Search

Background: Fatal bleeding is a component of the primary safety outcome in most studies evaluating anticoagulation for venous thromboembolism (VTE), but a standardized definition for fatal bleeding is lacking. Objectives: To summarize definitions of fatal bleeding and describe the range of case-fatality rates of major bleeding in VTE studies. Methods: MEDLINE, Embase, and CENTRAL databases were searched from January 2008 to July 2021 for prospective studies that enrolled patients with VTE and evaluated the efficacy/safety of anticoagulation for VTE treatment or included fatal or major bleeding as primary outcome. Two authors independently performed study selection and data extraction. The primary outcome was the definition of fatal bleeding. The secondary outcome was the case-fatality rate of major bleeding. Data were analyzed using descriptive statistics. Results: Of 4911 records identified, we included 132 articles representing 89 distinct studies. Twenty-seven (20%) articles and 7 of 89 (8%) studies reported a definition of fatal bleeding. Overall, we identified 3 different types of definitions that were either on the basis of a specific time interval between bleeding and death, bleeding location (intracranial) or clinical presentation (hemodynamic deterioration), or mainly relied on the judgment of the adjudication committee to determine the cause of death. The case-fatality rate of major bleeding ranged from 0 to 60% (median, 9.1%; interquartile range, 2.8%-18%). Conclusion: Less than 10% of studies assessing anticoagulant treatment for VTE reported a definition for fatal bleeding. The lack of a (standardized) definition for fatal bleeding may lead to inaccurate estimates of the risk of fatal bleeding, particularly when compared across studies.

Gastrointestinal (GI) bleeding is the most frequent single site of oral anticoagulant (OAC)-associated major bleeding. Patients with major GI bleeding experience morbidity and a substantial risk of short-term all-cause mortality up to 10%. While OACs are frequently discontinued during acute bleeding, there is substantial uncertainty about whether, when, and how OACs should be resumed after bleeding has resolved. Limited evidence suggests a lower risk of thromboembolism and death, and a higher risk of recurrent bleeding with OAC resumption. However, the absolute risks and optimal timing of anticoagulation remain uncertain based on these observational studies at risk of bias, particularly due to baseline confounding. In addition to an individualized approach to determining the benefits and harms of treatment decisions informed by the best available evidence about thrombosis and recurrent bleeding, discussions should meaningfully incorporate patient values and preferences. The objective of this review is to provide a framework for decision-making by summarizing the epidemiology and clinical outcomes of OAC-associated GI bleeding, providing an approach for assessment and risk stratification for OAC resumption and its timing, and outlining strategies for the prevention of recurrent GI bleeding.

Background: COVID-19–related acute illness is associated with an increased risk of venous thromboembolism (VTE). Objective: These evidence-based guidelines from the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation in patients with COVID-19. Methods: ASH formed a multidisciplinary guideline panel that included patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process and performed systematic evidence reviews (through November 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess evidence and make recommendations, which were subject to public comment. This is an update to guidelines published in February 2021 as part of the living phase of these guidelines. Results: The panel made one additional recommendation. The panel issued a conditional recommendation in favor of therapeutic-intensity over prophylactic-intensity anticoagulation in patients with COVID-19–related acute illness who do not have suspected or confirmed VTE. The panel emphasized the need for an individualized assessment of risk of thrombosis and bleeding. The panel also noted that heparin (unfractionated or low molecular weight) may be preferred because of a preponderance of evidence with this class of anticoagulants. Conclusion: This conditional recommendation was based on very low certainty in the evidence, underscoring the need for additional, high-quality, randomized controlled trials comparing different intensities of anticoagulation in patients with COVID-19–related acute illness.

Background: COVID-19–related critical illness is associated with an increased risk of venous thromboembolism (VTE). Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for patients with COVID-19. Methods: ASH formed a multidisciplinary guideline panel, including 3 patient representatives, and applied strategies to minimize potential bias from conflicts of interest. The McMaster University Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process, including performing systematic evidence reviews (up to January 2022). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the GRADE approach to assess evidence and make recommendations, which were subject to public comment. This is an update to guidelines published in February 2021 and May 2021 as part of the living phase of these guidelines. Results: The panel made 1 additional recommendation: a conditional recommendation for the use of prophylactic-intensity over therapeutic-intensity anticoagulation for patients with COVID-19–related critical illness who do not have suspected or confirmed VTE. The panel emphasized the need for an individualized assessment of thrombotic and bleeding risk. Conclusions: This conditional recommendation was based on very low certainty in the evidence, underscoring the need for additional, high-quality, randomized controlled trials comparing different intensities of anticoagulation for patients with COVID-19–related critical illness.

International audience; Patients with acute venous thromboembolism (VTE) require anticoagulant therapy to prevent recurrent VTE and death, which exposes them to an inherent increased risk of bleeding. Identification of patients at high risk of bleeding, and mitigating this risk, is an essential component of the immediate and long-term therapeutic management of VTE. The bleeding risk can be estimated by either implicit judgment, weighing individual predictors (clinical variables or biomarkers), or by risk prediction tools developed for this purpose. Management of bleeding risk in clinical practice is, however, far from standardized. International guidelines are contradictory and lack clear and consistent guidance on the optimal management of bleeding risk. This report of the ISTH subcommittee on Predictive and Diagnostic Variables in Thrombotic Disease summarizes the evidence on the prediction of bleeding in VTE patients. We systematically searched the literature and identified 34 original studies evaluating either predictors or risk prediction models for prediction of bleeding risk on anticoagulation in VTE patients. Based on this evidence, we provide recommendations for the standardized management of bleeding risk in VTE patients.

Background Data on resuming oral anticoagulants (OACs) after bleeding are primarily from studies involving patients given warfarin, with few data on direct OACs (DOACs). We aimed to characterize prescribing patterns for OACs after OAC-related bleeding and compare the rates of bleeding, thrombosis and mortality in patients who resumed either type of OAC with those who did not. Methods We conducted a population-based cohort study of adults aged 66 years or older who were admitted to hospital for bleeding while receiving OACs from Apr. 1, 2012, to Mar. 31, 2017, using linked administrative health databases from Ontario. We used competing risk methods to calculate cause-specific adjusted hazard ratios (HRs) for thrombosis, bleeding and mortality with resumption of OACs adjusted as a time-varying covariate. We determined time to OAC resumption using the Kaplan-Meier method. Results We included 6793 patients with gastrointestinal (n = 4297, 63.3%), intracranial (n = 805, 11.9%) or other bleeding (n = 1691, 25.0%). At cohort entry, 3874 patients (57.0%) were prescribed warfarin and 2919 patients (43.0%) were prescribed a DOAC. The most common indication for OAC was atrial fibrillation (n = 5557, 81.8%), followed by venous thromboembolism (n = 1367, 20.1%). Oral anticoagulants were resumed in 4792 patients (70.5%) within 365 days of the index bleed. The median time to resumption was 46 (interquartile range 6-550) days. We found that resuming OAC was associated with reduced rates of thrombosis (adjusted HR 0.60, 95% confidence interval [CI] 0.50-0.72) and mortality (adjusted HR 0.54, 95% CI 0.48-0.60), and an increased rate of rebleeding (adjusted HR 1.88, 95% CI 1.64-2.17). Interpretation We found that resuming OAC is associated with a reduction in thrombosis and mortality but an increase in bleeding. Randomized controlled trials that evaluate the net benefit of strategies for resumption of OAC after a bleeding event are warranted.

Background We aimed to establish diagnostic criteria for bleeding independently associated with mortality after noncardiac surgery (BIMS) defined as bleeding during or within 30 days after noncardiac surgery that is independently associated with mortality within 30 days of surgery, and to estimate the proportion of 30-day postoperative mortality potentially attributable to BIMS. Methods This was a prospective cohort study of participants ≥45 yr old having inpatient noncardiac surgery at 12 academic hospitals in eight countries between 2007 and 2011. Cox proportional hazards models evaluated the adjusted relationship between candidate diagnostic criteria for BIMS and all-cause mortality within 30 days of surgery. Results Of 16 079 participants, 2.0% (315) died and 36.1% (5810) met predefined screening criteria for bleeding. Based on independent association with 30-day mortality, BIMS was identified as bleeding leading to a postoperative haemoglobin Conclusions Bleeding independently associated with mortality after noncardiac surgery (BIMS), defined as bleeding that leads to a postoperative haemoglobin Clinical trial registration NCT00512109.

Key Points This toolkit contains standardized customizable thrombosis-related data elements for incorporation into COVID-19 studies. Standardization can enhance the quality of data collection, create efficiency, and facilitate comparison of results and pooling of data sets., Thrombosis has emerged as an important complication of coronavirus disease 2019 (COVID-19), particularly among individuals with severe illness. However, the precise incidence of thrombotic events remains uncertain due to differences in study design, patient populations, outcome ascertainment, event definitions, and reporting. In an effort to overcome some of these challenges and promote standardized data collection and reporting in clinical studies, the American Society of Hematology Research Collaborative COVID-19 Non-Malignant Hematology Task Force, in collaboration with the International Society on Thrombosis and Haemostasis COVID-19 Task Force, developed sets of data elements in the following domains: venous thromboembolism, myocardial infarction, stroke/transient ischemic attack, peripheral arterial thrombosis, bleeding, laboratory investigations, and antithrombotic therapy. Data elements in each of these domains were developed with 3 levels of detail to facilitate their incorporation into studies evaluating a range of interventions and outcomes. Previously published data elements were included where possible. The use of standardized variables in a range of clinical studies can enhance the quality of data collection, create efficiency, enhance comparison of results across studies, and facilitate future pooling of data sets., Visual Abstract

Iron deficiency is a common consequence of bariatric surgery and frequently leads to anemia. Our study reports the incidence and predictors of iron deficiency, iron deficiency anemia (IDA), and IV iron use after bariatric surgery. We conducted a retrospective study of all adult patients who underwent bariatric surgery from January to December 2012 at the regional bariatric surgery center in Hamilton, Ontario, Canada, and were followed for at least 6 months. Time-to-event data were presented as Kaplan-Meier curves. Cox regression analysis was used to identify outcome predictors. A total of 388 patients met the inclusion criteria. Iron deficiency, IDA, and the use of IV iron were reported in 43%, 16%, and 6% of patients, respectively, with a mean follow-up of 31 months. The cumulative incidence of iron deficiency and IDA increased with longer follow-up, and there was a significant increase in IV iron use starting 3 years after surgery. Malabsorptive procedures (hazard ratio [HR], 1.92; 95% confidence interval [CI], 1.20-3.06; P = .006) and low baseline ferritin (HR, 0.96; 95% CI, 0.95-0.97; P < .001) were associated with an increased risk of iron deficiency. Young age (HR, 0.90; 95% CI, 0.82-0.99; P = .028), baseline anemia (HR, 19.6; 95% CI, 7.85-48.9; P < .001), and low baseline ferritin (HR, 0.96; 95% CI, 0.95-0.98; P < .001) were associated with an increased risk of IDA. Our results suggest that IDA is a delayed consequence of bariatric surgery and that preoperative assessment of patient risk may be possible.

Ty J. Gluckman, MD, FACC, Chair Niti R. Aggarwal, MD, FACC Nicole M. Bhave, MD, FACC Gregory J. Dehmer, MD, MACC Olivia N. Gilbert, MD, MSc, FACC Chayakrit Krittanawong, MD Dharam J. Kumbhani, MD, SM, FACC Javier A. Sala-Mercado, MD, PhD Andrea L. Price, CPHQ, RCIS, AACC David E.

Aims To examine the rates of venous thromboembolism (VTE) in high-income, upper middle-income, and lower middle/low-income countries (World Bank Classification). Methods and results We examined the rates of VTE in high-income, upper middle-income, and lower middle/low-income countries (World Bank Classification) in a cohort derived from four prospective international studies (PURE, HOPE-3, ORIGIN, and COMPASS). The primary outcome was a composite of pulmonary embolism, deep vein thrombosis, and thrombophlebitis. We calculated age- and sex-standardized incidence rates (per 1000 person-years) and used a Cox frailty model adjusted for covariates to examine associations between the incidence of VTE and country income level. A total of 215 307 individuals (1.5 million person-years of follow-up) from high-income (n = 60 403), upper middle-income (n = 42 066), and lower middle/low-income (n = 112 838) countries were included. The age- and sex-standardized incidence rates of VTE per 1000 person-years in high-, upper middle-, and lower middle/low-income countries were 0.87, 0.25, and 0.06, respectively. After adjusting for age, body mass index (BMI), smoking, antiplatelet therapy, anticoagulant therapy, education level, ethnicity, and incident cancer diagnosis or hospitalization, individuals from high-income and upper middle-income countries had a significantly higher risk of VTE than those from lower middle/low-income countries [hazard ratio (HR) 3.57, 95% confidence interval (CI) 2.40–5.30 and HR 2.27, 95% CI 1.59–3.23, respectively]. The effect of country income level on VTE risk was markedly stronger in people with a lower BMI, hypertension, diabetes, non-White ethnicity, and higher education. Conclusion The rates of VTE are substantially higher in high-income than in low-income countries. The factors underlying the increased VTE risk in higher-income countries remain unknown.

BackgroundCOVID-19–related acute illness is associated with an increased risk of venous thromboembolism (VTE).ObjectiveThese evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19 who do not have confirmed or suspected VTE.MethodsASH formed a multidisciplinary guideline panel, including 3 patient representatives, and applied strategies to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including performing systematic evidence reviews (up to March 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the grading of recommendations assessment, development, and evaluation (GRADE) approach to assess evidence and make recommendations, which were subject to public comment.ResultsThe panel agreed on 1 additional recommendation. The panel issued a conditional recommendation against the use of outpatient anticoagulant prophylaxis in patients with COVID-19 who are discharged from the hospital and who do not have suspected or confirmed VTE or another indication for anticoagulation.ConclusionsThis recommendation was based on very low certainty in the evidence, underscoring the need for high-quality randomized controlled trials assessing the role of postdischarge thromboprophylaxis. Other key research priorities include better evidence on assessing risk of thrombosis and bleeding outcomes in patients with COVID-19 after hospital discharge.

Background: COVID-19–related critical illness is associated with an increased risk of venous thromboembolism (VTE). Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19–related critical illness who do not have confirmed or suspected VTE. Methods: ASH formed a multidisciplinary guideline panel that included 3 patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process by performing systematic evidence reviews (up to 5 March 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the GRADE approach to assess evidence and make recommendations, which were subject to public comment. This is an update on guidelines published in February 2021. Results: The panel agreed on 1 additional recommendation. The panel issued a conditional recommendation in favor of prophylactic-intensity over intermediate-intensity anticoagulation in patients with COVID-19–related critical illness who do not have confirmed or suspected VTE. Conclusions: This recommendation was based on low certainty in the evidence, which underscores the need for additional high-quality, randomized, controlled trials comparing different intensities of anticoagulation in critically ill patients. Other key research priorities include better evidence regarding predictors of thrombosis and bleeding risk in critically ill patients with COVID-19 and the impact of nonanticoagulant therapies (eg, antiviral agents, corticosteroids) on thrombotic risk.

Bleeding is the main complication of oral anticoagulant (OAC) therapy, with major bleeds occurring in about 2% to 4% of OAC-treated patients per year. Although direct oral anticoagulants (DOACs) reduce the risk of major, fatal, and intracranial hemorrhage, major DOAC-related bleeding is associated with substantial morbidity and mortality, with case-fatality rates of 8% to 15% reported. Specific reversal agents for dabigatran (idarucizumab) and factor Xa inhibitors (andexanet) correct laboratory indices of anticoagulant effect. Clinical studies suggest that the majority of patients receiving these agents for DOAC-associated major bleeds experience clinical hemostasis. However, uncertainty remains regarding the incremental benefit of these agents and prothrombin complex concentrates over supportive measures alone, based on cohort studies that lacked control groups. Similar methodologic limitations preclude firm conclusions regarding the harms associated with use of these agents. Importantly, patients with DOAC-related major bleeding have substantial short-term risks of thrombosis and mortality, emphasizing the need for individualized patient assessment and protocolized bleed management strategies that include assessment of candidacy for safe resumption of OACs. With expanding indications and increasing prevalence of DOAC-eligible patients, bleeding complications and their management represent an ever-greater major health problem.

A 77-year-old man with atrial fibrillation and a CHA2DS2Vasc score of 6 for hypertension, age, diabetes, and previous stroke is brought to the emergency department with decreased level of consciousness. He is anticoagulated with rivaroxaban (a direct oral factor Xa inhibitor [FXaI]) and received his last dose about 4 hours before presentation. Urgent computed tomography of the head shows intracerebral hemorrhage. Because of his previous stroke, the patient’s family is concerned about treating the bleed with pharmacological agents that may increase the risk of stroke. What are the risks of thrombosis and mortality related to the use of prothrombin complex concentrates (PCCs) and andexanet alfa for patients with direct oral FXaI-associated major bleeding?

Direct oral anticoagulants are associated with lower rates of bleeding than vitamin K antagonists, but life-threatening bleeding still occurs. Andexanet alfa is a catalytically inactive recombinant modified human factor Xa molecule that reverses the anticoagulant effect of direct and indirect acting factor Xa inhibitors. In the ANNEXA-4 study, treatment with andexanet was associated with a 92% reduction in median anti-Xa activity levels and excellent or good hemostasis in 82% of patients presenting with serious bleeding while receiving apixaban or rivaroxaban. In this review, we discuss the burden of bleeding in anticoagulated patients and the need for reversal agents, review the mechanism of action of andexanet and critically evaluate the evidence for its efficacy and safety.

Patients with cirrhosis are not only at an increased risk of bleeding but also at risk of venous thromboembolism (VTE). We sought to determine the clinical characteristics, management, and outcomes after VTE in patients with cirrhosis. We used the data from RIETE (Registro Informatizado de la Enfermedad TromboEmbolica), an international registry of patients with VTE, to compare the outcomes in patients with and without cirrhosis. Main outcomes included all-cause mortality, pulmonary embolism (PE)-related mortality, recurrent VTE, and bleeding. Among 43,611 patients with acute VTE, 187 (0.4%) had cirrhosis. Of these, 184 (98.4%) received anticoagulation for a median of 109 days (interquartile range [IQR]: 43–201 days), most commonly with enoxaparin (median dose: 1.77 [IQR: 1.38–2.00] mg/kg/day). Compared with patients without cirrhosis, those with cirrhosis had a higher rate of all-cause mortality (10.7 vs. 3.4%; odds ratio [OR]: 3.41; 95% confidence interval [CI]: 2.03–5.46) and fatal bleeding (2.1 vs. 0.2%; OR: 13.94; 95% CI: 3.65–37.90) but similar rates of fatal PE (0.5 vs. 0.5%; OR: 1.17; 95% CI: 0.03–6.70). Patients with cirrhosis had a higher rate of all-cause mortality per 100 patient-years of follow-up (58.9 vs. 16.0; hazard ratio [HR]: 3.70; 95% CI: 2.69–4.91). One-year hazard ratio of clinically relevant bleeding (HR: 2.86; 95% CI: 1.91–4.27), fatal bleeding (HR: 8.51; 95% CI: 3.5–20.7), or recurrent VTE (HR: 2.08; 95% CI: 1.00–4.36) was higher in patients with cirrhosis. Cirrhosis is a challenging comorbidity in patients with VTE. Most patients were treated with anticoagulation and had an elevated risk of recurrence, similar risk of fatal PE, and a very high risk of bleeding including fatal bleeds.

BACKGROUND Right ventricular (RV) dysfunction predicts worse outcomes in acute pulmonary embolism (PE). Because computed tomography (CT) pulmonary angiography visualizes cardiac structures, it is a potential method for assessing RV function without the delays associated with inpatient echocardiography. OBJECTIVES We conducted a systematic review and meta-analysis to assess the diagnostic accuracy of CT scan findings for detecting RV dysfunction compared with echocardiography. METHODS We searched MEDLINE and EMBASE from inception to April 2020 for studies comparing RV dysfunction on CT scan with echocardiography standard. Study quality was assessed with the QUADAS-2 risk of bias tool. Meta-analysis was performed using a bivariate mixed effects regression framework. RESULTS After screening, 26 studies (3508 patients) were included. In a pooled analysis, septal deviation (5 studies; 459 patients) had a sensitivity of 0.31 (95% CI 0.25-0.38; I2 = 0%), specificity of 0.98 (95% CI 0.90-1.00; I2 = 59.4%), and positive likelihood ratio of 13.6 (95% CI 3.1-60.4) for RV dysfunction compared with echocardiography. The pooled sensitivity of increased RV/left ventricular ratio (21 studies; 3111 patients) was 0.83 (95% CI 0.78-0.87; I2 = 81.8%), whereas the pooled specificity was 0.75 (95% CI 0.66-0.82; I2 = 94.2%) and negative likelihood ratio was 0.23 (0.18-0.29). CONCLUSIONS Overall, RV dysfunction can be detected by CT imaging but the diagnostic accuracy when compared with echocardiography varies depending on specific findings. The presence of septal bowing appears to be highly specific for RV dysfunction. Our findings suggest that multiple CT findings of RV dysfunction may improve diagnostic accuracy and further studies are warranted.

Introduction There is an increased risk of stroke in patients with cancer–this risk is particularly heightened around the time of cancer diagnosis, although no studies have systematically quantified this risk in the literature. Patients newly diagnosed with cancer without prior stroke represent a highly susceptible population in whom there is a window of opportunity to study and implement primary prevention strategies. Therefore, the objective of this systematic review and meta-analysis is to identify the cumulative incidence of ischemic and hemorrhagic strokes during the first year after a diagnosis of cancer. Methods and analysis MEDLINE, EMBASE, and PubMed will be searched with the assistance from a medical information specialist, from 1980 until present. Eligible studies will include observational studies that have enrolled adult patients newly diagnosed with cancer and report outcomes of stroke during the first year of cancer diagnosis. We will exclude all randomized and non-randomized interventional studies. Data on participant characteristics, study design, baseline characteristics, and outcome characteristics will be extracted. Study quality will be assessed using the Newcastle-Ottawa Scale for cohort studies, and heterogeneity will be assessed using the I2 statistic. Pooled cumulative incidence will be calculated for ischemic and hemorrhagic strokes separately using a random-effects model. Ethics and dissemination No formal research ethics approval is necessary as primary data collection will not be done. We will disseminate our findings through scientific conference presentations, peer-reviewed publications, and social media/the press. The findings from this review will inform clinicians and patients regarding the risk of stroke in patients newly diagnosed with cancer by quantifying the cumulative incidence of each subtype of stroke during the first year after a diagnosis of cancer. This represents a window of opportunity to implement prevention strategies in a susceptible population. Registration ID with Open Science Framework osf.io/ucwy9.

Background Lack of data on balancing bleeding and thrombosis risk causes uncertainty about restarting anticoagulants after major bleeding. Anticoagulant reversal trials offer prospectively gathered data after major bleeding with well-documented safety events and restarting behavior. Objectives To examine the relationship of restarting anticoagulation with thrombosis, rebleeding, and death. Methods This is a posthoc analysis of a prospective factor Xa inhibitor reversal study at 63 centers in North America and Europe. We compared outcomes of restarted patients with those not restarted using landmark and time-dependent Cox proportional hazards models. Outcomes included thrombotic and bleeding events and death and a composite of all three. Results Of 352 patients enrolled, oral anticoagulation was restarted in 100 (28%) during 30-day follow-up. Thirty-four (9.7%) had thrombotic events, 15 (4.3%) had bleeding events (after day 3), and 49 (14%) died. In the landmark analysis comparing patients restarted within 14 days to those not, restarting was associated with decreased thrombotic events (hazard ratio [HR] = 0.112; 95% confidence interval [CI]: 0.001–0.944; p = 0.043) and increased rebleeding (HR = 8.39; 95% CI: 1.13–62.29; p = 0.037). The time-dependent Cox model showed evidence for a reduction in a composite (thrombotic events, bleeding, and death) attempting to capture net benefit (HR = 0.384; 95% CI: 0.161–0.915; p = 0.031). Conclusion This analysis provides modest evidence that restarting anticoagulation in factor Xa inhibitor-associated major bleeding patients is correlated with reduced risk of thrombotic events and increased risk of rebleeding. There is low-level evidence of net benefit for restarting. A randomized trial of restarting would be appropriate.

Background: Coronavirus disease 2019 (COVID-19)–related critical illness and acute illness are associated with a risk of venous thromboembolism (VTE). Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis for patients with COVID-19–related critical illness and acute illness who do not have confirmed or suspected VTE. Methods: ASH formed a multidisciplinary guideline panel and applied strict management strategies to minimize potential bias from conflicts of interest. The panel included 3 patient representatives. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic evidence reviews (up to 19 August 2020). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on 2 recommendations. The panel issued conditional recommendations in favor of prophylactic-intensity anticoagulation over intermediate-intensity or therapeutic-intensity anticoagulation for patients with COVID-19–related critical illness or acute illness who do not have confirmed or suspected VTE. Conclusions: These recommendations were based on very low certainty in the evidence, underscoring the need for high-quality, randomized controlled trials comparing different intensities of anticoagulation. They will be updated using a living recommendation approach as new evidence becomes available., Visual Abstract

Essentials The factors influencing anticoagulation management after gastrointestinal bleeding are unclear. Focus groups and a discrete choice experiments survey of health-care providers were conducted. Re-bleeding risk and thrombosis risk were the most important factors influencing decision making. Preference variability exists with a minority most sensitive to the anticoagulation indication. ABSTRACT: Background Oral anticoagulants (OACs) are permanently discontinued in up to 50% of patients after gastrointestinal (GI) bleeding despite evidence of benefit to restarting. Objectives We aimed to identify factors influencing health-care provider decision making regarding resuming OAC after GI bleeding and to identify preference groups. Patients/Methods We conducted focus group discussions (FGDs) with health-care providers. Themes identified and ranked through a dot voting exercise became the attributes for a discrete choice experiment survey of health-care providers developed using Sawtooth (Sawtooth Software, Provo, UT, USA). Hierarchical Bayes analysis was used to estimate preference coefficients (utilities) for each attribute. Preference groups were identified using latent class analysis. Results We conducted four FGDs involving 29 participants. The five most important factors identified in the FGDs were included in the survey. There were 250 survey respondents (mean age 45 years, 53% male). The most important factor was re-bleeding risk followed by thrombosis risk, index bleed severity, indication for OAC, and patient characteristics. Two preference groups were identified, a majority group (87% of respondents) placed the highest utility on re-bleeding risk followed by thrombosis risk, while a minority group (13% of respondents) placed the highest utility on OAC indication. Conclusions Overall, the most important factor influencing provider decision making was re-bleeding risk followed closely by thrombosis risk, although the indication for OAC was most important for a minority of respondents. This highlights variability among providers in an area lacking high-quality data to guide practice. Further research is needed to determine absolute rates of outcomes and patient values and preferences.

Despite decades of improvement in its diagnosis and management, venous thromboembolism (VTE) remains a significant cause of cardiovascular morbidity and mortality. Clinically relevant differences exist in the risk of symptomatic VTE among ethnoracial groups. Underlying these differences in rates of VTE are patterns of known genetic thrombophilias, which may also influence the risks of major bleeding related to vitamin K antagonists or direct oral anticoagulants. In addition, social factors, differential access to care, and disease awareness differ between ethnoracial groups, which contributes to disparities in VTE outcomes that include higher fatal events. The vast majority of participants included in clinical trials for the prevention and treatment of VTE have been White Caucasian, which limits our understanding of the differential impact of these agents in non-White ethnoracial groups. Increasing the participation in clinical trials of diverse ethnoracial groups should be a priority, especially those groups who are disproportionately affected by the burden of VTE, or possible bleeding complications when exposed to anticoagulants. Advocacy by patients, researchers, and regulatory bodies is crucial to ensure adequate enrolment of diverse ethnoracial groups in order to best inform clinical decisions to optimize VTE prevention and treatment for non-White populations.

ObjectiveTo investigate reasons for and impact of oral anticoagulation (OAC) in patients with atrial fibrillation (AF) at very low thromboembolic risk.MethodsIndividuals with CHA2DS2-VASc score 0 (men) or 1 (women) from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) were studied. Baseline characteristics according to OAC use were evaluated by logistic regression analysis. Non-haemorrhagic stroke or systemic embolism, major bleeding, cardiovascular and all-cause mortality were compared.ResultsFrom 2224 low CHA2DS2-VASc patients in GARFIELD-AF, 44% received OAC. In an adjusted model, increasing age up to 65 years (OR (95% CI)=1.31 (1.19 to 1.44)) and persistent AF (OR (95% CI)=3.25 (2.44 to 4.34)) or permanent AF (OR (95% CI)=2.29 (1.59 to 3.30)) versus paroxysmal/unclassified AF were associated with OAC use. Concomitant antiplatelet therapy (OR (95% CI)=0.21 (0.17 to 0.27)) was inversely associated. Crude incidence rates per 100 person-years over 2 years in patients on OAC versus not on OAC were 0.32 (95% CI 0.14 to 0.71) vs 0.30 (95% CI 0.14 to 0.63) for non-haemorrhagic stroke or systemic embolism, 0.21 (95% CI 0.08 to 0.57) vs 0.17 (95% CI 0.06 to 0.46) for major bleeding, 0.26 (95% CI 0.11 to 0.64) vs 0.26 (95% CI 0.12 to 0.57) for cardiovascular mortality and 0.74 (95% CI 0.44 to 1.25) vs 0.99 (95% CI 0.66 to 1.49) for all-cause mortality.ConclusionsIn contrast to guideline recommendations, almost half of real-world patients with AF at a very low thromboembolic risk according to the CHA2DS2-VASc score receive OAC. Persistent or permanent AF and increasing age up to 65 years are associated with OAC use, while concomitant antiplatelet therapy shows an inverse association. Regardless whether patients received OAC therapy, few thromboembolic and bleeding events occur, highlighting the low risk of this population.

Essentials The optimal dose and duration of thromboprophylaxis after bariatric surgery are unclear. We evaluated the safety of weight-adjusted tinzaparin prophylaxis in 1212 patients. In-hospital rates of venous thromboembolism and major bleeding were 0.2% and 1.8% respectively. In a sub-set of patients, trough anti-Xa levels did not show excessive anticoagulant activity. Summary Background Patients undergoing bariatric surgery are at moderate to high risk of venous thromboembolism (VTE). The optimal dose and duration of anticoagulant prophylaxis is uncertain. Objective To evaluate the safety of extended-duration weight-adjusted tinzaparin after bariatric surgery. Patients/methods We conducted a single-center retrospective cohort study of consecutive patients undergoing bariatric surgery who received weight-adjusted tinzaparin 4500-14 000 IU daily (75 IU kg-1 rounded to the nearest prefilled syringe) for 10 days after surgery (7-9 days post-hospital discharge). Primary safety outcomes were the frequency of VTE and major bleeding within 30 days of surgery in patients receiving at least one dose of tinzaparin. Results A total of 1279 patients undergoing bariatric surgery between July 2009 and December 2012 were reviewed, of whom 1212 received weight-adjusted tinzaparin. Safety outcomes were collected for 819 patients at 30 days, and for 1212 patients in-hospital only. The median age was 45.0 years, median weight was 130.0 kg and 98.8% of patients underwent gastric bypass or sleeve gastrectomy. In patients completing 30 days of follow-up, VTE occurred in 4/819 (0.5%) and major bleeding occurred in 13/819 patients (1.6%). In-hospital rates of VTE and major bleeding during surgical admission were 3/1212 (0.2%) and 22/1212 (1.8%), respectively. Conclusions Extended thromboprophylaxis with weight-adjusted tinzaparin appears to be a safe strategy after bariatric surgery, with low rates of postoperative VTE and major bleeding.

Essentials There remains clinical concern regarding the optimal management of direct oral (DOAC) anticoagulant effect for emergencies such as bleeding or urgent surgery/procedures.Idarucizumab is the preferred agent for urgent reversal of dabigatran for severe bleeding or urgent surgeries/procedures.There are currently no commercially available specific reversal agents for direct Xa inhibitors.Evidence for prothrombin complex concentrate (PCC), activated PCC (aPCC), and recombinant VIIa (rVIIa) is limited primarily to animal bleeding models and studies in human volunteer subjects.PCC, aPCC, or rVIIa may contribute to hemostasis for severe bleeding or urgent surgery/procedures in patients receiving factor Xa inhibitors, or dabigatran if idarucizumab is unavailable but benefits and harms are uncertain. The direct oral anticoagulants (DOACs) are used for stroke prevention in atrial fibrillation (SPAF) and the prevention and treatment of venous thromboembolic disease (VTE). Although DOAC‐associated bleeding events are less frequent as compared to vitamin K antagonists, there is significant concern surrounding physicians’ ability to evaluate and manage DOAC‐associated bleeding when it does occur. Idarucizumab is a specific reversal agent for dabigatran and is the agent of choice for dabigatran reversal in the setting of major bleeding or urgent surgery/procedures. There are no commercially available specific reversal agents for the direct Xa inhibitors. Although they have not been rigorously studied in DOAC‐treated patients requiring urgent anticoagulant reversal, limited evidence from in vitro studies, animal bleeding models, human volunteer studies (in vivo and in vitro) and case series suggest that coagulation factor replacement with prothrombin complex concentrate (PCC) and activated PCC (FEIBA) may contribute to hemostasis. However, the safety and efficacy of these agents and the optimal dosing strategies remain uncertain.

Cancer is a risk factor for thrombosis, but unlike venous thrombosis, its association with ischemic stroke, and its impact on stroke management and post-stroke outcomes are not well characterized. The primary objective of this study was to measure and compare the risk of ischemic stroke in individuals with a new diagnosis of cancer and those without a history of cancer in two separate matched cohorts based on the absence (Matched Cohort 1) or presence (Matched Cohort 2) of a prior diagnosis of ischemic stroke (Figure 1). Methods: We conducted a population-based matched cohort study of adults ≥18 years using linked clinical and administrative health databases in Ontario, Canada (2010 to 2019). Individuals with a new diagnosis of cancer were matched (1:1) to cancer-free controls by age and sex. Cancer diagnoses were determined using ICD-O-3 diagnostic codes (basal and squamous cell carcinoma and primary central nervous system tumors were excluded). For cancer patients, the index date was the diagnosis date and a corresponding dummy index date was assigned to the matched cancer-free control. The primary outcome was the incidence of ischemic stroke (time to ischemic stroke following index) determined using validated ICD-9 or -10 diagnostic codes from hospitalizations or emergency department visits. Analyses were conducted separately, in parallel, for each cohort. Standardized differences were used to compare the distributions of baseline characteristics. Cumulative incidence function (CIF) curves were generated for ischemic stroke and all-cause mortality. Competing risk methods were used to calculate sub-distribution adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for ischemic stroke, where death was treated as a competing event. Interactions with the timeline at 1.5 years after index were incorporated to assess if the hazard ratio for the main exposure (cancer vs cancer-free) varied before and after the 1.5-year mark. Regression analyses were adjusted using baseline characteristics for which there was imbalance between groups. Results: Matched Cohort 1 included 620,647 individuals with cancer and 620,647 controls. Matched Cohort 2 included 13,924 individuals with cancer and 13,924 controls. Baseline characteristics were generally well balanced (Table 1). Use of antithrombotic medications (prior to index) among individuals ≥66 years was similar between the groups (data not shown). CIF curves for ischemic stroke and mortality are shown in Figure 2. In Matched Cohort 1 (no history of stroke), the risk of ischemic stroke was increased in cancer patients compared to cancer-free controls 1.5 years post-index (aHR 1.40, 95%CI 1.34-1.47). From 1.5 years to 5 years, the risk of ischemic stroke was lower in cancer patients compared to controls (aHR 0.72, 95%CI 0.69-0.74). In Matched Cohort 2 (prior history of ischemic stroke), the risk of ischemic stroke was similar at 1.5 years after the index date in individuals with and without cancer (aHR 1.00, 95%CI 0.88-1.14). From 1.5 to 5 years, the risk of ischemic stroke was reduced (aHR 0.53, 95%CI 0.46-0.62) in cancer patients compared to controls. Conclusions: Compared to cancer-free controls, the risk of ischemic stroke among individuals with a new cancer diagnosis depended on the presence or absence of prior history of ischemic stroke, a novel finding not previously reported. In individuals without a prior history of stroke, those with cancer had a 1.5-fold higher risk of ischemic stroke at 1.5 years compared to controls. In individuals with a prior history of stroke, those with cancer had a similar risk of stroke compared to controls. At 5 years post-index, the risk of ischemic stroke was lower in cancer patients in both cohorts which may reflect high early mortality rates and lower stroke risk among long-term survivors of cancer. The risk of death among cancer patients was highest during the first 1.5 years after the index date in both cohorts. However, the magnitude of the risk increase was higher in individuals without a prior history of stroke (10-fold) compared to those with a prior history of cancer (5-fold). Limitations include unknown causes of death and unavailability of some covariates (e.g. smoking and antithrombotic use in individuals aged Figure 1 Figure 1. Disclosures Siegal: BMS-Pfizer: Honoraria; Leo Pharma: Honoraria; Novartis: Honoraria; Portola: Honoraria; Servier: Honoraria. Carrier: Pfizer: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Servier: Honoraria; Leo Pharma: Honoraria, Research Funding; Bayer: Honoraria; Sanofi: Honoraria. Gross: Valeo: Honoraria; Leo Pharma: Honoraria; Bayer: Honoraria; BMS-Pfizer: Honoraria.

James L. Januzzi, Jr, MD, FACC, Chair Luis C. Afonso, MBBS, FACC Brendan Everett, MD, FACC Adrian F. Hernandez, MD, FACC William Hucker, MD, PhD Hani Jneid, MD, FACC Dharam J. Kumbhani, MD, SM, FACC Joseph E. Marine, MD, FACC Pamela Bowe Morris, MD, FACC Robert Piana, MD, FACC Karol E.

Background: Right ventricular (RV) dysfunction is associated with higher mortality in patients with acute pulmonary embolism (PE). While precise definitions of RV dysfunction vary, up to 40% of patients with acute PE have evidence of RV dysfunction on echocardiography. The incremental utility of echocardiography for identifying RV dysfunction in acute PE is uncertain particularly when evidence of RV dysfunction is present on computed tomography (CT) pulmonary angiogram. However, the diagnostic utility of CT for detecting RV dysfunction is not well established; if CT is shown to have good diagnostic utility, it may reduce the need for routine urgent echocardiography and associated healthcare costs and resource use. We conducted a systematic review and meta-analysis to assess the diagnostic utility of CT scan findings for detecting RV dysfunction compared to echocardiography. Methods: Using a pre-specified protocol (Prospero ID: CRD42020187812) we systematically searched the MEDLINE and EMBASE databases from inception to April 2020. Studies of any design were included so long as they (i) included patients with acute PE diagnosed by CT scan and received an echocardiographic study within a reasonable timeframe and (ii) reported on test characteristics such that a 2x2 table could be constructed to compare the two diagnostic modalities with echocardiography considered the reference standard. Results were analyzed with the bivariate mixed-effects regression framework. Study quality was assessed with the QUADAS-2 risk of bias tool. Results: A total of 631 unique studies were identified by the search. After screening titles and abstracts and reviewing full texts in duplicate, 26 studies (n=3,404 patients) were eligible for inclusion. In individual studies, the average age (mean or median) of patients ranged from 41 to 70 years and 20% to 64.3% were female. The prevalence of RV dysfunction on echocardiography ranged studies from 22.6% to 85.7% and was 63.7% overall. The most common measurements on CT scan were increased RV/LV ratio (21 studies), pulmonary artery measurements (6 studies), RV dilatation or increased size (5 studies), measurements of vena cava size (3 studies), and coronary sinus size (2 studies). Other parameters included reflux of contrast into the inferior vena cava (IVC reflux, 4 studies) and interventricular septal deviation (5 studies). Different combinations of measurements were evaluated in 5 studies. Pooled analysis was performed for septal deviation, IVC reflux, and RV/LV ratio. In pooled analysis septal deviation had a sensitivity of 0.31 (95% CI=0.25- 0.38; I2= 51.6%) and a specificity of 0.98 (95% CI=0.90 - 1.00; I2= 46.9%). IVC reflux had a sensitivity of 0.75 (95% CI = 0.40 - 0.93; I2=95.9%) and specificity 0.75 (95% CI=0.47 - 0.93; I2= 91.1%). Where multiple RV/LV ratios were reported, we utilized the one with the highest sensitivity. The pooled sensitivity of increased RV/LV ratio was 0.83 (95% CI=0.78 - 0.87; I2= 82.9) while the pooled specificity was 0.75 (95% CI=0.66- 0.82; I2= 94.6) (Figure 1). Considering all RV/LV ratio studies, the summary receiver operating characteristic (SROC) curve had an area under the curve (AUC) of 0.86 (0.83-0.89) for identifying the presence of RV dysfunction present on echocardiography. Overall, most studies were considered at high risk of bias. Subgroup analyses demonstrated that sensitivity was significantly affected by the risk of bias for RV/LV ratio for all QUADAS-2 domains. Specificity was not affected by the risk of bias for any of the QUADAS-2 domains. Conclusions: Our results suggest CT imaging findings appear to have moderate to good diagnostic utility for detecting the presence of RV dysfunction in acute PE. With the exception of septal deviation there was significant heterogeneity amount included studies. Overall, increased RV/LV ratio had the best test characteristics (sensitivity 0.83, specificity 0.75 and AUC 0.86). However, the veracity of these findings is limited by the high risk of bias among included studies. Further analyses regarding the diagnostic utility of combinations of multiple CT findings are warranted. Figure 1 Disclosures Crowther: Pfizer: Speakers Bureau; Alnylam: Divested equity in a private or publicly-traded company in the past 24 months; CSL Behring: Speakers Bureau; Servier Canada: Membership on an entity's Board of Directors or advisory committees; Diagnostica Stago: Speakers Bureau; Asahi Kasei: Membership on an entity's Board of Directors or advisory committees; Precision Biologicals: Membership on an entity's Board of Directors or advisory committees; Hemostais Reference Laboratories: Honoraria. Siegal:BMS Pfizer: Honoraria; Bayer: Honoraria; Novartis: Honoraria; Leo Pharma: Honoraria; Portola: Honoraria.

Background: Contemporary treatment of Myeloproliferative Neoplasms (MPNs) has altered their natural history. Frailty, a state of reduced physiologic reserve is prevalent among older individuals, and increases risk for cardiovascular disease (CVD) and other adverse health outcomes. However, little is known about frailty in MPNs. An improved characterization of frailty may inform MPN treatment goals including the impact of treatment on frailty and CVD. Methods : We utilized the ORCHID database, a multi-centre prospective observational registry of MPN patients. Frailty-related factors collected included: unintentional weight loss (>4kg lost in prior year); grip strength (below 20th percentile for age and sex); Timed Up and Go test (TGUG) greater than 13.5 seconds (indicative of high fall risk); self-reported exhaustion; and cognitive frailty measured by the Digit Symbol Substitution test (DSST). Baseline information on cardiovascular event history was also collected. Results: In total, 150 patients were included (56 CML, 28 ET, 14 PMF, 52 PV). Baseline information and past medical history are detailed in Table 1. Cardiovascular events prior to diagnosis were most common in patients with PV (7.7% MI and 5.8% stroke). Past medical history of Venous Thromboembolism (VTE) was more common in Ph-negative MPNs (15.3% PV, 21.4% PMF, 21.4% ET) compared to CML where VTE history was absent. Hypertension and dyslipidaemia were overall the most common cardiovascular comorbidities. The burden of depression was highest in PMF with 30.7% of patients reporting a PHQ-9 score ≥ 10. Frailty related outcomes are detailed in Table 2. All four MPNs had high rates of frailty in every domain at baseline. Among Ph- MPNs (ET, PV, and PMF), ET and PV patients generally had a lower burden of frailty compared to PMF patients in most measurements. A high risk of falls as determined by a prolonged get-up-and-go test was present in approximately 20% of PV, CML, and ET patients and 42% of PMF patients. ET patients had the lowest self-reported exhaustion, with less than 40% reporting they ever felt "everything was an effort" or that they "just couldn't get going". PMF patients had the highest self-reported exhaustion. The proportion of patients with low DSST scores was greater in PMF (38.5%) and PV patients (24.3%) than ET (20%) and CML (15%) patients. Unintentional weight loss was common across MPN patients (33.9% to 50%). Conclusion: There is a high rate of baseline frailty among patients with MPNs with domains differing between diseases. In this cohort, cardiovascular event history at diagnosis was highest among PV patients and lowest in CML patients. Disclosures Siegal: Leo Pharma: Honoraria; Novartis: Honoraria; Portola: Honoraria; Bayer: Honoraria; BMS Pfizer: Honoraria. Hillis:Roche: Honoraria.

OBJECTIVES The benefits of preoperative intravenous (IV) iron treatment in cardiac surgery patients with preoperative anaemia or iron deficiency have not been well-established. We performed a systematic review and meta-analysis to determine the effects of treating preoperative anaemia or iron deficiency with IV iron in adult cardiac surgery patients. METHODS We searched Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval Systems Online and Excerpta Medica Database for randomized controlled trials (RCTs) and observational studies comparing IV iron to oral iron or no iron. We performed title and abstract, full-text screening, data extraction and risk of bias assessment independently and in duplicate. We pooled data using a random effects model and evaluated the overall quality of evidence. RESULTS We identified 4 RCTs and 7 observational studies. Pooled data from observational studies suggested a benefit of IV iron compared to no iron on mortality [relative risk 0.39, 95% confidence interval (CI) 0.23–0.65; P CONCLUSIONS This meta-analysis suggests that IV iron improves postoperative morbidity in adult cardiac surgery patients with preoperative anaemia or iron deficiency. A large, rigorous, placebo-controlled, double-blinded, multicentre trial is needed to clarify the role of IV iron in this patient population. Clinical trial registration International prospective register of systematic reviews ID Number CRD42019122844

Background Oral anticoagulants (OAC) are permanently discontinued in up to 50% of patients after gastrointestinal (GI) bleeding despite ongoing thrombotic risk and evidence of benefit to restarting. The reasons for permanent discontinuation of OAC are unclear, but likely include concerns about re-bleeding and a lack of high-quality evidence. There are no studies evaluating healthcare provider values and preferences following OAC-related GI bleeding and their influence on decision-making about whether and when to resume OACs. Aims We aimed to (i) identify key factors (attributes) that influence healthcare provider decision-making regarding resumption of OAC after GI bleeding, (ii) determine the relative importance of these attributes, and (iii) to identify preference groups. Methods We conducted focus group discussions (FGD) with healthcare providers involved in the care of patients with OAC-related GI bleeding. Participants ranked the relative importance of the attributes identified during the FGD through a dot voting exercise. Transcripts were reviewed and themes (attributes) were identified. Results of the FGD informed a discrete choice experiments survey developed and analyzed using the Sawtooth software platform (Sawtooth Software, USA). The survey was pilot tested and modified by iterative feedback. A sample choice task is shown in Image 1. Hierarchical Bayes analysis was used to estimate preference coefficients (utilities) for each attribute. Latent class analysis was used to identify preference groups. Results There were 4 FGD involving 29 participants. The most important attributes identified and included in the survey were thrombosis risk, indication for OAC, index bleed severity, re-bleeding risk, and patient characteristics. There were 130 survey respondents practicing in hematology (n=68), internal medicine (n=30), gastroenterology (n=7), cardiology (n=4), family medicine (n=3), and others (n=18). The mean age was 45 years (±11) and 51% were male. Thrombosis risk and re-bleeding risk equally had the highest utility followed by index bleed severity, patient characteristics, and indication for OAC. Two preference groups were identified. The dominant preference group (78% of respondents) placed the highest utility on thrombosis risk and re-bleeding risk, while a minority (22% of respondents) placed the highest utility on index bleed severity. Conclusions Thrombosis risk and re-bleeding risk are equally the most important factors influencing OAC resumption following OAC-related GI bleeding. The severity of the index bleed is the most important factor in decision-making for a minority segment of healthcare providers. Further research on the dose, type and timing of OAC resumption is needed to determine the optimal balance between thrombosis and re-bleeding. Funding Agencies Heart and Stroke Foundation

Summary Background In non-surgical settings, covert stroke is more common than overt stroke and is associated with cognitive decline. Although overt stroke occurs in less than 1% of adults after non-cardiac surgery and is associated with substantial morbidity, we know little about perioperative covert stroke. Therefore, our primary aim was to investigate the relationship between perioperative covert stroke (ie, an acute brain infarct detected on an MRI after non-cardiac surgery in a patient with no clinical stroke symptoms) and cognitive decline 1 year after surgery. Methods NeuroVISION was a prospective cohort study done in 12 academic centres in nine countries, in which we assessed patients aged 65 years or older who underwent inpatient, elective, non-cardiac surgery and had brain MRI after surgery. Two independent neuroradiology experts, masked to clinical data, assessed each MRI for acute brain infarction. Using multivariable regression, we explored the association between covert stroke and the primary outcome of cognitive decline, defined as a decrease of 2 points or more on the Montreal Cognitive Assessment from preoperative baseline to 1-year follow-up. Patients, health-care providers, and outcome adjudicators were masked to MRI results. Findings Between March 24, 2014, and July 21, 2017, of 1114 participants recruited to the study, 78 (7%; 95% CI 6–9) had a perioperative covert stroke. Among the patients who completed the 1-year follow-up, cognitive decline 1 year after surgery occurred in 29 (42%) of 69 participants who had a perioperative covert stroke and in 274 (29%) of 932 participants who did not have a perioperative covert stroke (adjusted odds ratio 1·98, 95% CI 1·22–3·20, absolute risk increase 13%; p=0·0055). Covert stroke was also associated with an increased risk of perioperative delirium (hazard ratio [HR] 2·24, 95% CI 1·06–4·73, absolute risk increase 6%; p=0·030) and overt stroke or transient ischaemic attack at 1-year follow-up (HR 4·13, 1·14–14·99, absolute risk increase 3%; p=0·019). Interpretation Perioperative covert stroke is associated with an increased risk of cognitive decline 1 year after non-cardiac surgery, and perioperative covert stroke occurred in one in 14 patients aged 65 years and older undergoing non-cardiac surgery. Research is needed to establish prevention and management strategies for perioperative covert stroke. Funding Canadian Institutes of Health Research; The Ontario Strategy for Patient Oriented Research support unit; The Ontario Ministry of Health and Long-Term Care; Health and Medical Research Fund, Government of the Hong Kong Special Administrative Region, China; and The Neurological Foundation of New Zealand.