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Many patients with impaired renal function have concurrent indications for anticoagulant therapy, including atrial fibrillation and venous thromboembolism. For mild chronic kidney disease, data from clinical trials and existing guidelines can be applied to clinical management. The benefits and harms of anticoagulation therapy in patients with more advanced renal impairment are nuanced, as both thrombotic and bleeding risk are increased. Until recently, data regarding anticoagulants in severe renal impairment were primarily observational, but emerging evidence includes a few small clinical trials and the emergence of novel agents hypothesized to have improved efficacy and safety in this population. In this review, we summarize existing data on anticoagulation in patients with chronic kidney disease. We suggest a framework for anticoagulation decision-making in the burgeoning worldwide population of patients with chronic kidney disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Venous thromboembolism (VTE) is the third leading cause of preventable hospital-associated (HA) death. Most HA-VTE, including fatal pulmonary emboli, occur among medically ill patients. The rate of symptomatic VTE more than doubles over the first 21 days after hospital discharge. Trials have demonstrated that the burden of HA-VTE may be reduced with postdischarge thromboprophylaxis; however, few patients receive this therapy. We formerly validated the ability of eVTE (eVTE is the abbreviation for a risk assessment tool constituted by 2 calculations: one predicts 90-day VTE and the other predicts 30-day major bleeding derived from only elements of the complete blood count and basic metabolic panel and age) to identify medical patients being discharged with both an elevated risk of VTE and a low risk of bleeding., Objectives: Implement a cluster-randomized, stepped wedge, type II hybrid implementation/effectiveness trial generating an alert among select at-risk patients upon discharge for implementation of thrombosis chemoprophylaxis in a 23-hospital not-for-profit healthcare system., Methods: We use the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework to guide implementation and outcomes reporting., Results: The primary outcome for aim 1 (implementation) is the prescription of rivaroxaban 10 mg daily for 30 days as postdischarge thromboprophylaxis among at-risk patients. The primary efficacy and safety outcomes (effectiveness) are the 90-day composite of symptomatic VTE, myocardial infartcion, nonhemorrhagic stroke, all-cause mortality, and 30-day major bleeding., Conclusion: The eVTE trial will provide high-quality, real-world evidence on the effectiveness and safety of a pragmatic intervention to implement targeted postdischarge thromboprophylaxis using decision support embedded in the electronic health record., (© 2024 The Author(s).)

The American College of Chest Physicians (CHEST) Antithrombotic Therapy for Venous Thromboembolism Disease evidence-based guidelines are now updated in a more frequent, focused manner. Guidance statements from the most recent full guidelines and two subsequent updates have not been gathered into a single source. An international panel of experts with experience in prior antithrombotic therapy guideline development reviewed the 2012 CHEST antithrombotic therapy guidelines and its two subsequent updates. All guideline statements and their associated patient, intervention, comparator, and outcome questions were assembled. A modified Delphi process was used to select statements considered relevant to current clinical care. The panel further endorsed minor phrasing changes to match the standard language for guidance statements using the modified Grading of Recommendations, Assessment, Development, and Evaluations (ie, GRADE) format endorsed by the CHEST Guidelines Oversight Committee. The panel appended comments after statements deemed as relevant, including suggesting that statements be updated in future guidelines because of interval evidence. We include 58 guidance statements from prior versions of the antithrombotic therapy guidelines, with updated phrasing as needed to adhere to contemporary nomenclature. Statements were classified as strong or weak recommendations based on high-certainty, moderate-certainty, and low-certainty evidence using GRADE methodology. The panel suggested that five statements are no longer relevant to current practice. As CHEST continues to update guidance statements relevant to antithrombotic therapy for VTE disease, this article serves as a unified collection of currenrtly relevant statements from the preceding three guidelines. Suggestions have been made to update specific statements in future publications., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: L. B. K. reports receiving research funding from CSL Behring and Takeda to her institution for unrelated research. None declared S. M. S., S. C. W., K. D., G.-J. G., F. A. K., C. S. K., S. M., J. R. E. V., P. S. W., S. W., and L. K. M., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The direct anticoagulants (DOACs), apixaban and rivaroxaban, are used for extended-phase treatment of venous thromboembolism (VTE) and have labeling for dose reduction for this indication. The objective of this study was to better understand primary care clinician prescribing patterns of apixaban and rivaroxaban for extended-phase anticoagulation. We conducted a 21-question survey targeting members of the American College of Physicians and United States Veterans Administration anticoagulation management services. Survey questions covered prescribing behaviors for dose reduction of apixaban and rivaroxaban for extended VTE treatment, as well as questions related to the respondent's practice setting. We used logistic regression to assess associations between demographics and prescribing behaviors. We used k-means clustering to identify distinct groups of prescribing patterns. Among 227 respondents, most were attending physicians (60%) and one-third (34%) practiced in internal medicine or primary care. Most (59%) indicated they dose-reduced DOACs. Hospitalists (no outpatient care) were least likely to dose-reduce (OR 0.09 [95% CI 0.03-0.22]), as well as early-career clinicians (0.53 [0.30-0.91]). Pharmacists and clinicians who treat over 500 VTE patients annually were most likely to dose reduce (6.4 [2.9-16.3]), (2.9 [1.5-6.0]), respectively. We identified five clusters of dosing behaviors and characterized clinician makeup. Clusters were primarily differentiated by frequency of dose reduction, DOAC preference, and temporary re-escalation of doses. We identified clinician characteristics that are associated with dose-reduction prescribing behaviors; these analyses provide insight into where targeted interventions, such as protocolization and education, would be most beneficial.

Introduction: Management of below-knee DVT (BKDVT) in trauma patients is uncertain. We hypothesized that BKDVT can be managed with observation only., Methods: Secondary analysis on trauma inpatients March 2017-September 2019 with risk assessment profile ≥5. Management of BKDVT included observation with ultrasound. BKDVT was compared to above-knee DVT (AKDVT), and BKDVT with progression to AKDVT/PE compared to no progression., Results: Of 1988 patients, 136 (6.8%) BKDVT and 23 (1.2%) AKDVT. 7 (6.9%) BKDVT progressed to AKDVT/PE. 6.9% had BKDVT progression, associated with higher ISS (36.7 vs 21.6, p ​= ​0.005), longer prophylaxis delay (121 vs 45 ​h, p ​= ​0.02) and longer hospital LOS (25.6 vs 7.8, p ​= ​0.01). None experienced post-thrombotic syndrome., Conclusion: Majority of BKDVT in hospitalized trauma patients did not progress to AKDVT. Observation for progression, rather than treatment, was not associated with increased PE risk or thrombotic sequelae. Observation with serial ultrasound may serve as a practical alternative to anticoagulation in trauma patients with BKDVT., Competing Interests: Declaration of competing interest None of the authors have anything to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: In patients with acute deep vein thrombosis (DVT) treated with catheter-based thrombolysis and venous stenting, poststenting anticoagulant management is uncertain., Objectives: To determine the type and duration of antithrombotic therapy used in patients who have received venous stents for treatment of acute lower extremity DVT., Methods: We created an international registry of patients with leg DVT from 2005 to 2019 who received venous stents as part of their acute management. We collected data on baseline clinical characteristics and pre-venous and post-venous stent antithrombotic therapy., Results: We studied 173 patients with venous stents: 101 (58%) were aged ≤50 years, 105 (61%) were female, and 128 (74%) had risk factors for thrombotic disease. DVT was iliofemoral in 150 (87%) patients, and catheter-based treatment was given within 7 days of diagnosis in 92 (53%) patients. After venous stenting, 109 (63%) patients received anticoagulant-only therapy with a direct oral anticoagulant (29%), warfarin (22%), or low-molecular-weight heparin (10%), and 59 (34%) received anticoagulant-antiplatelet therapy. In patients taking anticoagulant-only therapy, 29% received indefinite treatment; in patients on anticoagulant-antiplatelet therapy, 19% received indefinite treatment. Factors associated with combined anticoagulant-antiplatelet therapy vs anticoagulant-only therapy were use of thrombolytic, thrombectomy, and aspiration interventions (odds ratio [OR], 5.11; 95% CI, 1.45-18.05); use of balloon angioplasty (OR, 2.62; 95% CI, 1.20-5.76); and immediate stent restenosis (OR, 7.2; 95% CI, 1.45-5.89)., Conclusion: Anticoagulant therapy without concomitant antiplatelet therapy appears to be the most common antithrombotic strategy in patients with DVT and venous stenting. More research is needed to determine outcomes of venous stenting in relation to antithrombotic therapy., Competing Interests: Declaration of competing interests J.D.D. reports personal fees from Pfizer, Servier, Fresinius-Kabi, and Leo Pharma; and grants from Canadian Institutes of Health Research outside the submitted work. The remaining authors report no conflicts of interest., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Patient-reported outcome measures (PROMs) are patient-completed instruments that capture patient-perceived health status and well-being. PROMs measure disease impact and outcomes of care as reported by those who experience the disease. After pulmonary embolism or deep vein thrombosis, patients may face a broad spectrum of complications and long-term sequelae beyond the usual quality-of-care indicators of recurrent venous thromboembolism (VTE), bleeding complications, and survival. The full impact of VTE on individual patients can only be captured by assessing all relevant health outcomes from the patient's perspective in addition to the traditionally recognized complications. Defining and measuring all important outcomes will help facilitate treatment tailored to the needs and preferences of patients and may improve health outcomes. The International Society on Thrombosis and Haemostasis Scientific and Standardization Committee Subcommittee on Predictive and Diagnostic Variables in Thrombotic Disease endorsed the International Consortium for Health Outcomes Measurement (ICHOM) VTE project on development of a standardized set of patient-centered outcome measures for patients with VTE. In this communication, the course and result of the project are summarized, and based on these findings, we propose recommendations for the use of PROMs during clinical follow-up of patients with VTE. We describe challenges to implementation of PROMs and explore barriers and enablers., Competing Interests: Declaration of competing interests A.L.P. reports a grant from the National Institute on Aging (R03AG074074). S.C.W. reports funding for research from Bristol-Myers Squibb paid to his institution and support (expenses only) for attending Anticoagulation Forum, San Francisco, as an invited guest lecturer. F.A.K. reports grants or contracts from Bayer, BMS, BSCI, MSD, Leo Pharma, Actelion, VarmX, the Netherlands Organisation for Health Research and Development, the Dutch Thrombosis Association, the Dutch Heart Foundation, the Netherlands, and the Horizon Europe Program, all unrelated to this work and paid to his institution. C.M.M.d.J., K.d.W., S.A.B., A.M.G., C.M., H.R.-E., and R.T. have no competing interests to disclose., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Deep vein thrombosis (DVT) is common in pregnancy, yet data are limited on the best diagnostic strategies in pregnant patients suspected of DVT., Objectives: We conducted a prospective cohort study to evaluate the rate of symptomatic DVT in the 90 days after a negative whole-leg compression ultrasound (CUS) in pregnant women presenting with DVT symptoms., Methods: In this prospective cohort study, we enrolled pregnant patients suspected of DVT between 2011 and 2019 who were referred to the vascular imaging laboratory at a tertiary care center and had anticoagulation held after a negative whole-leg CUS. Primary outcome was objectively confirmed DVT or pulmonary embolism or death due to venous thromboembolism (VTE)., Results: Whole-leg CUS yielded normal results in 186 patients (97.9%) and identified DVT in 4 (2.1%). The mean age was 30 and 164 were White. Among the 186 patients with a negative, initial whole-leg CUS who did not receive anticoagulation, there were 2 DVT events identified over the 90-day follow-up period, for an overall rate of 1.1% (95% CI: 0.2-3.4%). The study was terminated before full planned accrual for administrative reasons., Conclusion: The rate of symptomatic DVT is low in pregnant patients who have a single, negative whole-leg CUS and did not receive anticoagulation. Adequately powered studies should prospectively assess whole-leg CUS in a larger population alone and in combination with pre-test probability scores and/or D-dimer to determine its role in the evaluation of suspected DVT in pregnancy., (© 2023 The Authors.)

Background: Post-hospitalization thromboprophylaxis can reduce venous thromboembolism (VTE) risk for non-surgical patients but may carry bleeding risks. We aimed to externally validate the Intermountain Risk Scores for hospital-associated venous thromboembolism (HA-VTE IMRS) and major bleeding (HA-MB IMRS) for VTE and bleeding outcomes., Methods: Retrospective cohort study of adult patients discharged alive from medical services between 2015 and 2019. HA-VTE IMRS and HA-MB IMRS were calculated at the time of hospital discharge and dichotomized as high- or low-risk as described in the derivation manuscript. 90-day post-discharge VTE outcomes were assessed from diagnostic radiology reports, and bleeding outcomes were assessed using ICD-10 codes and blood bank transfusion records., Results: Among 113,578 patients in the study, 66,340 patients (58.4 %) had a low-risk HA-VTE IMRS <7, versus 47,238 (41.6 %) high-risk ≥7. For bleed prediction, 71,576 patients (63 %) had a low-risk HA-MB IMRS <8, versus 42,002 (37 %) high-risk ≥8. VTE incidence was 1.1 % and 0.6 % while major bleeding incidence was 1.3 % and 0.1 % in high-risk versus low-risk cohorts, respectively. AUCs for VTE and bleed outcome discrimination were 0.59 and 0.78, respectively. Patients with a combined high-risk VTE score and low-risk bleeding score comprised 14.5 % of the population., Conclusion: In this external validation study, the HA-VTE IMRS had poor discrimination for VTE but the HA-MB IMRS had good discriminatory ability for major bleeding events. A sizable minority of patients were categorized as high VTE risk with low bleed risk, a population which may have an optimal risk-benefit profile for post-hospital thromboprophylaxis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GDB – consulting for Pfizer, Bristol-Myers Squibb, Janssen, Abbott Vascular, Boston Scientific, Bayer; grant funding from Boston Scientific; Board of Directors for Anticoagulation Forum. BDH – grant funding from AstraZeneca, the Intermountain Research and Medical Foundation, the Patient-Centered Outcomes Research Institute; scientific advisory boards for Opsis Health and Lab Me Analytics; intellectual property licensed by Intermountain to Alluceo and CareCentra., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Assessment for risks associated with acute stable COVID-19 is important to optimize clinical trial enrollment and target patients for scarce therapeutics. To assess whether healthcare system engagement location is an independent predictor of outcomes we performed a secondary analysis of the ACTIV-4B Outpatient Thrombosis Prevention trial., Methods: A secondary analysis of the ACTIV-4B trial that was conducted at 52 US sites between September 2020 and August 2021. Participants were enrolled through acute unscheduled episodic care (AUEC) enrollment location (emergency department, or urgent care clinic visit) compared to minimal contact (MC) enrollment (electronic contact from test center lists of positive patients).We report the primary composite outcome of cardiopulmonary hospitalizations, symptomatic venous thromboembolism, myocardial infarction, stroke, transient ischemic attack, systemic arterial thromboembolism, or death among stable outpatients stratified by enrollment setting, AUEC versus MC. A propensity score for AUEC enrollment was created, and Cox proportional hazards regression with inverse probability weighting (IPW) was used to compare the primary outcome by enrollment location., Results: Among the 657 ACTIV-4B patients randomized, 533 (81.1%) with known enrollment setting data were included in this analysis, 227 from AUEC settings and 306 from MC settings. In a multivariate logistic regression model, time from COVID test, age, Black race, Hispanic ethnicity, and body mass index were associated with AUEC enrollment. Irrespective of trial treatment allocation, patients enrolled at an AUEC setting were 10-times more likely to suffer from the adjudicated primary outcome, 7.9% vs. 0.7%; p < 0.001, compared with patients enrolled at a MC setting. Upon Cox regression analysis adjustment patients enrolled at an AUEC setting remained at significant risk of the primary composite outcome, HR 3.40 (95% CI 1.46, 7.94)., Conclusions: Patients with clinically stable COVID-19 presenting to an AUEC enrollment setting represent a population at increased risk of arterial and venous thrombosis complications, hospitalization for cardiopulmonary events, or death, when adjusted for other risk factors, compared with patients enrolled at a MC setting. Future outpatient therapeutic trials and clinical therapeutic delivery programs of clinically stable COVID-19 patients may focus on inclusion of higher-risk patient populations from AUEC engagement locations., Trial Registration: ClinicalTrials.gov Identifier: NCT04498273., (© 2023. The Author(s).)

The effectiveness and safety of direct oral anticoagulants (DOAC) compared with warfarin remains uncertain in obese patients. We assessed the comparative effectiveness and safety of DOACs with warfarin for the treatment of VTE among obese patients. This multi-center retrospective cohort study included adults with a BMI ≥ 35 kg/m 2 or weight ≥ 120 kg prescribed either DOAC (apixaban, dabigatran, edoxaban, rivaroxaban) or warfarin for a VTE diagnosis. The primary outcome was the 12-month rate of recurrent VTE. The secondary outcome was the 12-month rate of major bleeding. Among 5626 patients, 67% were prescribed warfarin and 33% were prescribed a DOAC. The 12-month VTE recurrence rate was 3.6% (67/1823) for patients treated with DOAC compared with 3.8% (143/3664) for patients treated with warfarin [odds ratio for recurrent VTE on warfarin versus DOAC (OR) (95% CI).07 (0.80, 1.45)]. The 12-month major bleeding rate was 0.5% (10/1868) for patients on DOAC versus 2.4% (89/3758) on warfarin [OR 4.25 (2.19, 8.22)]. Similar proportions of recurrent VTE occurred across BMI thresholds on DOAC and warfarin: for BMI ≥ 35 kg/m 2 (N = 5412), 3.6% versus 3.8%, respectively [OR 1.08 (0.80, 1.46)]; for BMI ≥ 40 kg/m 2 (N = 2321), 4.4% versus 3.5%, respectively [OR 0.80 (0.51, 1.26)]; and for BMI ≥ 50 kg/m 2 (N = 560), 3.1% versus 3.7%, respectively [OR 1.18 (0.39, 3.56)]. Similar proportions of recurrent VTE occurred in patients with obesity treated for VTE with DOACs and warfarin. DOACs were associated with lower major bleeding compared to warfarin in patients with obesity and VTE., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Venous thromboembolism (VTE) occurs in 0.4% to 15.5% and bleeding occurs in 20% to 35% of patients after liver transplantation (LT). Balancing the risk of bleeding from therapeutic anticoagulation and risk of thrombosis in the postoperative period is challenging. Little evidence exists regarding the best treatment strategy for these patients. We hypothesized that a subset of LT patients who develop postoperative deep vein thromboses (DVTs) could be managed without therapeutic anticoagulation. We implemented a quality improvement (QI) initiative using a standardized Doppler ultrasound-based VTE risk stratification algorithm to guide parsimonious implementation of therapeutic anticoagulation with heparin drip., Methods: In a prospective management QI initiative for DVT management, we compared 87 LT historical patients (control group; January 2016-December 2017) to 182 LT patients (study group; January 2018-March 2021). We analyzed the rates of immediate therapeutic anticoagulation after DVT diagnosis within 14 d of LT, clinically significant bleeding, return to the operating room, readmission, pulmonary embolism, and death within 30 d of LT before and after the QI initiative., Results: Ten patients (11.5%) in the control group and 23 patients (12.6%; P  = 0.9) in the study group developed DVTs after LT. Immediate therapeutic anticoagulation was used in 7 of 10 and 5 of 23 patients in the control and study groups, respectively ( P  = 0.024). The study group had lower odds of receiving immediate therapeutic anticoagulation after VTE (21.7% versus 70%; odds ratio = 0.12; 95% confidence interval, 0.019-0.587; P  = 0.013) and a lower rate of postoperative bleeding (8.7% versus 40%; odds ratio = 0.14, 95% confidence interval, 0.02-0.91; P  = 0.048). All other outcomes were similar., Conclusions: Implementing a risk-stratified VTE treatment algorithm for immediate post-LT patients appears to be safe and feasible. We observed a decrease in the use of therapeutic anticoagulation and a lower rate of postoperative bleeding without adverse impacts on early outcomes., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: The efficacy and safety of direct oral anticoagulants (DOACs) for patients with thrombotic antiphospholipid syndrome remain controversial., Objectives: The authors performed a systematic review and meta-analysis of randomized controlled trials that compared DOACs with vitamin K antagonists (VKAs)., Methods: We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials through April 9, 2022. The 2 main efficacy outcomes were a composite of arterial thrombotic events and venous thromboembolic events (VTEs). The main safety outcome was major bleeding. Random effects models with inverse variance were used., Results: Our search retrieved 253 studies. Four open-label randomized controlled trials involving 472 patients were included (mean control-arm time-in-therapeutic-range 60%). All had proper random sequence generation and adequate allocation concealment. Overall, the use of DOACs compared with VKAs was associated with increased odds of subsequent arterial thrombotic events (OR: 5.43; 95% CI: 1.87-15.75; P < 0.001, I 2  = 0%), especially stroke, and the composite of arterial thrombotic events or VTE (OR: 4.46; 95% CI: 1.12-17.84; P = 0.03, I 2  = 0%). The odds of subsequent VTE (OR: 1.20; 95% CI: 0.31-4.55; P = 0.79, I 2  = 0%), or major bleeding (OR: 1.02; 95% CI: 0.42-2.47; P = 0.97; I 2  = 0%) were not significantly different between the 2 groups. Most findings were consistent within subgroups., Conclusions: Patients with thrombotic antiphospholipid syndrome randomized to DOACs compared with VKAs appear to have increased risk for arterial thrombosis. No significant differences were observed between patients randomized to DOACs vs VKAs in the risk of subsequent VTE or major bleeding., Competing Interests: Funding Support and Author Disclosures Dr Piazza has received research support from Bristol Myers Squibb/Pfizer Alliance, Bayer, Janssen, Alexion, Amgen, and Boston Scientific Corporation; and has received consulting fees from Bristol Myers Squibb/Pfizer Alliance, Boston Scientific Corporation, Janssen, Namsa, Prairie Education and Research Cooperative, Boston Clinical Research Institute, and Amgen. Dr Jiménez has received research support from Daiichi-Sankyo and Sanofi; and has received consulting fees from Bristol Myers Squibb/Pfizer Alliance, Daiichi-Sankyo, Leo Pharma, Rovi, and Sanofi. Dr Monreal has received research support from Sanofi, Leo, and Rovi; and has received consulting fees from Sanofi. Dr Pengo has received lecture fees from Werfen Group. Dr Cortes-Hernandez has received institutional research funding from Bayer Hispania to conduct the APS RCT. Dr Connors has received research funding to her institution from CSL Behring; has received consulting fees from Abbott; has received honoraria for lectures from Bristol Myers Squibb, Roche, and Sanofi; and has participated on the advisory board of Abbott, Alnylam, Anthos, Bristol Myers Squibb, Sanofi, and Takeda, outside of the submitted work. Dr Kanthi is an inventor on a pending patent application by the University of Michigan on the use of biogases in vascular disease (US202201670756A1); and is supported by the National Heart, Lung, and Blood Institute Intramural Research Program and the Lasker Foundation. Dr Krumholz has received (within the last 3 years) expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Reality Labs, Tesseract/4Catalyst, F-Prime, the Siegfried and Jensen Law Firm, the Arnold and Porter Law Firm, and the Martin/Baughman Law Firm; is a cofounder of Refactor Health, an enterprise health care artificial intelligence–augmented data management company, and HugoHealth, a personal health information platform; and is associated with contracts through Yale University from Johnson and Johnson. Dr Middeldorp has received grants and personal fees from Daiichi-Sankyo; has received grants and personal fees from Bayer, Pfizer, and Boehringer Ingelheim; and has received personal fees from Portola/Alexion, Abbvie, Bristol Myers Squibb Pfizer, Norgine, and Viatris, all paid to her institution. Dr Falanga has received honoraria/consulting fees from Stago, Sanofi, Daiichi-Sankyo, Leo Pharma, and Pfizer. Dr Goldhaber has received research support from Bayer, Bristol Myers Squibb, Boston Scientific BTG EKOS, Janssen, National Heart, Lung, and Blood Institute, and Pfizer; and has received consulting fees from Agile, Bayer, and Pfizer. Dr Bikdeli is a consulting expert, on behalf of the plaintiff, for litigation related to 2 specific brand models of IVC filters; and is supported by the Scott Schoen and Nancy Adams IGNITE Award from the Mary Horrigan Connors Center for Women's Health and Gender Biology at Brigham and Women's Hospital and a Career Development Award from the American Heart Association and VIVA Physicians (#938814). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. All rights reserved.)

Background: Elderly patients undergoing hip or knee arthroplasty are at a risk for myocardial injury after noncardiac surgery (MINS). We evaluated the ability of five common cardiac risk scores, alone or combined with baseline high-sensitivity cardiac troponin I (hs-cTnI), in predicting MINS and postoperative day 2 (POD2) hs-cTnI levels in patients undergoing elective total hip or knee arthroplasty., Methods: This study is ancillary to the Genetics-InFormatics Trial (GIFT) of Warfarin Therapy to Prevent Deep Venous Thrombosis, which enrolled patients 65 years and older undergoing elective total hip or knee arthroplasty. The five cardiac risk scores evaluated were the atherosclerotic cardiovascular disease calculator (ASCVD), the Framingham risk score (FRS), the American College of Surgeon's National Surgical Quality Improvement Program (ACS-NSQIP) calculator, the revised cardiac risk index (RCRI), and the reconstructed RCRI (R-RCRI)., Results: None of the scores predicted MINS in women. Among men, the ASCVD ( C -statistic of 0.66; p =0.04), ACS-NSQIP ( C -statistic of 0.69; p =0.01), and RCRI ( C -statistic of 0.64; p =0.04) predicted MINS. Among all patients, spearman correlations ( r s ) of the risk scores with the POD2 hs-cTnI levels were 0.24, 0.20, 0.11, 0.11, and 0.08 for the ASCVD, Framingham, ACS-NSQIP, RCRI, and R-RCRI scores, respectively, with p values of <0.001, <0.001, <0.001, 0.006, and 0.025. Baseline hs-cTnI predicted MINS ( C -statistics: 0.63 in women and 0.72 in men) and postoperative hs-cTnI ( r s  = 0.51, p =0.001)., Conclusion: In elderly patients undergoing elective hip or knee arthroplasty, several of the scores modestly predicted MINS in men and correlated with POD2 hs-cTnI., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Merih T. Tesfazghi et al.)

Background: Structured reporting is an efficient and replicable method of presenting diagnostic results that eliminates variability inherent in narrative descriptive reporting and may improve clinical decisions. Synoptic element reporting can generate discrete coded data that then may inform clinical decision support and trigger downstream actions in computerized electronic health records., Objective: Limited evidence exists for use of synoptic reporting for computed tomography pulmonary arteriography (CTPA) among patients suspected of pulmonary embolism. We reported the accuracy of synoptic reporting for the outcome of pulmonary embolism among patients who presented to an integrated health care system with CTPA performed for suspected pulmonary embolism., Methods: Structured radiology reports with embedded synoptic elements were implemented for all CTPA examinations on March 1, 2018. Four hundred CTPA reports between January 4, 2019 and July 30, 2020 (200 reports each for which synoptic reporting recorded the presence or absence of pulmonary embolism [PE]) were selected at random. One non-diagnostic study was excluded from analysis. We then assessed the accuracy of synoptic reporting compared with the gold standard of manual chart review., Results: Synoptic reporting and manual review agreed in 99.2% of patients undergoing CTPA for suspected PE, agreed on the presence of PE in 196 of 199 (98.5%) cases, the absence of PE in 200 of 200 (100%) cases with a sensitivity of 87.6% (76.1-96.1) a specificity of 99.9% (99.7%-100%), a positive predictive value of 99.5% (98.1-100), and a negative predictive value of 98% (95.7%-99.5%)., Conclusion: The overall rate of agreement was 99.2%, but we observed an unacceptable false-negative rate for clinical reliance on synoptic element reporting in isolation from dictated reports., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

Background: Atrial fibrillation (AF) is associated with a risk for cognitive impairment and dementia, which is more pronounced in patients with a history of clinical stroke. Anticoagulation use and efficacy impact long-term risk of dementia in AF patients in observational trials., Methods: The cognitive decline and dementia in patients with non-valvular atrial fibrillation (CAF) Trial was a randomized, prospective, open-label vanguard clinical study with blinded endpoint assessment involving patients with moderate- to high-risk (CHADS2 or CHA2DS2-Vasc scores of ≥2) non-valvular AF assigned to dabigatran etexilate or warfarin. The primary endpoint was incident dementia or moderate cognitive decline at 24 months., Results: A total of 101 patients were enrolled [mean age:73.7 ± 6.0 years, male: 54(53.5%)]. Prior stroke and stroke risk factors were similar between groups. Average INR over the study was 2.41 ± 0.68 in the warfarin group. No patient experienced a stroke or developed dementia. Mini-Mental Status Evaluation, Hachinski Ischemic scale, cognitive subscale of the Alzheimer's Disease Assessment Scale, Disability Assessment for Dementia, Quality of Life Improvement as assessed by Minnesota Living with Heart Failure Scale and the Anti-Clot Treatment Scale Quality of Life Survey scores did not vary at baseline or change over 2 years. Biomarker analysis indicated a similar efficacy of anticoagulation strategies., Conclusion: Use of dabigatran and well-managed warfarin therapy were associated with similar risks of stroke, cognitive decline, and dementia at 2 years, suggestive that either strategy is acceptable. The results of this Vanguard study did not support the pursuit of a larger formally powered study., Competing Interests: TJB: Research grants: Altathera, Boehinger Ingelheim, Boston Scientific, Heartline Study Steering Committee for Janssen Scientific Affairs/Johnson & Johnson, HM: None, MJC: Heartline Study Steering Committee for Janssen Scientific Affairs/Johnson & Johnson, SCW: None, VJ: None, SMS: None, JC: None, KUK: none, JBM: None, BAS: National Heart, Lung, And Blood Institute of the National Institutes of Health (#K23HL143156), and reports research support from Abbott, Boston Scientific, and Janssen; and consulting to Janssen, AltaThera, Merit Medical, and Bayer; and speaking for NACCME (funded by Sanofi), JLA: None., (© 2022 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Background: Thrombosis is reported to occur more often among patients with COVID-19 than otherwise expected in the setting of viral pneumonia and sepsis. Systemic inflammatory biomarkers may be associated with venous thromboembolism (VTE) risk. The ISTH subcommittee on Predictive and Diagnostic Variables in Thrombotic Disease aimed to report the evidence on prognostic biomarkers for VTE in hospitalized patients with COVID-19., Methods: Using a standardized Preferred Reporting Items for Systematic Reviews and Meta-analysis methodology, we conducted a systematic literature review to identify studies reporting prognostic biomarkers for VTE among hospitalized patients with COVID-19. Eligible studies included adults hospitalized with COVID-19 and reported the prognostic associations between any biomarker measured on admission, and the subsequent diagnosis of deep vein thrombosis or pulmonary embolism. Two authors reviewed titles and abstracts, and three authors extracted study data and performed review of bias. Results were displayed descriptively. Meta-analysis was not possible., Results: From the initial 196 identified studies, full-text review was performed for 72 studies. Admission D-dimer levels were associated with VTE during hospitalization in five studies, and elevated platelet count was associated with VTE during hospitalization in one study. The risk of bias ranged from low to high for included studies. Overall, there was a paucity of high-quality prognostic studies. Studies on other biomarkers did not meet the systematic review inclusion criteria., Conclusions: Admission D-dimer was associated with VTE diagnosis during hospitalization for COVID-19; however, prospective validation of this finding is needed to identify optimal D-dimer thresholds to guide VTE prophylaxis measures., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

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., (© 2022 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Background: Venous thromboembolism (VTE) risk is increased in patients with COVID-19 infection. Understanding which patients are likely to develop VTE may inform pharmacologic VTE prophylaxis decision making. The hospital-associated venous thromboembolism-Intermountain Risk Score (HA-VTE IMRS) and the hospital-associated major bleeding-Intermountain Risk Score (HA-MB IMRS) are risk scores predictive of VTE and bleeding that were derived from only patient age and data found in the complete blood count (CBC) and basic metabolic panel (BMP)., Objectives: We assessed the HA-VTE IMRS and HA-MB IMRS for predictiveness of 90-day VTE and major bleeding, respectively, among patients diagnosed with COVID-19, and further investigated if adding D-dimer improved these predictions. We also reported 30-day outcomes., Patients/methods: We identified 5047 sequential patients with a laboratory confirmed diagnosis of COVID-19 and a CBC and BMP between 2 days before and 7 days following the diagnosis of COVID-19 from March 12, 2020, to February 28, 2021. We calculated the HA-VTE IMRS and the HA-MB IMRS for all patients. We assessed the added predictiveness of D-dimer obtained within 48 hours of the COVID test., Results: The HA-VTE IMRS yielded a c-statistic of 0.70 for predicting 90-day VTE and adding D-dimer improved the c-statistic to 0.764 with the corollary sensitivity/specificity/positive/negative predictive values of 49.4%/75.7%/6.7%/97.7% and 58.8%/76.2%/10.9%/97.4%, respectively. Among hospitalized and ambulatory patients separately, the HA-VTE IMRS performed similarly. The HA-MB IMRS predictiveness for 90-day major bleeding yielded a c-statistic of 0.64., Conclusion: The HA-VTE IMRS and HA-MB IMRS predict 90- and 30-day VTE and major bleeding among COVID-19 patients. Adding D-dimer improved the predictiveness of the HA-VTE IMRS for VTE., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Background: The direct oral anticoagulants (DOACs), apixaban and rivaroxaban, have been studied for extended-phase treatment of venous thromboembolism (VTE). Yet, scant evidence exists surrounding clinician practice and decision-making regarding dose reduction., Aims: Report clinician practice and characteristics surrounding dose reduction of DOACs for extended-phase VTE treatment., Methods: We conducted a 16-question REDCap survey between July 14, 2021, and September 13, 2021, among ISTH 2021 Congress attendees and on Twitter. We explored factors associated with dose reduction using logistic regression. We used k-means clustering to identify distinct groups of dose-reduction decision-making. Random forest analysis explored demographics with respect to identified groups., Results: Among 171 respondents, most were attending academic physicians from North America. Clinicians who treated larger volumes of patients had higher odds of dose reduction. We identified five clusters that showed distinct patterns of behavior regarding dose reduction. Cluster 1 rarely dose reduces and likely prescribes rivaroxaban over apixaban; cluster 2 dose reduces frequently, does not consider age when dose-reducing, is least likely to temporarily reescalate dosing, and prescribes apixaban and rivaroxaban equally; cluster 3 dose reduces <50% of the time, and temporarily reescalates dosing during increased VTE risk; cluster 4 dose reduces frequently, temporarily reescalates dosing, and is most likely to prescribe apixaban over rivaroxaban; and cluster 5 dose reduces most frequently, and takes the fewest risk factors into consideration when deciding to dose reduce., Conclusions: Most clinicians elect to dose-reduce DOACs for extended-phase anticoagulation. The likelihood of a clinician to dose reduce increases with volume of patients treated. Clinician prescribing patterns cluster around VTE risk factors as well as reescalation during high-risk periods., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Objectives: The Intermountain Risk Score (IMRS), composed using published sex-specific weightings of parameters in the complete blood count (CBC) and basic metabolic profile (BMP), is a validated predictor of mortality. We hypothesised that IMRS calculated from prepandemic CBC and BMP predicts COVID-19 outcomes and that IMRS using laboratory results tested at COVID-19 diagnosis is also predictive., Design: Prospective observational cohort study., Setting: Primary, secondary, urgent and emergent care, and drive-through testing locations across Utah and in sections of adjacent US states. Viral RNA testing for SARS-CoV-2 was conducted from 3 March to 2 November 2020., Participants: Patients aged ≥18 years were evaluated if they had CBC and BMP measured in 2019 and tested positive for COVID-19 in 2020., Primary and Secondary Outcome Measures: The primary outcome was a composite of hospitalisation or mortality, with secondary outcomes being hospitalisation and mortality separately., Results: Among 3883 patients, 8.2% were hospitalised and 1.6% died. Subjects with low, mild, moderate and high-risk IMRS had the composite endpoint in 3.5% (52/1502), 8.6% (108/1256), 15.5% (152/979) and 28.1% (41/146) of patients, respectively. Compared with low-risk, subjects in mild-risk, moderate-risk and high-risk groups had HR=2.33 (95% CI 1.67 to 3.24), HR=4.01 (95% CI 2.93 to 5.50) and HR=8.34 (95% CI 5.54 to 12.57), respectively. Subjects aged <60 years had HR=3.06 (95% CI 2.01 to 4.65) and HR=7.38 (95% CI 3.14 to 17.34) for moderate and high risks versus low risk, respectively; those ≥60 years had HR=1.95 (95% CI 0.99 to 3.86) and HR=3.40 (95% CI 1.63 to 7.07). In multivariable analyses, IMRS was independently predictive and was shown to capture substantial risk variation of comorbidities., Conclusions: IMRS, a simple risk score using very basic laboratory results, predicted COVID-19 hospitalisation and mortality. This included important abilities to identify risk in younger adults with few diagnosed comorbidities and to predict risk prior to SARS-CoV-2 infection., Competing Interests: Competing interests: BDH, HTM, BSR and JLA are inventors of clinical decision tools that are licensed to CareCentra and Alluceo. BDH is the principal investigator (PI) of grants related to clinical decision tools that were funded by Intermountain Healthcare’s Foundry innovation programme, the Intermountain Research and Medical Foundation, CareCentra, GlaxoSmithKline and AstraZeneca. BDH is a member of the scientific advisory board of Labme.ai. KUK is PI and BDH is a coinvestigator of a grant funded by the Patient-Centered Outcomes Research Institute. IDP was supported by a grant from the National Institute of General Medical Sciences (K23GM129661). Outside the current work, IDP has received grant support from the National Institutes of Health, Centers for Disease Control and Prevention, Janssen Pharmaceuticals and Immunexpress Inc, and funding to his institution from Regeneron Pharmaceuticals. The authors have no other potential conflicts of interest to report., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Thrombotic antiphospholipid syndrome (TAPS) is characterized by venous, arterial, or microvascular thrombosis. Patients with TAPS merit indefinite anticoagulation, and warfarin has historically been the standard treatment. Apixaban is an oral factor Xa inhibitor anticoagulant that requires no dose adjustment or monitoring. The efficacy and safety of apixaban compared with warfarin for TAPS patients remain unknown. This multicenter prospective randomized open-label blinded endpoint study assigned anticoagulated TAPS patients to apixaban or warfarin (target international normalized ratio 2-3) for 12 months. The primary efficacy outcome was clinically overt thrombosis and vascular death. Apixaban was first given at 2.5 mg twice daily. Two protocol changes were instituted based on recommendations from the data safety monitoring board. After the twenty-fifth patient was randomized, the apixaban dose was increased to 5 mg twice daily, and after the thirtieth patient was randomized, subjects with prior arterial thrombosis were excluded. Primary outcomes were adjudicated by independent experts blinded to treatment allocation. Patients randomized between 23 February 2015 and 7 March 2019 to apixaban (n = 23) or warfarin (n = 25) were similar. Among the components of the primary efficacy outcome, only stroke occurred in 6 of 23 patients randomized to apixaban compared with 0 of 25 patients randomized to warfarin. The study ended prematurely after the forty-eighth patient was enrolled. Conclusions from our study are limited due to protocol modifications and low patient accrual. Despite these limitations, our results suggest that apixaban may not be routinely substituted for warfarin to prevent recurrent thrombosis (especially strokes) among patients with TAPS. This trial was registered at www.clinicaltrials.gov as #NCT02295475., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Objective: To derive and validate a D-dimer cutoff for ruling out pulmonary embolism (PE) in COVID-19 patients presenting to the emergency department (ED)., Methods: A retrospective cohort study was performed in an integrated healthcare system including 22 adult ED's between March 1, 2020, and January 31, 2021. Results were validated among patients enrolled in the RECOVER Registry, representing data from 154 ED's from 26 US states. Consecutive ED patients with laboratory confirmed COVID-19, a D-dimer performed within 48 h of ED arrival, and with objectively confirmed PE were compared to those without PE. After identifying a D-dimer threshold at which the 95% confidence lower bound of the negative predictive value for PE was higher than 98% in the derivation cohort, it was validated using RECOVER registry data., Results: Among 3978 patients with a D-dimer result, 3583 with confirmed COVID-19 infection were included in the derivation cohort. Overall, PE incidence was 4.1% and a D-dimer cutoff of < 2 μ/mL (2000 ng/mL) was associated with a NPV of 98.5% (95% CI = 98.0%-98.9%). In the validation cohort of 13,091 patients with a D-dimer, 7748 had confirmed COVID-19 infection, and the PE incidence was 1.14%. A D-dimer cutoff of < 2 μ/mL was associated with a NPV of 99.5% (95% CI = 99.3%-99.7%)., Conclusion: A D-dimer cutoff of < 2 μ/ml was associated with a high negative predictive value for PE among patients with COVID-19. However, the resultant sensitivity for PE result at that threshold without pre-test probability assessment would be considered clinically unsafe.

Background: This is the 2nd update to the 9th edition of these guidelines. We provide recommendations on 17 PICO (Population, Intervention, Comparator, Outcome) questions, four of which have not been addressed previously., Methods: We generate strong and weak recommendations based on high-, moderate-, and low-certainty evidence, using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology., Results: The panel generated 29 guidance statements, 13 of which are graded as strong recommendations, covering aspects of antithrombotic management of VTE from initial management through secondary prevention and risk reduction of postthrombotic syndrome. Four new guidance statements have been added that did not appear in the 9th edition (2012) or 1st update (2016). Eight statements have been substantially modified from the 1st update., Conclusion: New evidence has emerged since 2016 that further informs the standard of care for patients with VTE. Substantial uncertainty remains regarding important management questions, particularly in limited disease and special patient populations., (Copyright © 2021. Published by Elsevier Inc.)

Background: This is the 2nd update to the 9th edition of these guidelines. We provide recommendations on 17 PICO (Population, Intervention, Comparator, Outcome) questions, four of which have not been addressed previously., Methods: We generate strong and weak recommendations based on high-, moderate-, and low-certainty evidence, using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology., Results: The panel generated 29 guidance statements, 13 of which are graded as strong recommendations, covering aspects of antithrombotic management of VTE from initial management through secondary prevention and risk reduction of postthrombotic syndrome. Four new guidance statements have been added that did not appear in the 9th edition (2012) or 1st update (2016). Eight statements have been substantially modified from the 1st update., Conclusion: New evidence has emerged since 2016 that further informs the standard of care for patients with VTE. Substantial uncertainty remains regarding important management questions, particularly in limited disease and special patient populations., (Copyright © 2021. Published by Elsevier Inc.)

Both time in therapeutic range (TTR) for anticoagulation and depression are associated with dementia risk. The purposes of this study were to examine the impact of depression on TTR and to describe the partitioned contribution of depression and TTR on long-term dementia risk. We studied 14,953 patients anticoagulated with warfarin (target INR 2-3) for atrial fibrillation (AF), venous thromboembolism (VTE), or a mechanical heart valve from 2003 to 2015. We excluded patients with a diagnosis of dementia before or within 6 months of warfarin initiation. We examined the association of depression with TTR using finite mixture modeling and logistic regression and utilized multivariable Cox hazard regression to determine the association of TTR and depression with incident dementia at 3 and 13 years. Forty % (n = 6055) of patients were diagnosed with depression before or while on warfarin. Patients with depression had significantly lower TTR and were 1.37 times more likely to have TTR <50% than non-depressed patients (p <0.0001). During follow-up, 4.2% of patients received the diagnosis of dementia within 3 years as compared to 12% during all-time follow up. The 3-year risk of dementia was highest for patients with a ≤50% TTR regardless of depression status. The 3-year dementia risk was associated with TTR (p <0.0001) but not depression. However, for all-time dementia both TTR (p <0.0001) and depression (p <0.0001) as well as their interaction (p = 0.049) were associated with dementia. Depression increased the risk of long-term dementia by 1.69 fold (95% CI: 1.33, 2.15) for patients with the lowest TTR. Depression is prevalent in patients managed with warfarin and is associated with significant decreases in TTR. In conclusion, decreased TTR appears to increase 3-year dementia risk and both low TTR and depression interact to increase risk for all-time dementia in patients taking warfarin., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Some hospitalized medical patients experience venous thromboembolism (VTE) following discharge. Prophylaxis extended beyond hospital discharge (extended duration thromboprophylaxis [EDT]) may reduce this risk. However, EDT is costly and can cause bleeding, so selecting appropriate patients is essential. We formerly reported the performance of a mortality risk prediction score (Intermountain Risk Score [IMRS]) that was minimally predictive of 90-day hospital-associated venous thromboembolism (HA-VTE) and major bleeding (HA-MB). We used the components of the IMRS to calculate de novo risk scores to predict 90-day HA-VTE (HA-VTE IMRS) and major bleeding (HA-MB IMRS)., Methods: From 45 669 medical patients we randomly assigned 30 445 to derive the HA-VTE IMRS and the HA-MB IMRS. Backward stepwise regression and bootstrapping identified predictor covariates from the blood count and basic chemistry. These candidate variables were split into quintiles, and the referent quintile was that with the lowest event rate for HA-VTE and HA-MB; respectively. A clinically relevant rate of HA-VTE and HA-MB was used to inform outcome rates. Performance was assessed in the derivation set of 15 224 patients., Results: The HA-VTE IMRS and HA-MB IMRS area under the receiver operating curve (AUC) in the derivation set were 0.646, and 0.691, respectively. In the validation set, the HA-VTE IMRS and HA-MB IMRS AUCs were 0.60 and 0.643., Conclusions: Risk scores derived from components of routine labs ubiquitous in clinical care identify patients that are at risk for 90-day postdischarge HA-VTE and major bleeding. This may identify a subset of patients with high HA-VTE risk and low HA-MB risk who may benefit from EDT., (© 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Objective: Multiple professional societies recommend pre-test probability (PTP) assessment prior to imaging in the evaluation of patients with suspected pulmonary embolism (PE), however, PTP testing remains uncommon, with imaging occurring frequently and rates of confirmed PE remaining low. The goal of this study was to assess the impact of a clinical decision support tool embedded into the electronic health record to improve the diagnostic yield of computerized tomography pulmonary angiography (CTPA) in suspected patients with PE in the emergency department (ED)., Methods: Between July 24, 2014 and December 31, 2016, 4 hospitals from a healthcare system embedded an optional electronic clinical decision support system to assist in the diagnosis of pulmonary embolism (ePE). This system employs the Pulmonary Embolism Rule-out Criteria (PERC) and revised Geneva Score (RGS) in series prior to CT imaging. We compared the diagnostic yield of CTPA) among patients for whom the physician opted to use ePE versus the diagnostic yield of CTPA when ePE was not used., Results: During the 2.5-year study period, 37,288 adult patients were eligible and included for study evaluation. Of eligible patients, 1949 of 37,288 (5.2%) were enrolled by activation of the tool. A total of 16,526 CTPAs were performed system-wide. When ePE was not engaged, CTPA was positive for PE in 1556 of 15,546 scans for a positive yield of 10.0%. When ePE was used, CTPA identified PE in 211 of 980 scans (21.5% yield) ( P  < 0.001)., Conclusions: ePE significantly increased the diagnostic yield of CTPA without missing 30-day clinically overt PE., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

Background: Although guidelines are established for the prevention and management of venous thromboembolism (VTE) in trauma, no consensus exists regarding protocols for the diagnostic approach. We hypothesized that at-risk trauma patients who undergo duplex ultrasound (DUS) surveillance for lower extremity deep venous thrombosis (DVT) will have a lower rate of symptomatic or fatal pulmonary embolism (PE) than those who do not undergo routine surveillance., Methods: Prospective, randomized trial between March 2017 and September 2019 of trauma patients admitted to a single, level 1 trauma center, with a risk assessment profile score of ≥5. Patients were randomized to receive either bilateral lower extremity DUS surveillance on days 1, 3, and 7 and weekly during hospitalization ultrasound group (US) or no surveillance no ultrasound group (NoUS). Rates of in-hospital and 90-day DVT and PE were reported as was DVT propagation and all-cause mortality. Standard care for the prevention and management of VTE per established institutional protocols was provided to all patients., Results: A total of 3,236 trauma service admissions were screened, and 1,989 moderate- and high-risk patients were randomized (US, 995; NoUS, 994). The mean ± SD age was 62 ± 20.1 years, Injury Severity Score was 14 ± 9.7, risk assessment profile was 7.1 ± 2.4, and 97% suffered blunt trauma. There was no difference in demographics or VTE risk factors between the groups. There were significantly fewer in-hospital PE in the US group than the NoUS group (1 [0.1%] vs. 9 [0.9%], p = 0.01). The US group experienced more in-hospital below-knee DVTs (124 [12.5%] vs. 8 [0.8%], p < 0.001) and above-knee DVTs (19 [1.9%] vs. 8 [0.8%], p = 0.05). There was no difference in 90-day PE or DVT, or overall mortality., Conclusion: The implementation of a selective routine DUS protocol was associated with significantly fewer in-hospital PE. More DVTs were identified with routine screening; however, surveillance bias appears to exist primarily with distal DVT. Larger trials are needed to further characterize the relationship between routine DUS screening and VTE outcomes in the high-risk trauma population., Level of Evidence: Therapeutic/care management, level II., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Evaluate the cost-effectiveness and difference in length-of-stay when patients in the ED diagnosed with low-risk pulmonary embolism (PE) are managed with early discharge or observation., Methods: Single cohort prospective management study from January 2013 to October 2016 of patients with PE diagnosed in the ED and evaluated for a primary composite endpoint of mortality, recurrent venous thromboembolism, and/or major bleeding event at 90 days. Low-risk patients had a PE Severity Index score < 86, no evidence of proximal deep vein thrombosis on venous compression ultrasonography of both lower extremities, and no evidence of right heart strain on echocardiography. Patients were managed either in the ED or in the hospital on observation status. Primary outcomes were total length of stay, total encounter costs, and 30-day costs., Results: 213 patients were enrolled. 13 were excluded per the study protocol. Of the remaining 200, 122 were managed with emergency department observation (EDO) and 78 with hospital observation (HO). One patient managed with EDO met the composite outcome due to a major bleeding event on day 61. The mean length of stay for EDO was 793.4 min (SD -169.7, 95% CI:762-823) and for HO was 1170 (SD -211.4, 95% CI:1122-1218) with a difference of 376.8 (95% CI: 430-323, p < 0.0001). Total encounter mean costs for EDO were $1982.95 and $2759.59 for HO, with a difference of $776.64 (95% CI: 972-480, p > 0.0001). 30-day total mean costs for EDO were $2864.14 and $3441.52 for HO, with a difference of $577.38 (95% CI: -1372-217, p = 0.15)., Conclusions: Patients with low-risk PE managed with ED-based observation have a shorter length of stay and lower total encounter costs than patients managed with Hospital-based observation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Real-time identification of venous thromboembolism (VTE), defined as deep vein thrombosis (DVT) and pulmonary embolism (PE), can inform a healthcare organization's understanding of these events and be used to improve care. In a former publication, we reported the performance of an electronic medical record (EMR) interrogation tool that employs natural language processing (NLP) of imaging studies for the diagnosis of venous thromboembolism. Because we transitioned from the legacy electronic medical record to the Cerner product, iCentra, we now report the operating characteristics of the NLP EMR interrogation tool in the new EMR environment. Two hundred randomly selected patient encounters for which the imaging report assessed by NLP that revealed VTE was present were reviewed. These included one hundred imaging studies for which PE was identified. These included computed tomography pulmonary angiography-CTPA, ventilation perfusion-V/Q scan, and CT angiography of the chest/ abdomen/pelvis. One hundred randomly selected comprehensive ultrasound (CUS) that identified DVT were also obtained. For comparison, one hundred patient encounters in which PE was suspected and imaging was negative for PE (CTPA or V/Q) and 100 cases of suspected DVT with negative CUS as reported by NLP were also selected. Manual chart review of the 400 charts was performed and we report the sensitivity, specificity, positive and negative predictive values of NLP compared with manual chart review. NLP and manual review agreed on the presence of PE in 99 of 100 cases, the presence of DVT in 96 of 100 cases, the absence of PE in 99 of 100 cases and the absence of DVT in all 100 cases. When compared with manual chart review, NLP interrogation of CUS, CTPA, CT angiography of the chest, and V/Q scan yielded a sensitivity = 93.3%, specificity = 99.6%, positive predictive value = 97.1%, and negative predictive value = 99%.

Antiphospholipid syndrome (APS), an acquired autoimmune thrombophilia, is characterised by thrombosis and/or pregnancy morbidity in association with persistent antiphospholipid antibodies. The 16th International Congress on Antiphospholipid Antibodies Task Force on APS Treatment Trends reviewed the current status with regard to existing and novel treatment trends for APS, which is the focus of this Task Force report. The report addresses current treatments and developments since the last report, on the use of direct oral anticoagulants in patients with APS, antiplatelet agents, adjunctive therapies (hydroxychloroquine, statins and vitamin D), targeted treatment including rituximab, belimumab, and anti-TNF agents, complement inhibition and drugs based on peptides of beta-2-glycoprotein I. In addition, the report summarises potential new players, including coenzyme Q10, adenosine receptor agonists and adenosine potentiation. In each case, the report provides recommendations for clinicians, based on the current state of the art, and suggests a clinical research agenda. The initiation and development of appropriate clinical studies requires a focus on devising suitable outcome measures, including a disease activity index, an optimal damage index, and a specific quality of life index.

Background: A previous individual participant data (IPD) meta-analysis showed that the Wells rule and D-dimer testing cannot exclude suspected deep vein thrombosis (DVT) in cancer patients., Objectives: To explore reasons for this reduced diagnostic accuracy and to optimize the diagnostic pathway for cancer patients suspected of DVT., Patients and Methods: Using IPD from 13 studies in patients with suspected DVT, DVT prevalence and the predictive value of the Wells rule items and D-dimer testing were compared between patients with and without cancer. Next, we developed a prediction model with five variables selected from all available diagnostic predictors., Results: Among the 10 002 suspected DVT patients, there were 834 patients with cancer. The median prevalence of DVT in these patients with cancer was 37.5% (interquartile range [IQR], 30.8-45.5), whereas it was 15.1% (IQR, 11.5-16.7) in patients without cancer. Diagnostic performance of individual Wells rule items and D-dimer testing was similar across patients with and without cancer, except "immobility" and "history of DVT." The newly developed rule showed a pooled c-statistic 0.80 (95% confidence interval [CI], 0.75-0.83) and good calibration. However, using this model, still only 4.3% (95% CI, 3.0-5.7) of the suspected patients with cancer could be identified with a predicted DVT posttest probability of <2%., Conclusions: Likely because of the high prevalence of DVT, clinical models followed by D-dimer testing fail to rule out DVT efficiently in cancer patients suspected of DVT. Direct referral for compression ultrasonography appears to be the preferred approach for diagnosis of suspected DVT in cancer patients., (© 2020 International Society on Thrombosis and Haemostasis.)

Clarity and guidance is required with regard to the use of direct oral anticoagulants in antiphospholipid syndrome (APS) patients, within the confines of the recent European Medicines Agency recommendations, discrepant recommendations in other international guidelines and the limited evidence base. To address this, the Lupus Anticoagulant/Antiphospholipid Antibodies Scientific and Standardization Committee (SSC) chair and co-chairs together with SSC Control of Anticoagulation members propose guidance for healthcare professionals to help them manage APS patients. Uncertainty in this field will be addressed. This guidance will also serve as a call and focus for research., (© 2020 International Society on Thrombosis and Haemostasis.)

Risk assessment models (RAMs) for venous thromboembolism (VTE) and bleeding in hospitalized medical patients inform appropriate use of thromboprophylaxis. Our aim was to use a novel approach for selecting risk factors for VTE and bleeding to be included in RAMs. First, we used the results of a systematic review of all candidate factors. Second, we used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of the evidence for the identified factors. Third, we using a structured approach to select factors to develop the RAMs, by building on clinical and methodological expertise. The expert panel made judgments on whether to include, potentially include, or exclude risk factors, according to domains of the GRADE approach and the Delphi method. The VTE RAM included age >60 years, previous VTE, acute infections, immobility, acute paresis, active malignancy, critical illness, and known thrombophilia. The bleeding RAM included age ≥65 years, renal failure, thrombocytopenia, active gastroduodenal ulcers, hepatic disease, recent bleeding, and critical illness. We identified acute infection as a factor that was not considered in widely used RAMs. Also, we identified factors that require further research to confirm or refute their importance in a VTE RAM (eg, D-dimer). We excluded autoimmune disease which is included in the IMPROVE (International Medical Prevention Registry on Venous Thromboembolism) bleeding RAM. Our results also suggest that sex, malignancy, and use of central venous catheters (factors in the IMPROVE bleeding RAM) require further research. In conclusion, our study presents a novel approach to systematically identifying and assessing risk factors to be included or further explored during RAM development., (© 2020 by The American Society of Hematology.)

Background: Discharged medical patients are at risk for venous thromboembolism (VTE). It is difficult to identify which discharged patients would benefit from extended duration thromboprophylaxis. The Intermountain Risk Score is a prediction score derived from discrete components of the complete blood cell count and basic metabolic panel and is highly predictive of 1-year mortality. We sought to ascertain if the Intermountain Risk Score might also be predictive of 90-day postdischarge hospital-associated VTE (HA-VTE)., Methods: We applied the Intermountain Risk Score to 60 064 medical patients who survived 90 days after discharge and report predictiveness for HA-VTE. Area under the receiver operating curve analyses were performed. We then assessed whether the Intermountain Risk Score improved prediction of 2 existing VTE risk assessment models., Results: The Intermountain Risk Score poorly predicted HA-VTE (area under the curve = 0.58; 95% confidence interval [CI], 0.56-0.60). Each clinical risk assessment model was superior to the Intermountain Risk Score (UTAH area under the curve, 0.63; Kucher area under the curve, 0.62; Intermountain Risk Score area under the curve, 0.58; P  < .001 for each comparison). Adding the Intermountain Risk Score to these scores did not substantially improve the performance of either risk assessment model (UTAH + Intermountain Risk Score, 0.65; Kucher + Intermountain Risk Score, 0.64)., Conclusion: The Intermountain Risk Score demonstrated poor predictiveness for HA-VTE when compared to existing risk assessment models. Adding the Intermountain Risk Score to existing risk assessment models did not improve upon either risk assessment model alone to justify the added complexity., (© 2020 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Background: Syncope occurs in 1 in 4 people during their lifetime and accounts for 1% to 1.5% of emergency department (ED) visits. Most causes of syncope are benign, but syncope may be caused by life-threatening conditions including pulmonary embolism (PE) in up to 2% of cases. A recent publication reported the prevalence of PE in patients with syncope to be over 17%., Aims: We sought to determine the frequency and diagnostic yield of testing for PE in patients presenting to the ED with syncope in our large, integrated health care system., Methods: We performed a retrospective, longitudinal cohort study of patients who presented with syncope to EDs within a 21-hospital integrated health care system from 2010 to 2015 to find the frequency and diagnostic yield of testing for PE in patients with syncope at index ED visit and within 180 days afterward., Results: We screened 2 749 371 ED encounters to find 32 440 (1.2%) with syncope. Median age was 52 (interquartile range, 31-71), 57.5% were female, and 90% were Caucasian. PE was diagnosed on the index ED visit in 259 (0.8%; 95% confidence interval [CI], 0.7%-0.9%) cases. Assessment for suspected PE with D-dimer occurred in 5089 (15.7%) patients, and 2338 (7.2%) underwent computed tomography pulmonary angiography (CTPA). The yield of CTPA was 7.9%. PE was detected in 2.2% in whom a D-dimer was performed. From index visit to 180 days, 467 (1.4%; 95% CI, 1.3%-1.6%) patients were diagnosed with a PE, and 1051 (3.2%, 95% CI, 3.0%-3.4%) patients died., Conclusion: Diagnostic testing for PE is frequent in patients with syncope presenting to the EDs of a large, integrated health care system. The yield of diagnostic testing is low., (© 2019 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals, Inc on behalf of International Society on Thrombosis and Haemostasis.)

Importance: The optimal international normalized ratio (INR) to prevent venous thromboembolism (VTE) in warfarin-treated patients with recent arthroplasty is unknown., Objective: To determine the safety and efficacy of a target INR of 1.8 vs 2.5 for VTE prophylaxis after orthopedic surgery., Design, Setting, and Participants: The randomized Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis enrolled 1650 patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016., Interventions: In a 2 × 2 factorial design, participants were randomized to a target INR of 1.8 (n = 823) or 2.5 (n = 827) and to either genotype-guided or clinically guided warfarin dosing. For the first 11 days of therapy, open-label warfarin dosing was guided by a web application., Main Outcomes and Measures: The primary outcome was the composite of VTE (within 60 days) or death (within 30 days). Participants underwent screening duplex ultrasound postoperatively. The hypothesis was that an INR target of 1.8 would be noninferior to an INR target of 2.5, using a noninferiority margin of 3% for the absolute risk of VTE. Secondary end points were bleeding and INR values of 4 or more., Results: Among 1650 patients who were randomized (mean age, 72.1 years; 1049 women [63.6%]; 1502 white [91.0%]), 1597 (96.8%) received at least 1 dose of warfarin and were included in the primary analysis. The rate of the primary composite outcome of VTE or death was 5.1% (41 of 804) in the low-intensity-warfarin group (INR target, 1.8) vs 3.8% (30 of 793) in the standard-treatment-warfarin group (INR target, 2.5), for a difference of 1.3% (1-sided 95% CI, -∞ to 3.05%, P = .06 for noninferiority). Major bleeding occurred in 0.4% of patients in the low-intensity group and 0.9% of patients in the standard-intensity group, for a difference of -0.5% (95% CI, -1.6% to 0.4%). The INR values of 4 or more occurred in 4.5% of patients in the low-intensity group and 12.2% of the standard-intensity group, for a difference of -7.8% (95% CI, -10.5% to -5.1%)., Conclusions and Relevance: Among older patients undergoing hip or knee arthroplasty and receiving warfarin prophylaxis, an international normalized ratio goal of 1.8 compared with 2.5 did not meet the criterion for noninferiority for risk of the composite outcome of VTE or death. However, the trial may have been underpowered to meet this criterion and further research may be warranted., Trial Registration: ClinicalTrials.gov Identifier: NCT01006733.

Background: Upper extremity deep vein thrombosis (UEDVT) constitutes approximately 10% of all deep vein thromboses (DVTs). The incidence of UEDVT is increasing in association with use of peripherally inserted central venous catheters. Treatment for UEDVT is derived largely from evidence for treatment of lower extremity DVT. Limited evidence exists for the use of a direct oral anticoagulant for the treatment of UEDVT., Population: Sequential patients identified within the Intermountain Healthcare System and University of Utah Healthcare system with symptomatic UEDVT defined as the formation of thrombus within the internal jugular, subclavian, axillary, brachial, ulnar, or radial veins of the arm., Intervention: Apixaban 10 mg PO twice daily for 7 days followed by apixaban 5 mg twice daily for 11 weeks., Comparison: The historical literature review rate of venous thrombosis reported for recurrent clinically overt objective venous thromboembolism (VTE) and VTE-related death. If the confidence interval for the observed rate excludes the threshold event rate of 4%, we will conclude that treatment with apixaban is noninferior and therefore a clinically valid approach to treat UEDVT., Sample Size: We elected a sample size of 375 patients so that an exact 95% confidence interval would exclude an event rate of VTE in the observation cohort of 4%., Outcome: Ninety-day rate of new or recurrent objectively confirmed symptomatic venous thrombosis and VTE-related death. The primary safety outcome is the composite of major and clinically relevant nonmajor bleeding.

Atrial fibrillation (AF) is associated with a risk for cognitive impairment and dementia, which is more pronounced in patients with a history of clinical stroke. Observational trials suggest that the implementation and quality of long-term anticoagulation impact dementia risk. Emerging evidence suggests that direct oral anticoagulants may improve long-term risk of dementia in AF patients. This manuscript describes the rational and trial design of the the Cognitive Decline and Dementia in Atrial Fibrillation Patients (CAF) Trial. CAF investigates if AF patients randomized to dabigatran etexilate will have long-term higher cognition scores and lower rates of dementia compared in the long term to dose-adjusted warfarin (International Normalized Ratio [INR]: 2.0-3.0). As of 27 February 2019, a total of 120 subjects will be enrolled at one investigational site in the United States and will be followed for 2 years after study enrollment. To date, 97 have been enrolled. The average age is 74.2 years, 53% are male, and 9% had a prior stroke. In this Vanguard study, patients will be followed for 2 years after study enrollment. These prospective, randomized data will inform the understanding of two anticoagulants in AF patients as it relates to risk of cognitive decline and dementia. Cranial imaging and biomarkers collected will assist in understanding mechanisms of brain injury., (© 2019 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

Background: Central venous catheters (CVC) and peripherally inserted central catheters (PICCs) are central vascular access devices (CVADs) that facilitate administration of medications among critically ill patients. Both are associated with risk of venous thromboembolism (VTE). The relative risk of VTE between these catheter types is not well defined. We report the rate of VTE in intensive care unit (ICU) medical patients receiving PICC, CVC, both, or neither., Methods: We conducted a single-center, retrospective cohort study of medical-ICU patients between November 2007 and November 2013 grouped by receipt of CVC, PICC, both, or neither. The primary outcome was the rate of 30-day symptomatic venous thrombosis (upper and lower deep vein thrombosis and pulmonary embolism). Cox modeling was used to analyze this population and adjust for comorbidities which could contribute to VTE. Secondary outcomes included VTE location, major bleeding, and all-cause mortality among patients with and without CVADs., Results: We analyzed 5788 patients. CVADs were placed in 2403 (42%) patients (PICC, n = 816; CVC, n = 1153; both, n = 434). Compared with no CVAD, the hazard ratio (HR) for 30-day VTE was 1.81 (95% CI 1.52-2.17) for any CVAD, 1.90 (95% CI 1.52-2.37) for PICC, 1.57 (95% CI 1.26-1.96) for CVC, and 2.70 (95% CI 2.09-3.47) for both. PICCs had a non-significantly higher HR for VTE compared with CVC (1.21; 95% CI 0.94-1.55). For patients with both a CVC and PICC the HR for VTE was 1.72 times that of solitary CVAD (95% CI 1.32-2.23)., Conclusions: Among critically ill medical patients, PICCs and CVCs were associated with increased risk of VTE. Placement of both conferred higher risk of VTE compared with either alone., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The efficacy and safety of managing patients with low-risk pulmonary embolism (PE) without hospitalization requires objective data from US medical centers. We sought to determine the 90-day composite rate of recurrent symptomatic VTE, major bleeding events, and all-cause mortality among consecutive patients diagnosed with acute low-risk PE managed without inpatient hospitalization; and to measure patient satisfaction., Methods: We performed a prospective cohort single-arm management study conducted from January 2013 to October 2016 in five EDs. We enrolled 200 consecutive adults diagnosed with objectively confirmed acute PE and assessed to have a low risk for mortality using the Pulmonary Embolism Severity Index (PESI) score (< 86), echocardiography, and whole-leg compression ultrasound (CUS). The primary intervention was observation in the ED or hospital (observation status) for > 12 to < 24 h, followed by outpatient management with Food and Drug Administration-approved therapeutic anticoagulation. Patients were excluded for a PESI ≥ 86, echocardiographic signs of right heart strain, DVT proximal to the popliteal vein, hypoxia, hypotension, hepatic or renal failure, contraindication to therapeutic anticoagulation, or another condition requiring hospital admission. The primary outcome was 90-day composite rate of all-cause mortality, recurrent symptomatic VTE, and major bleeding., Results: The composite outcome occurred in one of 200 patients (90-day composite rate = 0.5%; 95% CI, 0.02%-2.36%). No patient suffered recurrent VTE or died during the 90-day follow-up period. A major bleed occurred in one patient. Patients indicated a high level of satisfaction with their care., Conclusions: Treatment of carefully selected patients with acute PE and low risk by PESI < 86, echocardiography, and CUS without inpatient hospitalization is safe and acceptable to patients. Results must be viewed with caution because of the small sample size relative to the end point and the generalizability surrounding availability of emergent echocardiography., Trial Registry: ClinicalTrials.gov; No.: NCT02355548; URL: www.clinicaltrials.gov., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)