Independent Predictors Of Bleeding Research Articles

Highest 3-month international normalized ratio (INR): a predictor of bleeding following ultrasound-guided liver biopsy.

To determine whether international normalized ratio (INR), bilirubin, and creatinine predict bleeding risk following percutaneous liver biopsy. A total of 870 consecutive patients (age 53 ± 14years; 53% (459/870) male) undergoing non-targeted, ultrasound-guided, percutaneous liver biopsy at a single tertiary center from 01/2016 to 12/2019 were retrospectively reviewed. Results were analyzed using descriptive statistics and logistic regression models to evaluate the relationship between individual and combined laboratory values, and post-biopsy bleeding risk. Receiver operating characteristic (ROC) curves and area under ROC (AUC) curves were constructed to evaluate predictive ability. Post-biopsy bleeding occurred in 2.0% (17/870) of patients, with 0.8% (7/870) requiring intervention. The highest INR within 3months preceding biopsy demonstrated the best predictive ability for post-biopsy bleeding and was superior to the most recent INR (AUC = 0.79 vs 0.61, p = 0.003). Total bilirubin is an independent predictor of bleeding (AUC = 0.73) and better than the most recent INR (0.61). Multivariate regression analysis of the highest INR and total bilirubin together yielded no improvement in predictive performance compared to INR alone (0.80 vs 0.79). The MELD score calculated using the highest INR (AUC = 0.79) and most recent INR (AUC = 0.74) were similar in their predictive performance. Creatinine is a poor predictor of bleeding (AUC = 0.61). Threshold analyses demonstrate an INR of > 1.8 to have the highest predictive accuracy for bleeding. The highest INR in 3months preceding ultrasound-guided percutaneous liver biopsy is associated with, and a better predictor for, post-procedural bleeding than the most recent INR and should be considered in patient risk stratification. Despite correction of coagulopathic indices, the highest international normalized ratio within the 3months preceding percutaneous liver biopsy is associated with, and a better predictor for, bleeding and should considered in clinical decision-making and determining biopsy approach. • Bleeding occurred in 2% of patients following ultrasound-guided liver biopsy, and was non-trivial in 41% of those patients who needed additional intervention and had an associated 23% 30-day mortality rate. • The highest INR within 3months preceding biopsy (AUC = 0.79) is a better predictor of bleeding than the most recent INR (AUC = 0.61). • The MELD score is associated with post-procedural bleeding, but with variable predictive performance largely driven by its individual laboratory components.

Clinical outcomes in patients with atrial fibrillation and a history of falls using non-vitamin K antagonist oral anticoagulants: A nationwide cohort study

BackgroundData on non-vitamin K antagonist oral anticoagulant (NOAC) use in patients with atrial fibrillation (AF) and a history of falls are limited. Therefore, we investigated the impact of a history of falls on AF-related outcomes, and the benefit-risk profiles of NOACs in patients with a history of falls. MethodsUsing Belgian nationwide data, AF patients initiating anticoagulation between 2013 and 2019 were included. Previous falls that occurred ≤ 1 year before anticoagulant initiation were identified. ResultsAmong 254,478 AF patients, 18,947 (7.4%) subjects had a history of falls, which was associated with higher risks of all-cause mortality (adjusted hazard ratio (aHR) 1.11, 95%CI (1.06–1.15)), major bleeding (aHR 1.07, 95%CI (1.01–1.14)), intracranial bleeding (aHR 1.30, 95%CI (1.16–1.47)) and new falls (aHR 1.63, 95%CI (1.55–1.71)), but not with thromboembolism. Among subjects with a history of falls, NOACs were associated with lower risks of stroke or systemic embolism (aHR 0.70, 95%CI (0.57–0.87)), ischemic stroke (aHR 0.59, 95%CI (0.45–0.77)) and all-cause mortality (aHR 0.83, 95%CI (0.75–0.92)) compared to vitamin K antagonists (VKAs), while major, intracranial, and gastrointestinal bleeding risks were not significantly different. Major bleeding risks were significantly lower with apixaban (aHR 0.77, 95%CI (0.63–0.94)), but similar with other NOACs compared to VKAs. Apixaban was associated with lower major bleeding risks compared to dabigatran (aHR 0.78, 95%CI (0.62–0.98)), rivaroxaban (aHR 0.78, 95%CI (0.68–0.91)) and edoxaban (aHR 0.74, 95%CI (0.59–0.92)), but mortality risks were higher compared to dabigatran and edoxaban. ConclusionsA history of falls was an independent predictor of bleeding and death. NOACs had better benefit-risk profiles than VKAs in patients with a history of falls, especially apixaban.

Abstract Number ‐ 171: Stroke location as predictor of bleeding after EVT for ischemic stroke in the anterior circulation

Introduction Hemorrhage is a known risk of Endovascular thrombectomy (EVT) for ischemic stroke . Several predictors of bleeding have been identified. However, stroke location has not yet been evaluated as an independent predictor. Methods Patients ≥ 18 years who underwent EVT for anterior circulation large vessel occlusion between January 1, 2020, and December 31, 2021, at our centre were included. After the exclusion criteria, a total of 344patients were analyzed. The admission CT scans were reviewed by a neuroradiologist to determine the ASPECTS, and classify the involved regions into location groups: only central core, only cortical, and both central and cortical areas. Post EVT images were evaluated to assign the Heidelberg bleeding classification. Statistical analysis was performed in R, version 4.1. For univariate analyses, Fisher’s exact or chi‐square test was used for categorical data. Quantitative data were tested for normality, and the t‐test or Mann‐Whitney test was applied accordingly. All variables in the univariate analyses with p < 0.15 were considered for the stepwise logistic regression models. Results Patients had a median age of 73 years (IQR 20), NIHSS of 16 (IQR 9),ASPECTS of 7 (IQR 3), systolic blood pressure of 146 mmHg (IQR 25), and glycemia of 7 mmol/L (IQR 2). The most frequent occlusion site was M1 (65.7%), and most patients had an mTICI > 2A (89.5%). Bleeding occurred in 182 (52.9%) and intraparenchymal hematoma in 73 (21.2%) patients, with most bleeding only in the central core (65.4%), with the lentiform nucleus involved in 122 (67%) of the bleeds. Thirty‐eight patients died (11%), and 237 had a modified Rankin score > 2 at discharge (68.9%). Stroke location was significant for all types of bleeding (p < 0.001) and intraparenchymal hematoma (p = 0.137) in the univariate analyses. However, after multiple logistic regression, the stroke location was not an independent predictor of any type of bleeding. On the other hand, a lower ASPECTS was a significant predictor of all types of bleeding (p < 0.001; OR 1.347; 95% CI 1.1799 ‐ 1.539) and intraparenchymal hematoma (p = 0.009; OR 1.756; 95% CI 1.152 ‐ 2.677). In addition to ASPECTS, high NIHSS (p = 0.038; OR 1.058; 95% CI 1.003 ‐ 1.115) was a significant predictor of all types of bleeding, while high systolic blood pressure (p = 0.027; OR 1. 037;95% CI 1.004 ‐ 1.071), cardioembolic stroke (p = 0.042; OR 10.408; 95% CI 1.085 ‐ 99.889), and poor collaterals (p = 0.046; OR 5.068; 95% CI 1.029 ‐ 24.951) were significant for intraparenchymal hematoma. Conclusions Stroke location is not an independent predictor of bleeding. However, stroke size, as indicated by the ASPECT, is a predictor of bleeding after EVT. Moreover, some modifiable predictors were not significant because they are already controlled for in the study, but systolic pressure was a significant predictor of intraparenchymal hematoma and shows that more studies are needed to determine the appropriate control levels to reduce the chance of bleeding without compromising cerebral perfusion.

A Longitudinal Study of Thrombosis and Bleeding Outcomes With Thromboprophylaxis in Pregnant Women at Intermediate and High Risk of VTE.

The efficacy and safety of thromboprophylaxis in pregnancy at intermediate to high risk of venous thrombo-embolism (VTE) is an area of ongoing research. This study aimed to assess thrombosis and bleeding outcomes associated with thromboprophylaxis in women at risk of VTE. A cohort of 129 pregnancies, who received thromboprophylaxis for the prevention of VTE, were identified from a specialist obstetric clinic in Johannesburg, South Africa. Intermediate-risk pregnancies, with medical comorbidities or multiple low risks, were managed with fixed low-dose enoxaparin antepartum and for a median (interquartile range) of 4 (4) weeks postpartum. High-risk pregnancies, with a history of previous VTE, were managed with anti-Xa adjusted enoxaparin antepartum and for a median of 6 (0) weeks postpartum. Pregnancy-related VTE was objectively confirmed. Major bleeding, clinically relevant nonmajor bleeding (CRNMB) and minor bleeding were defined according to the International Society on Thrombosis and Hemostasis Scientific Subcommittee. Venous thrombo-embolism occurred antepartum in 1.4% (95% CI: 0.04-7.7) of intermediate and 3.4% (95% CI: 0.4-11.7) of high-risk pregnancies. Bleeding events occurred in 7.1% (95% CI: 2.4-15.9) of intermediate and 8.5% (95% CI: 2.8-18.7) of high-risk pregnancies. Of these bleeding events, 3.1% (95% CI: 1.0-8.0) were classified as major bleeding. On univariate analysis, no independent predictors of bleeding were identified. The rates of thrombosis and bleeding in this predominantly African population were consistent with similar studies and can be used to inform pregnant women of the benefits of anticoagulation and the risks of potential bleeding.

Long-term Risk of Bleeding and Ischemic Events After Ischemic Stroke or Transient Ischemic Attack in Young Adults.

Guidelines recommend antithrombotic medication as secondary prevention for patients with ischemic stroke or transient ischemic attack (TIA) at young age based on results from trials in older patients. We investigated the long-term risk of bleeding and ischemic events in young patients after ischemic stroke or TIA. We included 30-day survivors of first-ever ischemic stroke or TIA aged 18-50 years from the Follow-Up of TIA and Stroke Patients and Unelucidated Risk Factor Evaluation (FUTURE) study, a prospective cohort study of stroke at young age. We obtained information on recurrent ischemia based on structured data collection from 1995 until 2014 as part of the FUTURE study follow-up, complemented with information on any bleeding and ischemic events by retrospective chart review from baseline until last medical consultation or June 2020. Primary outcome was any bleeding; secondary outcome any ischemic event during follow-up. Both were stratified for sex, age, etiology, and use of antithrombotic medication at discharge. Bleeding and ischemic events were classified according to location and bleeding events also by severity. We included 544 patients (56.1% women, median age of 42.2; interquartile range [IQR] 36.5-46.7 years) with a median follow-up of 9.6 (IQR 2.5-14.3) years. Ten-year cumulative risk of any bleeding event was 21.8% (95% CI 17.4-26.0) and 33.9% (95% CI 28.3-37.5) of any ischemic event. Risk of bleeding was higher in women with a cumulative risk of 28.2% (95% CI 21.6-34.3) vs 13.7% (95% CI 8.2-18.9) in men (p < 0.01), mainly because of gynecologic bleeds. Female sex (p < 0.001) and age between 40 and 49 years (p = 0.04) were independent predictors of bleeding. Young patients after ischemic stroke or TIA have a substantial long-term risk of both bleeding (especially women) and ischemic events. Future studies should investigate the effects of long-term antithrombotics in young patients, taking into account the risk of bleeding complications.

Incidence of bleeding and thromboembolism and impact on overall survival in adult patients with hemophagocytic lymphohistiocytosis: A 20‐year provincial retrospective cohort study

BackgroundHemophagocytic lymphohistiocytosis (HLH) is a rare syndrome characterized by uncontrolled immune activation and high risk of death. There is scarce data on the incidence of bleeding and thromboembolism in HLH. ObjectivesTo determine the cumulative incidence of bleeding and thromboembolism and impact on survival in adults with HLH. Patients/MethodsWe conducted a multicenter retrospective cohort study of adults with HLH in Alberta, Canada (1999–2019). The cumulative incidence of bleeding and thromboembolism were calculated, accounting for competing risks. Cox proportional hazards models were used to assess the impact of bleeding and thromboembolism on overall survival (OS). ResultsWe identified 97 adults with HLH (median age 46 years). Venous thromboembolism (VTE) occurred in 11 (11%) patients at a median of 9 days from admission. ISTH major bleeding and clinically relevant non‐major bleeding occurred in 39 (40%) patients, at a median of 16 days after admission. Nadir platelet count (adjusted odds ratio [aOR] 1.8 per log decrease, 95% confidence interval [CI] 1.2–2.8) and mechanical ventilation (aOR 4.9, 95% CI 1.8–14.8) were independent predictors of bleeding on multivariable analysis. Adjusting for competing risks, the 90‐day cumulative incidences of bleeding and thromboembolism were 39% and 13%, respectively. The median OS was 18.8 months. VTE, but not bleeding, was significantly associated with adverse OS (adjusted hazard ratio 2.5, 95% CI 1.1–5.7). ConclusionsIn adults with HLH, VTE appears more common than previously described and is a predictor of mortality, although this may be due to unadjusted confounding. VTE prevention and treatment are challenging due to high bleeding rates.

Incidence and Predictors of Bleeding in Patients With Cancer and Atrial Fibrillation

Despite patients with cancer having a higher incidence of atrial fibrillation (AF), little is known about the predictors of outcomes in this population. This study aimed to assess the incidence and predictors of bleeding in patients with AF and cancer. The study population comprised 16,056 patients from a Spanish health area diagnosed with AF between 2014 and 2018 (1,137 with cancer). Competing risk analysis were used to evaluate the association of cancer and bleeding. Discrimination and calibration of bleeding risk scores were assessed by the concordance statistic and the Brier score, respectively. During a median follow-up of 4.9 years, the incidence of bleeding in patients with cancer was 13.2 per 100 patients/year. After multivariate adjustment, a significant association between cancer and bleeding was detected (subdistribution hazard ratio [sHR] 1.18, 95% CI 1.07 to 1.30, p=0.001), specifically in patients with active cancer or previous radiotherapy. Early age, male gender, diabetes, and anticoagulation were independent predictors of bleeding. However, only anticoagulation with vitamin K antagonist (sHR 1.36, 95% CI 1.03 to 1.78, p=0.026), not with direct oral anticoagulants (sHR 1.25, 95% CI 0.84 to 1.85, p=0.270), was associated with bleeding. Discrimination and calibration of Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, and Drugs/alcohol concomitantly (HAS-BLED), AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA), and Hepatic or renal disease, Ethanol abuse, Malignancy, Older (age ≥75 years), Reduced platelet count or function, Rebleeding risk, Hypertension, Anaemia, Genetic factors, Excessive fall risk and Stroke (HEMORR2HAGES) scores were poor in patients with cancer (concordance statistic <0.6 and Brier score >0.1). In summary, cancer was associated with an increased risk of bleeding in patients with AF. The predictive ability of bleeding risk scores was poor in this population. Anticoagulation with vitamin K antagonist but not with direct oral anticoagulants, was an independent predictor of bleeding in patients with cancer.

Prophylactic cyanoacrylate injection for gastric extension of esophageal varices: a randomized controlled trial

Aim of the studyGastric variceal bleeding is more severe and fatal than esophageal bleeding. Injection of cyanoacrylate into bleeding gastric varices is recommended, but prophylactic injection is debatable. Aim of this study is to evaluate prophylactic cyanoacrylate injection into gastric extension of esophageal varices type 2 (GOV2).Material and methodsThis randomized controlled trial included 75 patients (3 groups) with risky or bleeding esophageal varices and non-bleeding GOV2. Group A received a cyanoacrylate GOV2 injection, esophageal variceal band ligation (EBL), and β-blocker (BB); group B received EBL and BB; and group C received EBL. Follow-up for ≥ 24 weeks to check for bleeding or death was performed.ResultsBaseline variables were comparable among the 3 groups. During follow-up (median, 37.5 weeks), increasing gastric extension and or bleeding risk signs were significantly lower in group A (0%) than B (12%) and C (32%) (p < 0.001). Bleeding occurred more in groups B (24%) and C (24%) than in A (8%) (p = 0.2). Gastric extension size was an independent predictor of bleeding (p = 0.03). Portal hypertensive gastropathy (PHG) decreased in groups A (24%) and B (24%) more than in C (8%) (p = 0.5). Mortality rates were 0.0% in group A, 8% in B, and 4% in C (p = 0.2).ConclusionsProphylactic cyanoacrylate injection into GOV2 before EBL significantly decreased the varix size and risk signs for bleeding with a statistically insignificant tendency to decrease the bleeding rate. A large gastric extension was an independent predictor of bleeding. Adding β-blockers can potentially decrease PHG and bleeding risk. An independent study with a larger sample size is recommended to confirm the rate of bleeding and test the mortality difference.

Age-adjusted risk factors are independently associated with an increased risk of major bleeding during the two-year follow-up of the ETNA-AF-Europe registry

Abstract Background Non-vitamin K antagonist oral anticoagulants (NOACs) are a preferred treatment option over warfarin for anticoagulation in patients with atrial fibrillation (AF). Management decisions for thromboprophylaxis in AF need to balance the risk of stroke against the risk of bleeding. Various patient characteristics have been identified as independent risk factors for bleeding. A substantial number of bleeding events might be prevented if independent predictors of bleeding were identified. Purpose The present analysis aims at assessing age-adjusted risk predictors of major bleeding during two-year follow-up of unselected European patients with AF in the ETNA-AF-Europe registry. Methods ETNA-AF-Europe is a prospective, multi-centre, post-authorisation, observational study conducted in 825 centres enrolling patients treated with edoxaban once daily in 10 European countries. Wald Chi square tested the association between risk predictors and major bleeding after adjusting for age, given that age is a well-known, strong predictor of anticoagulation-related bleeding in patients with AF. Results Overall, 13,417 patients with AF (edoxaban 60 mg: n=10,248; edoxaban 30 mg: n=3169) completed the two-year follow-up. The mean age was 73.6±9.5 years, with ∼84% of the patients aged over 65 years. Mean CHA2DS2-VASc and HAS-BLED scores were 3.2 and 2.5, respectively. 438 (3.3%) patients had a history of bleeding events at baseline, of which 138 (1.0%) had a history of major bleeding event. Univariate analysis demonstrated that recalculated glomerular filtration rate (Cockcroft-Gault Equation) (GFR-CG) at baseline was the strongest age-adjusted predictor of major bleeding (Wald Chi-Square: 31.84; p&amp;lt;0.0001) (Figures 1 and 2), followed by history of major or clinically relevant non-major (CRNM) bleeding (24.08; p&amp;lt;0.0001), HAS-BLED score (21.10; p&amp;lt;0.0001), history of heart failure (derived) (16.59; p&amp;lt;0.0001), subjective frailty as assessed by physician (17.35; p=0.0002), history of major bleeding (14.14; p=0.0002), chronic obstructive pulmonary disease (COPD) (12.84; p=0.0003), CHA2DS2-VASc (12.14; p=0.0005), history of myocardial infarction (MI) (7.79; p=0.005), and left ventricular ejection fraction (LVEF) categorised by 40% (5.45; p=0.02). Conclusion Bleeding events on therapy with edoxaban can be predicted by quantifying kidney disease and capturing information on heart failure, frailty, prior bleeding, chronic obstructive lung disease and history of myocardial infarction. These data highlight the need for optimal management of anticoagulation therapy and close follow-up of patients with such risk profiles. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH Figure 1. GFR-CG as a predictor of major bleedingFigure 2. Predictors of major bleeding

The bleeding risk treatment paradox at the physician and hospital level: Implications for reducing bleeding in patients undergoing percutaneous coronary intervention

Bleeding is a common and costly complication of percutaneous coronary intervention (PCI). Bleeding avoidance strategies (BAS) are used paradoxically less in patients at high-risk of bleeding: "bleeding risk-treatment paradox" (RTP). We determined whether hospitals and physicians, who do not align BAS to PCI patients' bleeding risk (ie, exhibit a RTP) have higher bleeding rates. We examined 28,005 PCIs from the National Cardiovascular Data Registry CathPCI Registry for 7 hospitals comprising BJC HealthCare. BAS included transradial intervention, bivalirudin, and vascular closure devices. Patients' predicted bleeding risk was based on National Cardiovascular Data Registry CathPCI bleeding model and categorized as low (<2.0%), moderate (2.0%-6.4%), or high (≥6.5%) risk tertiles. BAS use was considered risk-concordant if: at least 1 BAS was used for moderate risk; 2 BAS were used for high risk and bivalirudin or vascular closure devices were not used for low risk. Absence of risk-concordant BAS use was defined as RTP. We analyzed inter-hospital and inter-physician variation in RTP, and the association of RTP with post-PCI bleeding. Amongst 28,005 patients undergoing PCI by 103 physicians at 7 hospitals, RTP was observed in 12,035 (43%) patients. RTP was independently associated with a higher likelihood of bleeding even after adjusting for predicted bleeding risk, mortality risk and potential sources of variation (OR 1.66, 95% CI 1.44-1.92, P < .001). A higher prevalence of RTP strongly and independently correlated with worse bleeding rates, both at the physician-level (Wilk's Lambda 0.9502, F-value 17.21, P < .0001) and the hospital-level (Wilk's Lambda 0.9899, F-value 35.68, P < .0001). All the results were similar in a subset of PCIs conducted since 2015 - a period more reflective of the contemporary practice. Bleeding RTP is a strong, independent predictor of bleeding. It exists at the level of physicians and hospitals: those with a higher rate of RTP had worse bleeding rates. These findings not only underscore the importance of recognizing bleeding risk upfront and using BAS in a risk-aligned manner, but also inform and motivate national efforts to reduce PCI-related bleeding.

ADP-induced platelet reactivity and bleeding events in patients with acute myocardial infarction complicated by cardiogenic shock

While previous reports showed ADP-induced platelet reactivity to be an independent predictor of bleeding after PCI in stable patients, this has never been investigated in patients with cardiogenic shock. The association of bleeding events with respect to ADP-induced platelet aggregation was investigated in patients undergoing primary PCI for acute myocardial infarction complicated by cardiogenic shock and with available on-treatment ADP-induced platelet aggregation measurements. Out of 233 patients, 74 suffered from a severe BARC3 or higher bleed. ADP-induced platelet aggregation was significantly lower in patients with BARC≥3 bleedings (p < .001). Multivariate analysis identified on-treatment ADP-induced platelet aggregation as an independent risk factor for bleeding (HR = 0.968 per AU). An optimal cutoff value of <12 AU for ADP-induced platelet aggregation to predict BARC≥3 bleedings was identified via ROC analysis. Moreover, the use of VA-ECMO (HR 1.972) or coaxial left ventricular pump (HR 2.593), first lactate (HR 1.093 per mmol/l) and thrombocyte count (HR 0.994 per G/l) were independent predictors of BARC≥3 bleedings. In conclusion, lower on-treatment ADP-induced platelet aggregation was independently associated with severe bleeding events in patients with AMI-CS. The value of platelet function testing for bleeding risk prediction and guidance of anti-thrombotic treatment in cardiogenic shock warrants further investigation.

ADP-induced platelet reactivity and bleeding events in patients with acute myocardial infarction complicated by cardiogenic shock

Abstract Funding Acknowledgements Type of funding sources: None. Background While previous reports showed ADP-induced platelet reactivity to be an independent predictor of bleeding after PCI in stable patients, this has never been investigated in patients with cardiogenic shock (CS). Methods The association of bleeding events with respect to ADP-induced platelet aggregation was investigated in patients undergoing primary PCI for acute myocardial infarction complicated by cardiogenic shock (AMI-CS) and with available on-treatment ADP-induced platelet aggregation measurements. Results Out of 233 patients, 74 suffered from a severe BARC 3 or higher bleed. ADP-induced platelet aggregation was significantly lower in patients with BARC≥3 bleedings (10 AU [IQR 3 - 13] vs. 15 AU [IQR 9 - 25], p &amp;lt; 0.001). Multivariate analysis identified on-treatment ADP-induced platelet aggregation as an independent risk factor for bleeding (HR = 0.968 per AU, 95% confidence interval (CI) 0.942-0.994). An optimal cut-off value of &amp;lt;12 AU for ADP-induced platelet aggregation to predict BARC≥3 bleedings was identified via ROC analysis. Moreover, use of VA-ECMO (HR 1.972, 95% CI 1.003-3.879) or coaxial left ventricular pump (HR 2.593, 95% CI 1.509-4.455), first lactate (HR 1.093 per mmol/l, 95% CI 1.037-1.152) and thrombocyte count (HR 0.994 per G/l, 95% CI 0.990-0.998) were independent predictors of BARC≥3 bleedings. There was no significant difference in survival nor ischemic events between patients with low and high on-treatment platelet reactivity. Conclusion: Lower on-treatment ADP-induced platelet aggregation was independently associated with severe bleeding events in patients with AMI-CS. The value of platelet function testing for bleeding risk prediction and guidance of anti-thrombotic treatment in CS warrants further investigation.

Stress ulcer prophylaxis for critically ill children: routine use needs to be re-examined

IntroductionStress ulcer prophylaxis (SUP) is commonly used in Paediatric Intensive Care Units (PICUs). However, strong evidence for this practice is lacking and there is a dire need for paediatric randomized controlled trials (RCTs). Our aim was to assess the usefulness of SUP with omeprazole in critically ill children. Patients and methodsWe conducted a randomized, controlled open-label trial, including 144 children admitted into a PICU with a paediatric Sequential Organ Failure Assessment (pSOFA) score of less than 16. We randomly allocated patients to SUP with omeprazole or no SUP. The primary outcome was development of upper gastrointestinal bleeding or nosocomial infection. ResultsThe incidence of gastrointestinal bleeding was 27.1%, but clinically significant bleeding developed in only 5.6% of patients. We did not find a significant difference in the incidence of bleeding between the prophylaxis and control groups (27.8% vs 26.4%; P = .85). We also did not find a significant difference between the groups in the incidence of ventilator-associated pneumonia (VAP) (9.6% vs 8.3%; P = .77). The incidence of central line-associated bloodstream infection (CLABSI) was higher in the prophylaxis group compared to the control group (30.6% vs 12.5%; P = .014). None of the patients developed Clostridium difficile-associated diarrhoea. We did not find significant differences in mortality, length of PICU stay or duration of mechanical ventilation. Mechanical ventilation was an independent predictor of bleeding (OR, 6.4; 95%CI, 2.73–14.9). ConclusionIn PICU patients with mild to moderate organ dysfunction, omeprazole does not seem to be useful for prevention of gastrointestinal bleeding while at the same time increasing the risk of CLABSI. Thus, we recommend restricting SUP to mechanically ventilated children.

Profilaxis de las úlceras de estrés en niños críticos: necesidad de replantear su uso rutinario

IntroductionStress ulcer prophylaxis (SUP) is commonly used in Paediatric Intensive Care Units (PICUs). However, strong evidence for this practice is lacking and there is a dire need for paediatric randomized controlled trials (RCTs). Our aim was to assess the usefulness of SUP with omeprazole in critically ill children. Patients and methodsWe conducted a randomized, controlled open-label trial, including 144 children admitted into a PICU with a paediatric Sequential Organ Failure Assessment (pSOFA) score of less than 16. We randomly allocated patients to SUP with omeprazole or no SUP. The primary outcome was development of upper gastrointestinal bleeding or nosocomial infection. ResultsThe incidence of gastrointestinal bleeding was 27.1%, but clinically significant bleeding developed in only 5.6% of patients. We did not find a significant difference in the incidence of bleeding between the prophylaxis and control groups (27.8 vs. 26.4%; p = 0.85). We also did not find a significant difference between the group in the incidence of ventilator-associated pneumonia (VAP) (9.6 vs. 8.3%; p = 0.77). The incidence of central line-associated bloodstream infection (CLABSI) was higher in the prophylaxis group compared to the control group (30.6% vs. 12.5%; p = 0.014). None of the patients developed Clostridium difficile-associated diarrhoea. We did not find significant differences in mortality, length of PICU stay or duration of mechanical ventilation. Mechanical ventilation was an independent predictor of bleeding (OR 6.4; 95% CI, 2.73-14.9). ConclusionIn PICU patients with mild to moderate organ dysfunction, omeprazole does not seem to be useful for prevention of gastrointestinal bleeding while at the same time increasing the risk of CLABSI. Thus, we recommend restricting SUP to mechanically ventilated children.

Predictors, Type, and Impact of Bleeding on the Net Clinical Benefit of Long‐Term Ticagrelor in Stable Patients With Prior Myocardial Infarction

BackgroundTicagrelor reduces ischemic risk but increases bleeding in patients with prior myocardial infarction. Identification of patients at lower bleeding risk is important in selecting patients who are likely to derive more favorable outcomes versus risk from this strategy.Methods and ResultsPEGASUS‐TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin—Thrombolysis in Myocardial Infarction 54) randomized 21 162 patients with prior myocardial infarction in a 1:1:1 fashion to ticagrelor 60 mg or 90 mg twice daily or placebo, with ticagrelor 60 mg approved for long‐term use. TIMI major or minor bleeding was the primary end point for this analysis. Causes of bleeding were categorized by site and etiology, and independent predictors were identified. At 3 years, ticagrelor 60 mg increased the rate of TIMI major or minor bleeding by 2.0% versus placebo (1.4% placebo versus 3.4% ticagrelor). The bleeding excess was driven primarily by spontaneous gastrointestinal bleeds. A history of spontaneous bleeding requiring hospitalization and the presence of anemia were independent predictors of bleeding but not of ischemic risk. Patients with at least 1 risk predictor had 3‐fold higher rates of bleeding with ticagrelor 60 mg versus those who had neither (absolute risk increase, 4.4% versus 1.5%; P=0.01). Patients with neither predictor had a more favorable benefit profile with ticagrelor 60 mg versus placebo including lower mortality (hazard ratio, 0.79; 95% CI, 0.65–0.96; P interaction = 0.03).ConclusionsIn patients with prior myocardial infarction, bleeding with ticagrelor 60 mg twice daily is predominantly spontaneous gastrointestinal. A history of spontaneous bleeding requiring hospitalization or the presence of anemia identifies patients at higher risk of bleeding, and the absence of either identifies patients likely to have a more favorable net benefit with ticagrelor.RegistrationURL https://www.clinicaltrials.gov/. Unique identifier: NCT01225562.

Efficacy and safety of single high-dose versus double high-dose intracoronary bolus tirofiban in patients with ST-segment elevation myocardial infarction

Objectives: We evaluated the efficacy and safety of single high-dose versus double high-dose intracoronary bolus tirofiban in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: A total of 80 patients, who were admitted to our clinic and underwent primary PCI, were included in this observational cohort study. The patients were divided into the single high-dose group (n = 40) and the double high-dose group (n = 40) according to the intracoronary bolus tirofiban regime. The primary endpoint was assumed as the incidence of major adverse cardiac event (s) (MACE) defined as all-cause mortality and repeat coronary revascularization (target vessel revascularization [TVR]) at 30 days. MACE and bleeding events were evaluated at 7 and 30 days. Results: The primary endpoint was not significantly different between the single and the double high-dose groups (40.0% vs. 17.5%, p = 0.994). However, a significantly lower 30-day TVR rate was observed in the double high-dose group (27.5% vs. 7.5%, p = 0.019). No significant difference was observed in terms of 30-day all-cause mortality between the two groups (12.5% vs. 10.0%, p = 0.712). Major bleeding events were not observed in any group. Multivariate logistic regression analysis demonstrated that CRUSADE score (Hazard ratio [HR]: 5.721; 95% CI: 2.036 to 16.073, p = 0.001) and platelet count (HR: 1.009; 95% CI: 1.000 to 1.018, p = 0.048) were the independent predictors of bleeding at 7 days. Conclusions: Double high-dose intracoronary bolus tirofiban in STEMI patients undergoing primary PCI was associated with significantly lower 30-day TVR rates without an increase in bleeding events. However, it did not significantly affect MACE and all-cause mortality rates.

Bleeding After Elective Interventional Endoscopic Procedures in a Large Cohort of Patients With Cirrhosis.

INTRODUCTION:Elective therapeutic endoscopy is an important component of care of cirrhotic patients, but there are concerns regarding the risk of bleeding. This study examined the incidence, risk factors, and outcomes of bleeding after endoscopic variceal ligation (EVL), colonoscopic polypectomy, and endoscopic retrograde cholangiopancreatography with sphincterotomy in cirrhotic patients.METHODS:A cohort study of patients with cirrhosis who underwent the above procedures at a single center between 2012 and 2014 was performed. Patients with active bleeding at the time of procedure were excluded. Patients were followed for 30 days to assess for postprocedural bleeding and for 90 days for mortality.RESULTS:A total of 1,324 procedures were performed in 857 patients (886 upper endoscopies, 358 colonoscopies, and 80 endoscopic retrograde cholangiopancreatograpies). After EVL, bleeding occurred in 2.8%; after polypectomy, bleeding occurred in 2.0%; and after sphincterotomy, bleeding occurred in 3.8%. Independent predictors of bleeding after EVL and polypectomy included younger age and lower hemoglobin. For EVL, bleeding was also associated with infection and model for end-stage liver disease-Na. International normalized ratio was associated with bleeding in univariate analysis only, and platelet count was not associated with bleeding in any procedure. Bleeding after EVL was associated with 29% 90-day mortality, and bleeding after polypectomy was associated with 14% mortality. Of the 3 patients with postsphincterotomy bleeding, none were outliers regarding their baseline characteristics.DISCUSSION:In patients with cirrhosis, bleeding occurs infrequently after elective therapeutic endoscopy and is associated with younger age, lower hemoglobin, and high mortality. Consideration of these risk factors may guide appropriate timing and preprocedural management to optimize outcomes.

Creatine kinase is associated with bleeding after myocardial infarction

BackgroundThe ADP-scavenging enzyme creatine kinase (CK) is reported to reduce ADP-dependent platelet activation. Therefore, we studied whether highly elevated CK after ST-elevation myocardial infarction (STEMI) is associated with bleeding.MethodsData of...

Predictors of Bleeding in the Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study

Introduction In the Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study a simplified, standardized, pharmacokinetic based perioperative interruption scheme was stablished for patients with non-valvular atrial fibrillation taking direct oral anticoagulants (DOACs). The rate of bleeding and thromboembolic outcomes was low, yet better awareness of bleeding predictors will aid the informed decision making for both clinicians and patients. Thus, we aimed to define the factors associated with perioperative bleeding events in the PAUSE cohorts. Methods The standardized interruption scheme is depicted in figure 1. We analyzed bleeding as the composite of major and clinically relevant non-major bleeding (MB/CRNM) according to the ISTH criteria. Putative predictors of bleeding were prospectively collected during the PAUSE recruitment. For patients taking dabigatran the dilute thrombin time was measured from a pre-operative blood sample. A DOAC-calibrated anti-factor Xa level was assessed preoperatively for patients taking factor Xa inhibitors. Continuous numeric variables were reported as means with SD; frequencies were reported when appropriate. We used stratified logistic regression models for analysis. All statistical analyses were performed in R version 3.6.0. Results There were 3007 patients requiring perioperative DOAC interruption, distributed in the apixaban (A) (N = 1,257), dabigatran (D) (N = 668), and rivaroxaban (R) (N = 1,082) cohorts. Characteristics of the patients who developed MB/CRNM are reported in table 1. More than one third of included patients underwent a high bleeding risk procedure. The rates of MB/CRNM were 3.02% in group A, 2.84% in group D, and 4.16% of group R patients from the point of DOAC interruption to 30 days after the procedure. In the univariate analysis, surgery bleeding risk was significantly associated with MB/CRNM (low vs high, OR 0.56, 95% CI 0.36-0.86; p=0.008). Multivariate analysis stratified by region found hypertension (OR 1.81, 95%CI 1.07-3.07; p=0.027), prior bleed or bleed predisposition (OR 1.62, 95% CI 1.02-2.58; p=0.043) were significantly associated with MB/CRNM (table 2); whereas surgery bleeding risk was not significant after adjusting other covariates. Female gender was associated with lower MB/CRNM risk (This result seems to be mainly driven by the rate of CRNM, 2.21% male had CRNM and 1.57% female had CRNM, and the signal disappeared in the model for MB). [Hypertension (OR 3.93, 95%CI 1.40-11.07; p=0.010), active cancer (OR 2.30, 95% CI 1.10-4.81; p=0.026) were significantly associated with MB (table 3)] Aspirin use was more prevalent among males (13.78%) than females (7.75%), but this did not fully explain the gender effect. The model for MB/CRNM had an area under the curve (AUC) of 0.65 (standard error 0.03). Drug level analysis was available for 2541 (84.5%) patients. In the stratified analysis with the DOAC level (&amp;gt;50ng/dL vs £50ng/dL) as a single predictor, there was no significant association with MB/CRNM observed (OR 1.07, 95% CI 0.38-2.96; p=0.902). In the multivariate model, adding DOAC level to the model did not improve the AUC. Discussion A standardized interruption scheme results in low risk of bleeding for patients with atrial fibrillation interrupting DOACs for surgery/invasive procedures. The protocol-defined surgical bleed risk in PAUSE was valid, and selected to numerically higher bleeding rates, but it was not independent predictor of bleeding when the interruption scheme and covariates are accounted for. Hypertension was the only potentially modifiable predictor of perioperative MB/CRNM bleeding. Likely selecting for a frail population, active cancer and hypertension were predictors of MB events. In the exploratory analyses, residual levels did not improve the predictive model. The multivariate model had a low performance and we do not advocate modification of the PAUSE-proposed interruption schema based on these results. The PAUSE trial is the first large scale study enabled to investigate the factors governing perioperative bleed among DOAC-Anticoagulated patients. Nonetheless, we did not have power to analyze DOAC cohorts independently due to the paucity outcomes. Overall, the results strengthen the validity of the PAUSE-proposed DOAC interruption scheme for atrial fibrillation patients who need surgery. Disclosures Tafur: Recovery Force: Consultancy; Janssen: Other: Educational Grants, Research Funding; BMS: Research Funding; Idorsia: Research Funding; Daichi Sanyo: Research Funding; Stago: Research Funding; Doasense: Research Funding. Spyropoulos:Bayer: Consultancy; Ingelheim: Consultancy; Portola: Consultancy; Janssen: Research Funding; Boehringer INgelheim: Research Funding; Janssen: Consultancy. Douketis:Pfizer: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Leo Pharma: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Portola: Other: Consultant ; Janssen: Other: Consultant ; The Merck Manual: Patents &amp; Royalties; Up-to-Date: Patents &amp; Royalties.

Valvular Resistance and Bleeding Events Among Patients Undergoing Transcatheter Aortic Valve Replacement

ABSTRACT Background: Aortic valvular resistance (VR) may be a surrogate for shear stress in patients with aortic stenosis. Stenosis-induced shear stress is known to affect platelet function and bleeding tendency. The aim of this study is to assess the association between VR and bleeding events in patients undergoing transcatheter aortic valve replacement (TAVR). Methods: VR was calculated in 708 patients undergoing TAVR between August 2007 and December 2015. All subjects were stratified into a high VR (HVR; ≥238 dynes·cm−5) and a low VR (LVR; <238) group according to the median of VR. The primary endpoint was bleeding within 1 year after TAVR. Results: After adjustment for confounding factors, patients with HVR had a higher risk of bleeding events at 1 year (HRadj 2.09, 95% CI 1.56–2.80) than those with LVR. The difference emerged within the first month after intervention (HRadj 2.20, 95% CI 1.62–2.99) and was driven by procedural (HRadj 1.82, 95% CI 1.33–2.72) and non-procedural (HRadj 1.86, 95% CI 1.15–3.00) bleeding events. The effect was consistent across access sites and valve types. Of note, the unfavorable effect with regard to bleeding attenuated beyond 30 days post-TAVR (HR 1.01, 95% CI 0.32–3.14). In a multivariable analysis, HVR, renal failure at baseline, transapical approach, and moderate or greater post-TAVR aortic regurgitation were identified as independent predictors of bleeding within 1 year after TAVR. Conclusions: HVR at baseline was associated with bleeding events after TAVR; however, bleeding tendency in this setting improved within 30 days after releasing stenosis at the aortic position. Abbreviations: AR, aortic regurgitation; AS, aortic stenosis; AVA, aortic valve area; CI, confidence interval; MACCE, major adverse cardiac and cerebrovascular events; NYHA, New York Heart Association; RHC, right heart catheterization; TAVR, transcatheter aortic valve replacement; VARC, the Valve Academic Research Consortium; VR, valvular resistance