, 9.6% FV activity 30-50%, and 7.2% had FV activity ≤30%. Compared to individuals with FV activity >50% the adjusted HR for atherothrombotic cardiovascular events was 1.10 (95% CI, 0.63-1.90) in those with FV activity 30-50%, and 0.95 (0.49-1.8) in those with FV activity ≤30%. None of the patients with FV activity 30-50% had VTE during follow-up; therefore those with FV activity ≤50% were classified into one group. VTE incidence was lower in those with FV activity ≤50% compared to those with FV >50% activity; adjusted HR = 0.28 (0.09-0.91). CONCLUSION: This study suggests that decreased FV activity might be associated with decreased incidence of VTE. No significant association appears to exist between FV activity and atherothrombotic cardiovascular events.