Predictors Of Bleeding Events Research Articles

Efficacy and Safety of Rivaroxaban, Apixaban, and Edoxaban for Nonvalvular Atrial Fibrillation Based on Blood Coagulation Activity and Drug Plasma Concentration: SETtsu and North Osaka Multicenter Direct Oral AntiCoagulant (SET DOAC) Registry

Background: The therapeutic effects of oral anticoagulant drugs for nonvalvular atrial fibrillation (NVAF) suggest that the three factor Xa (FXa) inhibitors may have distinct safety profiles, though this is not yet fully conclusive. This study investigated the current dosing of rivaroxaban, apixaban, and edoxaban by monitoring drug plasma concentration (PC) and coagulation activity from the viewpoint of the safety. Methods and results: This multicenter clinical study monitored the drug PC and two coagulation biomarkers (fibrinogen and fibrin monomer complex [FMC]) at peak and trough timing in 268 outpatients taking rivaroxaban (n = 72), apixaban (n = 71), and edoxaban (n = 125) for NVAF. Doses were adjusted based on the dose-adjustment criteria of each drug. Referencing our previous study, peak drug PC remained below the cut-off level for predicting bleeding events except in eight patients (rivaroxaban, n = 3; apixaban, n = 2; edoxaban, n = 3) in whom bleeding events occurred. Among them, two (one each on rivaroxaban and edoxaban) had a peak drug PC below the cut-off level. Drug PCs widely varied from peak to trough, whereas FMC levels, reflecting thrombin activity, remained within the normal range (<6.1 µg/mL) regardless of PC variations. These results indicated that the anticoagulant effects of these drugs persisted throughout the day regardless of the drug PC levels, dosage, and dosing frequency. Regarding the change over time in peak PC, the elevation over time developed more in rivaroxaban (29/57; 50.9%, p < 0.05) than in edoxaban (32/101; 31.7%), and rivaroxaban tended to accumulate more than edoxaban. Conclusions: Although drug PC levels of once-daily FXa inhibitors widely varied from peak to trough, FMC levels were maintained within the normal range without daily variations. Rivaroxaban also tended to accumulate over time. The results indicate the low risk of thrombotic events with once-daily FXa inhibitors and its correspondence to the twice-daily regimen.

Prevalence and Predictors of Bleeding Events in Patients with ESKD Who Have Autosomal Dominant Polycystic Kidney Disease: A National Database Analysis

Prevalence and Predictors of Bleeding Events in Patients with ESKD Who Have Autosomal Dominant Polycystic Kidney Disease: A National Database Analysis

Incidence of Arterial Thrombotic and Bleeding Events in Patients Who Develop Cancer after ST-elevation Myocardial Infarction.

Objective Cancers increase the risk of both arterial thrombosis and bleeding. The present study investigated whether or not comorbid new-onset cancers increase arterial thrombosis and bleeding events in patients after ST-elevation myocardial infarction (STEMI). Methods Among 918 consecutive STEMI patients, excluding 300 who used mechanical hemodynamic supportive devices, the 67 with cancer and 851 without cancer were compared with respect to the frequency of thrombotic events, consisting of myocardial infarction (MI) and ischemic stroke, and bleeding events during the trackable observation period in this observational study. The predictive accuracy for bleeding events evaluated by the Academic Research Consortium (ARC) high bleeding risk (HBR) criteria and the patients receiving stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score was assessed by C-statistics. Bleeding events were defined as type 3 or 5 according to the Bleeding Academic Research Consortium criteria. Results During the 1,233.3±1,284.4-day observation period, thrombotic events were observed in 13.4% of patients with cancer and 7.1% of patients without cancer (p=0.06; incidence rates, 2.4 vs. 2.4/100 person-years). MI and ischemic stroke were observed in 6.0% of patients with cancer and 3.5% of patients without cancer (p=0.23; incidence rates, 1.0 vs. 1.2/100 person-years) and 7.5% of patients with cancer and 3.6% of patients without cancer (p=0.18; incidence rates, 1.0 vs. 1.2/100 person-years), respectively. Bleeding events were observed in 26.9% of patients with cancer and 7.6% of patients without cancer (p<0.01; incidence rates, 4.4 vs. 2.4/100 person-years). The C-statistics for predicting bleeding events in patients with and without cancer were 0.65 vs. 0.71 using the ARC-HBR criteria and 0.67 vs. 0.71 using the PRECISE-DAPT scores, respectively. Conclusion Cancers increase unpredictable bleeding but not arterial thrombotic events in patients after STEMI.

Rotational Thromboelastometry and Clot Waveform Analysis as Point-of-Care Tests for Diagnosis of Disseminated Intravascular Coagulation in Critically Ill Children in Thailand.

This study aimed to determine the test performances of rotational thromboelastometry (ROTEM) and activated partial thromboplastin time-based clot waveform analysis (aPTT-CWA) compared with the International Society on Thrombosis and Hemostasis disseminated intravascular coagulation (ISTH-DIC) score for diagnosis of overt disseminated intravascular coagulation (ODIC) in critically ill children. Prognostic indicators of DIC complications were also evaluated. A prospective cross-sectional observational study was conducted. ROTEM and aPTT-CWA were assessed alongside standard parameters based on the ISTH-DIC score and natural anticoagulants. Both conventional and global hemostatic tests were repeated on days 3-5 for nonovert DIC. PICU of the Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. Infants and children who were admitted to PICU with underlying diseases predisposed to DIC, such as sepsis, malignancy, major surgery, trauma, or severe illness, were included in the study between July 1, 2021, and November 30, 2022. None. Sixty-four children were enrolled in this study. The prevalence of ODIC was 20.3%. Regarding ROTEM parameters, using EXTEM clot formation time (CFT) cutoff of greater than 102 seconds provided sensitivity and specificity of 90.9% and 80.9%, respectively, for diagnosing ODIC, with the area under the curve (AUC) of 0.86. In the case of aPTT-CWA performance, no biphasic waveform was observed, whereas both maximum coagulation acceleration (Min2) of less than 0.35%/s 2 and maximum coagulation deceleration of less than 0.25%/s 2 demonstrated identical sensitivities of 76.9% and specificities of 79.6%. Combining two global hemostatic tests significantly improved the diagnostic performance (INTEM CFT + EXTEM CFT + Min2 AUC 0.92 [95% CI, 0.80-1.00] vs. EXTEM CFT AUC 0.86 [95% CI, 0.75-0.96], p = 0.034). Bleeding was the most common consequence. In multivariable logistic regression analysis, Min2 of less than 0.36%/s 2 was an independent risk factor for bleeding complications, with an adjusted odds ratio of 15.08 (95% CI, 1.08-211.15, p = 0.044). ROTEM and aPTT-CWA were valuable diagnostic tools in critically ill children who might require point-of-care tests. Min2 showed significant clinical implications for predicting bleeding events in this population.

Activated Partial Thromboplastin Time (aPTT) as a Screening Test for Predicting Bleeding Manifestations in Adult Patients with Dengue Infection – A Diagnostic Accuracy Study

Abstract Background: Thrombocytopenia has been well established in dengue infections; however, coagulopathy is yet to be explored. Objective: The primary outcome was to assess derangement of activated partial thromboplastin time (aPTT) as a predictor of bleeding manifestations and severity of disease in dengue. Methods: This prospective cohort study included adults with dengue fever confirmed by serology, presenting to a single tertiary care center in South India. A structured questionnaire was used to extract clinical features and laboratory parameters at presentation, including aPTT. The patients were clinically observed during their course of illness for the outcomes of major and minor bleeding manifestations along with features of severe dengue. Results: Between May 2020 and September 2021, 140 patients were screened and 122 were recruited. Among these, 72 patients had normal aPTT and 50 had deranged aPTT. There were 41 bleeding events noted and 35 patients had severe dengue. There was a statistically significant correlation for aPTT derangement with major bleeding events (relative risk [RR] =4.03 [95% confidence interval (CI): 1.6–10.5]; P = 0.002), with minor bleeding events (RR = 2.52 [95% CI: 1.1–5.6]; P = 0.017) and with severity of dengue (RR = 3.14 [95% CI: 1.7–5.8); P &lt; 0.001]. aPTT had a good negative predictive value of 93.1% (95% CI: 84.5–97.7) for major bleeding. There was no statistically significant correlation between thrombocytopenia and bleeding manifestations. Conclusion: aPTT can be used as an indicator for predicting bleeding events and severity in dengue fever, with a good negative predictive value.

Nomogram for predicting bleeding events in nonvalvular atrial fibrillation patients receiving rivaroxaban: A retrospective study.

To construct a bleeding events prediction model of nonvalvular atrial fibrillation (NVAF) patients receiving rivaroxaban. We conducted a retrospective cohort study in patients with NVAF who received rivaroxaban from June 2017 to March 2019. Demographic information and clinical characteristics were obtained from the electronic medical system. Univariate analysis was used to find the primary predictive factors of bleeding events in patients receiving rivaroxaban. Multiple analysis was conducted to screen the primary independent predictive factors selected from the univariate analysis. Finally, the independent influencing factors were applied to build a prediction model by using R software; then, a nomogram was established according to the selected variables visually, and the sensitivity and specificity of the model was evaluated. Twelve primary predictive factors were selected by univariate analysis from 46 variables, and multivariate analysis showed that older age, higher prothrombin time (PT) values, history of heart failure and stroke were independent risk factors of bleeding events. The area under curve (AUC) for this novel nomogram model was 0.828 (95% CI: 0.763-0.894). The mean AUC over 10-fold stratified cross-validation was 0.787, and subgroup analysis validation also showed a satisfied AUC. In addition, the decision curve analysis showed that the PT in combination with CHA2DS2-VASc and HASBLED was more practical and accurate for predicting bleeding events than using CHA2DS2-VASc and HASBLED alone. PT in combination with CHA2DS2-VASc and HASBLED could be considered as a more practical and accurate method for predicting bleeding events in patients taking rivaroxaban.

Development of Bleeding Artificial Intelligence Detector (BLAIR) System for Robotic Radical Prostatectomy

Background: Addressing intraoperative bleeding remains a significant challenge in the field of robotic surgery. This research endeavors to pioneer a groundbreaking solution utilizing convolutional neural networks (CNNs). The objective is to establish a system capable of forecasting instances of intraoperative bleeding during robot-assisted radical prostatectomy (RARP) and promptly notify the surgeon about bleeding risks. Methods: To achieve this, a multi-task learning (MTL) CNN was introduced, leveraging a modified version of the U-Net architecture. The aim was to categorize video input as either “absence of blood accumulation” (0) or “presence of blood accumulation” (1). To facilitate seamless interaction with the neural networks, the Bleeding Artificial Intelligence-based Detector (BLAIR) software was created using the Python Keras API and built upon the PyQT framework. A subsequent clinical assessment of BLAIR’s efficacy was performed, comparing its bleeding identification performance against that of a urologist. Various perioperative variables were also gathered. For optimal MTL-CNN training parameterization, a multi-task loss function was adopted to enhance the accuracy of event detection by taking advantage of surgical tools’ semantic segmentation. Additionally, the Multiple Correspondence Analysis (MCA) approach was employed to assess software performance. Results: The MTL-CNN demonstrated a remarkable event recognition accuracy of 90.63%. When evaluating BLAIR’s predictive ability and its capacity to pre-warn surgeons of potential bleeding incidents, the density plot highlighted a striking similarity between BLAIR and human assessments. In fact, BLAIR exhibited a faster response. Notably, the MCA analysis revealed no discernible distinction between the software and human performance in accurately identifying instances of bleeding. Conclusion: The BLAIR software proved its competence by achieving over 90% accuracy in predicting bleeding events during RARP. This accomplishment underscores the potential of AI to assist surgeons during interventions. This study exemplifies the positive impact AI applications can have on surgical procedures.

Abstract 13192: Anti-Factor Xa Activity in Patients With Chronic Thromboembolic Pulmonary Disease With or Without Pulmonary Hypertension Treated With Factor Xa Inhibitors

Introduction and Hypothesis: Data on the efficacy and safety of factor Xa (FXa) inhibitors in chronic thromboembolic pulmonary disease (CTEPD) patients, especially in chronic thromboembolic pulmonary hypertension (CTEPH) patients, remain limited. Here, we aimed to evaluate the effect of FXa inhibitors by measuring anti-factor Xa activity (AXA) in both patients with CTEPD without pulmonary hypertension (PH) and CTEPH. Methods: Twenty-five CTEPD patients without PH and 52 CTEPH patients, treated with either of the FXa inhibitors were enrolled. AXA was measured by using HemosIL heparin calibrator. Blood samples were collected two times at the same day: immediately before the drug administration (trough) and 2-3 h after drug administration (peak). Results: In all 77 patients, median age was 66 (Interquartile range [IQR] 51–73) years, and 43% were male. In addition, 47% of the patients received rivaroxaban of 15 mg/day, 27% received apixaban of 10 mg/day, 14% received edoxaban of 60mg/day, and 12% received edoxaban of 30 mg/day. The median peak AXA of all 77 patients was 1.92 IU/mL and was comparable between CTEPD without PH and CTEPH patients. Significant difference of trough and peak AXA was shown among four different prescribed drugs (P &lt; .001 and P = .006, respectively). During the observational period of median 519 (IQR 364–1118) days, major and clinically relevant non-major bleeding occurred in six patients. ROC analysis to predict bleeding events revealed that the sensitivity and specificity of the cutoff point of a peak AXA of 2.1 IU/mL were 67% and 66%, respectively (AUC 0.66). The cumulative rate of major and clinically relevant non-major bleeding tended to be higher in patients with peak AXA ≥ 2.1 IU/mL than in patients with values below this point (p = .092, Figure). Conclusion: Measuring AXA could be a useful method to evaluate the effect of FXa inhibitors in CTEPD with or without PH patients.

IL-10 plus the EASIX score predict bleeding events after anti-CD19 CAR T-cell therapy.

Chimeric antigen receptor (CAR) T-cell-associated coagulopathy can cause bleeding events. To explore risk factors for hemorrhage after CAR T-cell therapy, we retrospectively analyzed routine indicators in 56 patients with non-Hodgkin lymphoma and B-cell acute lymphoblastic leukemia who received anti-CD19 CAR T-cell therapy. Disturbance of coagulation occurred mainly within one month post infusion, especially on day 7 and 14. The cumulative incidence of bleeding events within one month was 32.8%, with the median onset of 7 (range, 0-28) days. All bleeding events were grade 1-3. Patients who experienced bleeding events within one month had longer prothrombin time, higher IL-6, higher IL-10, and lower platelets before lymphodepletion. There were also correlations among coagulation-, inflammatory-, and tumor burden-related markers. Multi-variate analysis showed IL-10 (> 7.98 pg/mL; adjusted odds ratio [OR], 13.84; 95% confidence interval [CI], 2.03-94.36; P = 0.007) and the endothelial activation and stress index (EASIX, defined as dehydrogenase [U/L] × creatinine [mg/dL] / platelets [×109 cells/L]; >7.65; adjusted OR, 7.06; 95% CI, 1.03-48.23; P = 0.046) were significant risk factors for bleeding events. IL-10 plus the EASIX defined three risk groups for bleeding events with cumulative incidence of 100% (hazard ratio [HR], 14.47; 95% CI, 2.78-75.29; P < 0.0001), 38.5% (HR, 3.68; 95% CI, 0.82-16.67; P = 0.089), and 11.8% (reference), respectively. Future studies are needed to verify the risk assessment models for bleeding events after CAR T-cell treatment in larger cohorts.

XGBoost-based machine learning test improves the accuracy of hemorrhage prediction among geriatric patients with long-term administration of rivaroxaban

BackgroundHemorrhage is a potential and serious adverse drug reaction, especially for geriatric patients with long-term administration of rivaroxaban. It is essential to establish an effective model for predicting bleeding events, which could improve the safety of rivaroxaban use in clinical practice.MethodsThe hemorrhage information of 798 geriatric patients (over the age of 70 years) who needed long-term administration of rivaroxaban for anticoagulation therapy was constantly tracked and recorded through a well-established clinical follow-up system. Relying on the 27 collected clinical indicators of these patients, conventional logistic regression analysis, random forest and XGBoost-based machine learning approaches were applied to analyze the hemorrhagic risk factors and establish the corresponding prediction models. Furthermore, the performance of the models was tested and compared by the area under curve (AUC) of the receiver operating characteristic (ROC) curve.ResultsA total of 112 patients (14.0%) had bleeding adverse events after treatment with rivaroxaban for more than 3 months. Among them, 96 patients had gastrointestinal and intracranial hemorrhage during treatment, which accounted for 83.18% of the total hemorrhagic events. The logistic regression, random forest and XGBoost models were established with AUCs of 0.679, 0.672 and 0.776, respectively. The XGBoost model showed the best predictive performance in terms of discrimination, accuracy and calibration among all the models.ConclusionAn XGBoost-based model with good discrimination and accuracy was built to predict the hemorrhage risk of rivaroxaban, which will facilitate individualized treatment for geriatric patients.

P65: Predictors of Bleeding with Rotational Thromboelastometry in Patients with a Left Ventricular Assist Device

Purpose: Bleeding events are a significant source of morbidity and mortality in patients with left ventricular assist devices (LVAD). Rotational thromboelastometry (ROTEM) is a form of viscoelastographic testing that provides a real-time analysis of clot initiation, clot strength, and fibrinolysis. There is limited data regarding the use of ROTEM in predicting bleeding events in patients with LVADs post-implantation. Therefore, the purpose of this study is to determine if any component in ROTEM is associated with bleeding events in LVAD patients. Methods: This was a retrospective, single-centered, cohort study of LVAD patients implanted between January 2013 to December 2022 that compared ROTEM values between patients admitted due to bleeding and non-bleeding controls. ROTEM values drawn within 24 hours of separate hospitalizations were included. Patient encounters were excluded for the following reasons: ROTEM drawn after receiving blood or anticoagulant reversal agent, parenteral anticoagulation, or direct oral anticoagulants, and admission related to thrombotic events, index implantation, or device exchange. The primary outcome was to determine if ROTEM values were associated with bleeding events. Results: Of the 327 patient admissions evaluated, 266 patient encounters met inclusion criteria with 59 (22.2%) bleeding events and 207 (77.2%) controls. Of the excluded patients, 28 patients were excluded due to ROTEM drawn after receiving blood or an anticoagulant reversal agent. Baseline characteristics including age, gender, race, ethnicity, device type, last ejection fraction, and indication for implant were similar between groups. Patients admitted for a bleeding event were more likely to have a history of any bleeding event (p=0.01). There was no significant difference seen in the regression analysis evaluating INTEM clot time (p=0.55), INTEM clotting formation time (p=0.45), EXTEM clotting time (p=0.72), FIBTEM clot formation time (p=0.78), and FIBTEM clotting time (p=0.78) for patients experiencing a bleeding event vs those without a bleeding event (table 1). Conclusion: There are no differences in ROTEM values in LVAD patients admitted for bleeding events compared to non-bleeding admissions. Table 1.

Combination of Primary Hemostatic Disorders and Atrial Fibrillation Increases Bleeding Events Following Transcatheter Aortic Valve Replacement.

Background Patients with atrial fibrillation (AF) are likely to have a poor prognosis including bleedings following transcatheter aortic valve replacement (TAVR). Closure time of adenosine diphosphate (CT-ADP) is a primary hemostasis point-of-care test and is a predictor of bleeding events following TAVR. We aimed to evaluate the impact of ongoing primary hemostatic disorders on bleeding events in TAVR patients with AF. Methods We enrolled 878 patients from our prospective registry. The primary endpoint was VARC-2 major/life-threatening bleeding complications (MLBCs) at 1 year after TAVR and secondary endpoint was major adverse cardiac and cerebrovascular events (MACCEs) at 1 year, defined as a composite of all-cause death, myocardial infarction, stroke, and heart failure hospitalization. Ongoing primary hemostatic disorder was defined by a postprocedural CT-ADP >180 seconds. Results Patients with AF had a higher incidence of MLBCs (20 vs. 12%, p = 0.002), MACCE (29 vs. 20%, p = 0.002), and all-cause mortality (15 vs. 8%, p = 0.002) within 1 year compared to non-AF patients. When the cohort was split into four subgroups according to AF and CT-ADP >180 seconds, patients with AF and CT-ADP >180 seconds had the highest risk of MLBCs and MACCE. Multivariate Cox regression analysis confirmed that the patients with AF and CT-ADP >180 seconds had 3.9-fold higher risk of MLBCs, whereas those patients were no longer associated with MACCE after the adjustment. Conclusion In TAVR patients, AF with postprocedural CT-ADP >180 seconds was strongly associated with MLBCs following TAVR. Our study suggests that persistent primary hemostatic disorders contribute to a higher risk of bleeding events particularly in AF patients.

Safety and Efficacy Re-Evaluation of Edoxaban and Rivaroxaban Dosing With Plasma Concentration Monitoring in Non-Valvular Atrial Fibrillation: With Observations of On-Label and Off-Label Dosing.

Background: Off-label dosing of direct oral anticoagulants (DOAC) as a treatment for non-valvular atrial fibrillation (NVAF) is problematic. Here, we investigated the status of rivaroxaban and edoxaban dosing by monitoring plasma concentrations (PCs). Methods and Results: We monitored drug PCs in 391 and 333 outpatients receiving rivaroxaban and edoxaban, respectively, for NVAF. Drug doses were adjusted if the PC was above the cut-off value (rivaroxaban: 404 ng/mL; edoxaban: 402 ng/mL), determined from receiver operating characteristic curves for predicting bleeding events. On-label standard dosing was reduced to off-label underdosing due to high PCs above the cut-off more often for rivaroxaban (28.1%) than edoxaban (12.6%; P<0.001). Over a median follow-up of 13 months for rivaroxaban and 10 months for edoxaban, the annual incidence of bleeding events was higher with rivaroxaban than with edoxaban (4.88 vs. 3.73 patient-years; P<0.05), although no thromboembolic events occurred in either group. Furthermore, for patients with creatinine clearance >50 mL/min and body weight ≤60 kg, there was a greater incidence of bleeding events with rivaroxaban on-label 15 mg dosing than with edoxaban on-label 30 mg dosing (22.2% vs 2.9%; P<0.01). Conclusions: Monitoring the PCs of rivaroxaban and edoxaban in NVAF patients enables dose adjustments to reduce bleeding risk. The incidence of bleeding under drug PC monitoring was less in the edoxaban than rivaroxaban group.

To Measure or Not to Measure: Direct Oral Anticoagulant Laboratory Assay Monitoring in Clinical Practice.

The need for therapeutic drug monitoring of direct oral anticoagulants (DOACs) remains an area of clinical equipoise. Although routine monitoring may be unnecessary given predictable pharmacokinetics in most patients, there may be altered pharmacokinetics in those with end organ dysfunction, such as those with renal impairment, or with concomitant interacting medications, at extremes of body weight or age, or in those with thromboembolic events in atypical locations. We aimed to assess real-world practices in situations in which DOAC drug-level monitoring was used at a large academic medical center. A retrospective review of the records of patients who had a DOAC drug-specific activity level checked from 2016 to 2019 was included. A total of 119 patients had 144 DOAC measurements (apixaban (n = 62) and rivaroxaban (n = 57)). Drug-specific calibrated DOAC levels were within an expected therapeutic range for 110 levels(76%), with 21 levels (15%) above the expected range and 13 levels (9%) below the expected range. The DOAC levels were checked in the setting of an urgent or emergent procedure in 28 patients (24%), followed by renal failure in 17 patients (14%), a bleeding event in 11 patients (9%), concern for recurrent thromboembolism in 10 patients (8%), thrombophilia in 9 patients (8%), a history of recurrent thromboembolism in 6 patients (5%), extremes of body weight in 7 patients (5%), and unknown reasons in 7 patients (5%). Clinical decision making was infrequently affected by the DOAC monitoring. Therapeutic drug monitoring with DOACs may help predict bleeding events in elderly patients, those with impaired renal function, and in the event of an emergent or urgent procedure. Future studies are needed to target the select patient-specific scenarios where monitoring DOAC levels may impact clinical outcomes.

Predictors of bleeding events in acute decompensated heart failure patients with antithrombotic therapy: AURORA study.

Heart failure (HF) is reported to be one of the major risks of bleeding events. On the other hand, HF patients frequently receive anticoagulants or antiplatelet therapy to manage various co-morbidities. However, predictors of bleeding events in patients with HF have rarely been reported. This study aimed to evaluate the predictors of bleeding events and relationship between bleeding events and HF re-hospitalizations. We included 1660 acute decompensated heart failure (ADHF) patients from the AURORA registry between January 2015 and December 2020. A total of 1429 patients were excluded because of history of HF admission, missing echocardiographic data at discharge, lost to follow-up, haemodialysis and no antithrombotic drugs. Finally, we evaluated 231 patients from AURORA registry. The bleeding events were defined as Type 2 to 5 bleeding according to the Bleeding Academic Research Consortium definition. We divided our patients into the bleeding group and non-bleeding group. We compared the baseline characteristics, medications, laboratory data, and echocardiographic data between the two groups. Median age was 78 (IQR 71-82) years old and male accounted for 59%. Approximately half of the patients had an antiplatelet therapy and 70% had an anticoagulant therapy. During a median follow-up of 651 (IQR 357-1139) days, 32 patients (13.8%) suffered from bleeding events. The major driver of the registered events was gastrointestinal bleeding (n=21, 65.6%), and the other events were cerebral bleeding (n=4, 12.5%), intraarticular bleeding (n=2, 6.3%), urogenital bleeding (n=2, 6.3%), haemorrhagic pericardial effusions (n=1, 3.1%), subcutaneous hematomas (n=1, 3.1%), and haemothorax (n=1, 3.1%). There was a significantly lower haemoglobin level (P<0.01), higher proportion of inferior vena cava (IVC) diameter ≥21mm (P<0.01), and higher furosemide equivalent doses per kilogram (P<0.01) in the bleeding group than non-bleeding group. A multivariate analysis revealed an equivalent dose of furosemide per kilogram ≥0.66mg/kg (hazard ratios (HR) of 2.64, 95% confidence interval (CI) 1.26-5.68, P=0.01), haemoglobin ≤10.3g/dL (HR of 2.43, 95% CI 1.14-5.03, P=0.02), and IVC diameter ≥21mm (HR of 2.79, 95% CI 1.16-6.29, P=0.02) were independently associated with bleeding events. The Kaplan-Meier analysis showed that HF re-hospitalization rates were higher in the bleeding group than non-bleeding group (P=0.04). High doses of oral loop diuretics, IVC dilatation, and anaemia were predictors of bleeding events in patients hospitalized with ADHF patients. In addition, bleeding events were associated with HF re-hospitalizations.

Stroke risk scores for prediction of mortality and hemorrhages in atrial fibrillation patients

Background: Atrial fibrillation (AF) is an emerging epidemic worldwide, responsible for a twofold increase in mortality, independent of other risk factors. Stroke prevention is the cornerstone of AF management. However, oral anticoagulation imposes an increased risk of bleeding. Several risk scores have been developed for estimating both the thromboembolic and the bleeding risks. The aim of the study was to determine the usefulness of different stroke risk scores as predictors of mortality and hemorrhagic events in AF patients. Methods: We retrospectively enrolled 211 AF patients hospitalized in the Cardiology Ward of our tertiary hospital. The primary endpoints were mortality and non-minor bleeding events. The mean follow-up period was 378 days for bleeding events and 5 years and 1 month for mortality. For each patient, we evaluated the following stroke risk scores: CHADS2, CHA2DS2-VASc, R2CHADS2, ABC, ATRIA, GARFIELD. Results: The mean age in our cohort is 66, with a slight predominance of women (52.2%). For a CHA2DS2-VASc ≥ 4 as well as for a score of 2-3, 5-year survival was worse than for patients with a score of 0-1(chi-squared=8.13; p=0.01). Similarly, all subgroups of patients with an ABC <2%, had a worse 5-year survival when compared with an ABC score of ≥2% (chi-squared=12.85; p=0.005). C-statistics show a modest predictive value for mortality, for all stroke scores except Garfield, with similar AUCs, the highest being for CHA2DS2-VASc (AUC 0.656; p=0.0001). CHA2DS2-VASc also correlates with bleeding events, having a good predictive ability (AUC 0.723; 95%CI 0.658-0.782, p=0.001), mildly superior to HAS-BLED (AUC 0.674; 95% CI 0.523-0.825; p = 0.04) and very close to Garfield-bleeding (0.765; 95%CI 0.702-0.80; p=0.0001). Conclusions: CHA2DS2-VASc is comparable to HAS-BLED and Garfield-bleeding in predicting bleeding events in AF patients. CHA2DS2-VASc and ABC correlate directly and consistently with mortality rate. For CHA2DS2-VASc, the AUCs for our endpoints are similar to the ones for stroke prediction, highlighting the potential of extending its applicability to various outcomes.

Empiric Anticoagulation Therapy in Hospitalized COVID-19 Patients: An Evaluation of Bleeding Risk Scores Performances in Predicting Bleeding Events.

Currently, there is no standardized consensus on anticoagulation (AC) among patients with coronavirus disease (COVID-19), which has an overwhelming bleeding risk. We aimed to compare the patterns of AC in COVID-19 patients and compare two validated risk scores in predicting bleeding events. A retrospective review of medical records was conducted for COVID-19 patients who received empiric anticoagulation therapy. The primary outcomes included bleeding events, survival, and mechanical ventilation needs. We applied the HAS-BLED and ORBIT bleeding risk scores to assess the predictive accuracy, using c-statistics and the receiver operating curve (ROC) method. Of the included patients (n = 921), with a mean age of 58.1 ± 13.2, 51.6% received therapeutic AC and 48.4% received a prophylactic AC dose. Significantly higher values of d-dimer and C-reactive protein (CRP) among the therapeutic AC users (p < 0.001) were noted with a significantly prolonged duration of hospital stay and mechanical ventilation (p < 0.001 and p = 0.011, respectively). The mean value of the HAS-BLED and ORBIT scores were 2.53 ± 0.93 and 2.26 ± 1.29, respectively. The difference between the two tested scores for major bleeding and clinically relevant non-major bleeding was significant (p = 0.026 and 0.036, respectively) with modest bleeding predictive performances. The therapeutic AC was associated with an increased risk of bleeding. HAS-BLED showed greater accuracy than ORBIT in bleeding risk predictability.

Bleeding and thrombotic complications in patients with severe COVID-19: A prospective observational study.

Bleeding and thrombotic complications in patients with severe COVID-19: A prospective observational study.

Association between ticagrelor plasma concentration and bleeding events in Chinese patients with acute coronary syndrome.

The risk of ticagrelor-related bleeding events remains a major clinical concern, especially in East Asian populations. Previous studies have reported higher ticagrelor exposure in Asian patients than in Caucasians. This prompted us to investigate the correlation between ticagrelor concentrations and bleeding events. Patients diagnosed with acute coronary syndrome and receiving dual antiplatelet therapy (aspirin and ticagrelor) were enrolled and followed up for 12 months. Trough plasma concentrations of ticagrelor and a major active metabolite were assayed, and 10 single nucleotide polymorphisms associated with ticagrelor pharmacokinetics and safety were also identified. A total of 631 patients were included and 133 patients had bleeding academic research consortium type 1 or 2 bleeding event. The median ticagrelor concentration (interquartile range) was significantly higher in patients with bleeding events than that in patients without bleeding events (322.6ng/mL [196.2-458.0ng/mL] vs. 222.1ng/mL [140.4-341.9ng/mL], P< .001). According to the receiver operating characteristic curve, the cut-off value for ticagrelor levels predicting bleeding events was 363.3ng/mL (area under the curve = 0.65; P< .001, 95% Cl: 0.595-0.700). Pharmacogenomics results showed that P2Y12 (rs6787801, P = .024) and P2Y12 (rs6785930, P = .048) were statistically associated with ticagrelor levels and bleeding events, respectively. Ticagrelor plasma concentrations were associated with bleeding events in Chinese patients with acute coronary syndrome.

Revised HAS-BLED score for bleeding prediction in atrial fibrillation patients with oral anticoagulants.

BackgroundThere were several limitations to the original HAS‐BLED (oHAS‐BLED) score in patients with atrial fibrillation (AF). This trial studied the revised HAS‐BLED (rHAS‐BLED) score for predicting bleeding events in anticoagulated AF patients.MethodsThis study retrospectively recruited anticoagulated AF patients in the Central Chest Institute of Thailand between 2014 and 2021. The rHAS‐BLED score was oHAS‐BLED using the estimated glomerular filtration rate of <60 ml/min/1.73 m2 for abnormal renal function, SAMe‐TT2R2 score of ≥3 for labile INR, and adding clinically relevant nonmajor bleeding (CRNMB) into bleeding history. The outcome was major bleeding (MB) and/or CRNMB at 1‐year follow‐up visit. The outcome between both groups was compared by using the chi‐square test or Fisher's exact test. Receiver‐operating characteristics curve was used to analyze the discrimination performances of both scores and the results were illustrated by using c‐statistics.ResultsA total of 256 anticoagulated AF patients were enrolled. The average age was 73.6 ± 10.1 years. The average oHAS‐BLED and rHAS‐BLED scores were 1.7 ± 0.9 and 2.6 ± 1.2, respectively. Twenty patients in rHAS‐BLED ≥3 (15.9%) and 9 patients in rHAS‐BLED <3 (6.9%) experienced MB and/or CRNMB. The rHAS‐BLED score of ≥3 increased the bleeding risk with statistical significance (OR 2.54, 95% CI 1.11–5.81, p = .04). The discriminative performance of the rHAS‐BLED score was illustrated with c‐statistics of 0.61 (95% CI 0.50–0.71).ConclusionsThe rHAS‐BLED score could predict bleeding events in anticoagulated AF patients. However, a larger study is needed to confirm these results in the future.