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Introduction: Factor Xa inhibitor (FXaI)-associated bleeding events are common and associated with substantial morbidity. Systematic evaluation of widely available, effective, and affordable FXaI bleed management strategies is needed., Materials and Methods: We conducted a single-center retrospective cohort study of FXaI-treated patients presenting to a tertiary academic medical center from January 2018 to May 2019 who received 25-50 IU/kg 4F-PCC for either FXaI-associated major bleeding or urgent surgery. The primary outcome was hemostatic efficacy, and the safety outcome was the 30-day risk of thromboembolism., Results: PCC was used to treat FXaI-associated bleeding in 83 cases (79.1 %) and was given before urgent surgery in 22 cases (20.9 %). Sixty-six patients were on apixaban, 38 were on rivaroxaban and one patient was on edoxaban. Intracranial hemorrhage (ICH) and gastrointestinal bleeding accounted for most bleeds (74.7 %). Median interval between last DOAC intake and presentation to triage was 9 h [IQR 5.3-14.8] and median PCC dosing was 40.0 IU/kg [IQR 28.5-46.6]. Forty-two patients (40.0 %) had pre-PCC FXaI levels drawn with median FXaI levels of 114.5 ng/mL [IQR 70.0-175.0]. Effective hemostasis occurred in 66.7 % [95%CI 55.4-76.3] of patients receiving PCC for bleeding and surgical hemostasis was rated as normal in 95.5 % (95%CI 76.5-100.0) for patients having urgent surgery. The 30-day risk of thromboembolism was 7.6 % [95%CI 3.7-14.5] and 22.9 % [95%CI 15.8-31.8] of patients died., Conclusions: PCC for FXaI-associated bleeding was associated with hemostatic efficacy in two-thirds of patients and thromboembolic events were uncommon. PCC represents a promising treatment strategy for FXaI-associated bleeding., Competing Interests: Declaration of competing interest J.R. Shaw has received in-kind laboratory support from Diagnostica Stago. J.H. Levy serves on steering committees for Merck, Octapharma, Takeda, and Werfen. S. Schulman reports research grant funding from Octapharma and honoraria from Alexion, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Regeneron, Sanofi, and Takeda. D.M. Siegal has received honoraria paid indirectly to her institution from Astra Zeneca, BMS-Pfizer, Servier. D. Dowlatshahi has provided consultation to Astra Zeneca Canada. M. Carrier has received research funding from Leo Pharma and Pfizer, in addition to honoraria from BMS, Valeo Pharma, Leo Pharma, Sanofi and Servier. L. Castellucci's research institution has received honoraria from Bayer, BMS-Pfizer Alliance, The Academy for Continued Advancement in Healthcare Education, Amag Pharmaceutical, LEO Pharma, Sanofi, Valeo Pharma, and Servier., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Post-thrombotic syndrome (PTS) is common in patients with deep vein thrombosis (DVT). It is unclear if different types of anticoagulant therapies (e.g. vitamin K antagonists (VKA), direct oral anticoagulants (DOACs) or low molecular weight heparin (LMWH)) are associated with different risks of PTS. We sought to assess the incidence rates of PTS development following a proximal DVT of the lower extremity managed with different types of anticoagulation regimens., Methods: A systematic search of MEDLINE, EMBASE and PubMed, from inception to June 2023 was performed. The primary outcome was development of PTS. The secondary outcomes included severe PTS, venous ulcers, and major bleeding. Incidence rates were pooled using the random effects model and expressed as event per 100 patient-years with its associated 95 % confidence intervals (CI) using R software., Results: A total of 21 (4342 patients) articles were included in the analysis. The adjusted pooled incidence of PTS was 15.1 (95 % CI: 8.7 to 26.1), 18.2 (95 % CI: 9.4 to 35.1) and 24.6 (95 % CI: 9.2 to 65.5) per 100 patient-years patients managed with VKA, DOAC and LMWH, respectively. The adjusted pooled incidence of severe PTS was 5.1 (95 % CI: 2.6 to 10.0) and 0.2 (95 % CI: 0.01 to 2.7) per 100 patient-years for VKAs and DOACs, respectively., Conclusions: The development of PTS is common in patients with proximal lower extremity DVT. The incidence rates of PTS seem to be similar across the different anticoagulation regimens, but severe PTS may be lower among patients receiving a DOAC., Competing Interests: Declaration of competing interest M. Carrier has received research funding from BMS, Pfizer, and Leo Pharma, and honoraria from Bayer, Pfizer, BMS, Servier, and Leo Pharma. A. Delluc reports grants from Leo Pharma and Pfizer, personal fees from BMS, Leo Pharma, Pfizer, Servier. C Brown and L Tokessy have no relevant conflicts of interest to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Approximately 10 % of all diagnosed pulmonary embolism are isolated to the subsegmental vessels. The risk of recurrent venous thromboembolism (VTE) in patients with an acute subsegmental pulmonary embolism (SSPE) managed with or without anticoagulant therapy remains poorly understood., Methods: This is an observational cohort study including consecutive adult patients diagnosed with acute isolated SSPE between June 01, 2019, and August 31, 2022. We excluded patients with a concomitant diagnosis of deep vein thrombosis and those who had an indication for long-term anticoagulation. The primary outcome was objectively confirmed recurrent VTE., Results: Overall, 118 patients with acute SSPE were included in the analysis. The mean (± standard deviation [SD]) age of the participants was 59 ± 17 years and 44 % of them had active cancer. Mean (±SD) duration of follow-up was 438 ± 426 days. Seventy-seven patients (65 %) were initially treated with anticoagulation, whereas 41 patients (35 %) were not. Of the 77 patients receiving anticoagulant therapy, 23 (30 %) received extended-duration anticoagulation (beyond 3 months) for secondary prevention. Overall, recurrent VTE events occurred in 6/118 (5 %, 95 % CI 2.4 to 10.7) patients. Four events (4/77 = 5.2 %, 95 % CI 2.0 to 12.6) occurred in initially treated patients. Two recurrent VTE occurred in patients initially left untreated (2/41 = 4.9 %, 95 % CI 1.4 to 16.1). Half of the recurrent VTE occurred in patients with active cancer., Conclusions: Most patients diagnosed with an acute SSPE received anticoagulation. The incidence of recurrent VTE detected over time was relatively high, especially in patients with cancer., Competing Interests: Declaration of competing interest L. Girardi, L. A. Ciuffini, V. Mai, D. Santagata and TF. Wang report no conflicts of interests. W. Ageno reports advisory board honoraria from Bayer, Boehringer Inghelheim, Daiichi Sankyo, BMS/Pfizer, Sanofi, and Portola, and reports research funding and personal fees from Bayer, and personal fees from BMS/Pfizer, Daiichi Sankyo, Sanofi, Aspen, Janssen, and Portola, outside the submitted work. M. Carrier has received research funding from BMS, Pfizer, and Leo Pharma, and honoraria from Bayer, Pfizer, BMS, Servier, and Leo Pharma. G. Le Gal reports advisory board honoraria from Inari, Pfizer, Sanofi. G. Le Gal holds a Chair on Diagnosis of Venous Thromboembolism at the Faculty of Medicine, University of Ottawa., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Major abdominopelvic surgery is an important risk factor for postoperative venous thromboembolism (VTE). VTE is the leading cause of 30-day postoperative mortality in patients with cancer undergoing major abdominopelvic surgery. Randomized controlled trials have shown that extended duration thromboprophylaxis using a low molecular weight heparin or a direct oral anticoagulant significantly decreases the risk of overall VTE (symptomatic events and asymptomatic deep vein thrombosis). Hence, several clinical practice guidelines suggest the use of extended duration thromboprophylaxis for all high-risk patients undergoing major abdominopelvic surgery. Despite these recommendations by clinical practice guidelines, adoption of extended duration thromboprophylaxis in clinical practice remains low and clinical equipoise seems to persist. In this narrative review, we aim is to highlight and summarize the reasons that may explain discrepancy between clinical guideline recommendations and current practice regarding extended duration thromboprophylaxis in this patient population. We also aim to review different personalized approaches based on patients' individualized risk of VTE that may foster shared decision making and improve patient outcomes by reducing decisional conflict, increasing patient knowledge, and increasing risk perception accuracy., Competing Interests: Declaration of competing interest M. Carrier has received research funding from BMS, Pfizer, and Leo Pharma, and honoraria from Bayer, Pfizer, BMS, Servier, and Leo Pharma. TF. Wang received honorarium from Servier. A Noureldin, V Ivankovic, M Delisle, TF Wang and R Auer have no relevant conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: A main concern in the management of patients with cancer-associated thrombosis (CAT) is drug-drug interactions (DDIs) between anticoagulants and anticancer therapies. Their clinical implications remain unclear., Methods: To quantify the prevalence of DDIs and risks of recurrent venous thromboembolism (VTE) and bleeding events in patients with CAT on anticoagulation, we conducted a retrospective cohort study in patients with CAT on concurrent anticoagulants and anticancer and/or supportive care therapies. All patients were followed for 6 months from CAT diagnosis or until death (whichever occurred first). The primary outcome was the percentage of patients with anticoagulant DDIs classified as risk C, D, or X in Lexicomp® at any time during the 6 months. Secondary outcomes included recurrent VTE and clinically relevant bleeding events. We calculated the 6-month cumulative incidence of outcomes with 95 % confidence interval (CI) and compared those with and without DDIs, considering death as a competing risk., Results: Among 267 patients included, 111 (41.6 %) had DDIs with anticoagulants at any time during the study. Those on DOACs at any time had more DDIs compared to LMWH (50.9 % vs 19.3 %, p < 0.0001). The 6-month incidence was 8.2 % (95 % CI 5.3-11.9) for recurrent VTE and 6.7 % (95 % CI 4.2-10.2) for clinically relevant bleeding, with no significant differences between groups with or without DDIs., Conclusions: There are high incidences of DDIs in patients with CAT on anticoagulants, more with DOACs. DDIs classified as risk C, D, or X by Lexicomp® were not associated with recurrent VTE or bleeding events in our cohort., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: T-F. Wang reports grants from LEO Pharma Inc. Canada and advisory board honoraria from Valeo. A. Delluc reports grants from LEO Pharma Inc. Canada and Pfizer, personal fees from BMS, Leo Pharma, Pfizer, Servier. M. Carrier reports grants from BMS, LEO Pharma Inc. Canada and Pfizer, personal fees from BMS, Leo Pharma, Bayer, Pfizer, Servier and Sanofi. The other authors report no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: While several risk stratification tools have been developed to predict the risk of recurrence in patients with an unprovoked venous thromboembolism (VTE), only 1 in 4 patients are categorized as low-risk. Rather than a one-time measure, serial D-dimer assessment holds promise to enhance the prediction of VTE recurrence after oral anticoagulant (OAC) cessation., Methods: Using the REVERSE cohort, we compared VTE recurrence among patients with normal D-dimer levels (<490 ng/mL among males under age 70, <500 ng/mL in others) at OAC cessation and 1-month follow-up, to those with an elevated D-dimer level at either timepoint. We also evaluated VTE recurrence based on absolute increase in D-dimer levels between the two timepoints (e.g., ∆D-dimer) according to quartiles., Results: Among 214 patients with serial D-dimer levels measured at OAC cessation and 1-month follow-up, an elevated D-dimer level at either timepoint was associated with a numerically higher risk of recurrent VTE than patients with normal D-dimer levels at both timepoints (6.9 % vs. 4.2 % per year, hazard ratio 1.6; 95 % CI 0.9-2.7). Among women with <2 HERDOO2 criteria, a normal D-dimer level at both timepoints predicted a very low risk of recurrent VTE during follow-up (0.8 % per year, 95 % CI 0.1-2.8). Irrespective of baseline value, recurrent VTE risk was only 3 % per year (95 % CI 1.4-5.6) among patients in the lowest ∆D-dimer quartile., Conclusion: Serial normal D-dimer levels have the potential to identify patients at a low risk of recurrent VTE. In addition, ∆D-dimer, irrespective of its elevation above cutoff threshold, may predict recurrent VTE., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Drs. Xu, Khan, Kovacs, Sabri, Righini, Kahn, Anderson, Chagnon, White, Rodger and Le Gal have no conflicts of interest to report. Dr. Carrier reports research funding from BMS, Leo Pharma, and Pfizer; and honoraria from Bayer, Pfizer, BMS, Leo Pharma, Servier, and Sanofi. Dr. Wells reports speaker honoraria from BMS and Bayer Healthcare and prior grant funding from BMS/Pfizer. Dr. Crowther reports honoraria from Pfizer, CSL Behring, and Diagnostica Stago; consultation services to/served on advisory boards for Servier Canada, Asahi Kasei, and Precision Biologics; serving on the data safety monitoring board for Bayer; stock ownership in Alnylam; and holds the Leo Pharma Chair in Thromboembolism research, the funding for which is held in perpetuity at McMaster University (the interest is used to support M.A.C.'s research activities)., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The prevalence of pulmonary embolism (PE) is approximately 11-17 % in patients with an acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). The optimal diagnostic strategy for PE in these patients remains undetermined., Aims: To evaluate the safety and efficacy of standard (revised Geneva and Wells PE scores combined with fixed D-dimer cut-off) and computed tomography pulmonary angiogram (CTPA)-sparing diagnostic strategies (ADJUST-PE, YEARS, PEGeD, 4PEPS) in patients with AE-COPD., Method: Post-hoc analyses of data from the multicenter prospective PEP study were performed. The primary outcome was the diagnostic failure rate of venous thromboembolism (VTE) during the entire study period. Secondary outcomes included diagnostic failure rate of PE and deep venous thrombosis (DVT), respectively, during the entire study period and the number of CTPA needed per diagnostic strategy., Results: 740 patients were included. The revised Geneva and Wells PE scores combined with fixed D-dimer cut-off had a diagnostic failure rate of VTE of 0.7 % (95%CI 0.3 %-1.7 %), but >70.0 % of the patients needed imaging. All CTPA-sparing diagnostic algorithms reduced the need for CTPAs (-10.1 % to -32.4 %, depending on the algorithm), at the cost of an increased VTE diagnosis failure rate of up to 2.1 % (95%CI 1.2 %-3.4 %)., Conclusion: Revised Geneva and Wells PE scores combined with fixed D-dimer cut-off were safe, but a high number of CTPA remained needed. CTPA-sparing algorithms would reduce imaging, at the cost of an increased VTE diagnosis failure rate that exceeds the safety threshold. Further studies are needed to improve diagnostic management in this population., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Couturaud reports having received research grant support from Bristol-Myers Squibb/Pfizer and Bayer and fees for board memberships or symposia from Bayer, Bristol-Myers Squibb/Pfizer, Merck Sharp and Dohme, Merck Sharp and Dohme, Sanofi, Leo Pharma, Janssen and Astra Zeneca and having received travel support from Bayer, Bristol-Myers Squibb/Pfizer, Leo Pharma, Pfizer. Dr. Bertoletti reports having received research grant support from Bayer and fees for board memberships or symposia from Actelion, Aspen, Bayer, Bristol-Myers Squibb/Pfizer and MSD, and having received travel support from Aspen, Bayer, Bristol-Myers Squibb/Pfizer, Daiichi Sankyo, Leo Pharma, MSD and Actelion. Dr. Pastre declares he has no conflict of interest related to this research. Dr. Roy declares he has no conflict of interest related to this research. Dr. Rambaud declares he has no conflict of interest related to this research. Dr. Mai declares she has no conflict of interest related to this research. Dr. Motreff declares she has no conflict of interest related to this research. Dr. Auffret declares he has no conflict of interest related to this research. Dr. Le Mao declares he has no conflict of interest related to this research. Dr. Gagnadoux declares he has no conflict of interest related to this research. Dr. Paleiron declares he has no conflict of interest related to this research. Dr. Schmidt declares he has no conflict of interest related to this research. Dr. Schmidt declares he has no conflict of interest related to this research. Dr. Sanchez reports having received research grant support from Bayer, Daiichi-Sankyo and Portola Pharmaceuticals, and fees or non-financial support for consultancy activities from Actelion, GlaxoSmithKline, Boehringer Ingelheim and Chiesi. Dr. Bressollette declares he has no conflict of interest related to this research. Dr. Nonent declares he has no conflict of interest related to this research. Dr. Tromeur declares she has no conflict of interest related to this research. Dr. Salaun declares he has no conflict of interest related to this research. Dr. Mismetti reports having received research grants from Bayer, fees for board memberships from Bayer, Bristol-Myers Squibb/Pfizer and Daiichi Sankyo, for lectures from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, Daiichi Sankyo and Sanofi, and for development of educational presentations from Bayer and Bristol-Myers Squibb/Pfizer. Dr. Girard reports having received personal fees and non-financial support from Bayer and Leo Pharma. Dr. Lacut reports having received personal fees from Bayer-Health Care, Bristol-Myers Squibb and Boehringer Ingelheim. Dr. Lemarie declares she has no conflict of interest related to this research. Dr. Meyer reports having received research grant support from Bayer, Boehringer Ingelheim, LEO Pharma Research Foundation and Sanofi, having been an uncompensated board member and a consultant for Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Leo Pharma and Pfizer, and having received travel support from Bayer, Boehringer Ingelheim, Daiichi Sankyo, Leo Pharma and Sanofi. Dr. Leroyer reports having received research grant support from Pfizer and fees for board memberships or symposia from Bayer and Astra Zeneca and having received travel support from Bayer, Leo Pharma. No other potential conflict of interest relevant to this article was reported., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Pharmacological thromboprophylaxis slightly increases bleeding risk. The only risk assessment model to predict bleeding in medical inpatients, the IMPROVE bleeding risk score, has never been validated using prospectively collected outcome data., Methods: We validated the IMPROVE bleeding risk score in a prospective multicenter cohort of medical inpatients. Primary outcome was in-hospital clinically relevant bleeding (CRB) within 14 days of admission, a secondary outcome was major bleeding (MB). We classified patients according to the score in high or low bleeding risk. We assessed the score's predictive performance by calculating subhazard ratios (sHRs) adjusted for thromboprophylaxis use, positive and negative predictive values (PPV, NPV), and the area under the receiver operating characteristic curves (AUC)., Results: Of 1155 patients, 8 % were classified as high bleeding risk. CRB and MB within 14 days occurred in 0.94 % and 0.47 % of low-risk and in 5.6 % and 3.4 % of high-risk patients, respectively. Adjusted for thromboprophylaxis, classification in the high-risk group was associated with an increased risk of 14-day CRB (sHR 4.7, 95 % confidence interval [CI] 1.5-14.5) and MB (sHR 4.9, 95%CI 1.0-23.4). PPV was 5.6 % and 3.4 %, while NPV was 99.1 % and 99.5 % for CRB and MB, respectively. The AUC was 0.68 (95%CI 0.66-0.71) for CRB and 0.73 (95%CI 0.71-0.76) for MB., Conclusion: The IMPROVE bleeding risk score showed moderate to good discriminatory power to predict bleeding in medical inpatients. The score may help identify patients at high risk of in-hospital bleeding, in whom careful assessment of the risk-benefit ratio of pharmacological thromboprophylaxis is warranted., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Splanchnic vein thrombosis (SVT) is an uncommon manifestation of venous thromboembolism in the splanchnic venous system, with scarce evidence surrounding its management. We assessed the efficacy and safety of direct oral anticoagulant (DOAC) to low-molecular-weight heparins (LMWH), vitamin-k antagonists (VKAs), or no anticoagulation., Methods: We conducted a systematic review and meta-analysis with the primary efficacy outcome being complete recanalization of affected vessels and primary safety outcome being major bleeding. Meta-analysis was done using a random-effects model, with dichotomous outcomes being synthesized with odds ratios (ORs) and corresponding 95 % CIs., Results: Seven non-randomized and one randomized study involving 883 participants were included for analysis. DOACs were more effective than VKAs (OR = 4.33; 95 % CI: 2.4, 7.83; n = 1 study) in non-cirrhotic patients and no anticoagulation in cirrhotic patients (OR = 3.86; 95 % CI: 1.49, 10.03; n = 3 studies). DOACs had a statistically significant reduction in major bleeding compared to observation [OR = 0.09; 95 % CI: 0.03, 0.29; n = 3 studies], LMWHs [OR = 0.13; 95 % CI: 0.03, 0.29; n = 1 study] and VKAs [OR = 0.12; 95 % CI: 0.02, 0.69; n = 2 studies] in non-cirrhotic patients. No difference in major bleeding was found between DOACs and observation, LMWH, or VKAs in cirrhotic patients., Conclusion: DOACs appear to be a favorable alternative to VKAs and LMWHs in non-cirrhotic patients. This avenue of research would benefit from larger studies that adjust for SVT etiologies, patient risk factors, and overall bleeding risk., Competing Interests: Declaration of competing interest Mr. Allen Li has received funding from the University of Ottawa and is supported by the American Society of Hematology - 2022 Hematology Opportunities for the Next Generation of Research Scientists (HONORS) Award. Dr. Ali Eshaghpour is supported by the American Society of Hematology - 2023 Hematology Opportunities for the Next Generation of Research Scientists (HONORS) Award. Dr. Marc Carrier has received support from BMS, Leo Pharma, Pfizer, Bayer, Sanofi, Servier, Leo Pharma, BMS, Pfizer and Valeo. Dr. Mark Crowther has received support from AstraZeneca, Bayer, Pfizer, Alynlam, CSL Behring, Precision Biologics, Hemostasis reference laboratories, and Syneos Health. No other authors have relevant conflicts of interests to disclose. No funding was received for the conception and design of this study., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Isolated distal deep vein thrombosis (IDDVT) is a common clinical presentation of DVT. The efficacy and safety of anticoagulant therapy for the management of IDDVT in patients with cancer are unclear. We sought to assess the incidence of recurrent venous thromboembolism (VTE) and major bleeding in this patient population., Methods: A systematic search of MEDLINE, EMBASE and PubMed, from inception to June 2, 2022 was performed. The primary efficacy outcome was recurrent VTE and the primary safety outcome was major bleeding. The secondary outcomes were clinically relevant non-major bleeding (CRNMB) and mortality. The incidence rates of thrombotic, bleeding, and mortality outcomes were pooled using random effects model and expressed as events per 100 patient-months with associated 95 % confidence intervals (CI)., Results: Out of a total of 5234 articles, 10 observational studies including 8160 patients with cancer and IDDVT were included in the analysis. The incidence rate of recurrent VTE was 5.65 (95 % CI: 2.09-15.30) per 100 patient-years regardless of type and duration of anticoagulant therapy. The incidence rate of major bleeding was 4.08 (95 % CI: 2.52-6.61) per 100 patient-years. The incidence rates for CRNMB and mortality per 100 patient-years were 8.11 (95 % CI: 5.56-11.83) and 30.22 (95 % CI: 22.60-40.42.89), respectively., Conclusion: Patients with cancer and IDDVT are at high risk of developing recurrent VTE and bleeding complications (both major bleeding and CRNMB). More studies are needed to define the optimal management for this high-risk population., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: C. Brown and W Brandt do not have any conflicts. T-F. Wang reports research funding from LEO Pharma Research Foundation and advisory honoraria from Servier. A. Delluc reports grants from LEO Pharma Research Foundation and Pfizer, personal fees from BMS, Leo Pharma, Pfizer, Servier. M. Carrier reports grants from BMS, LEO Pharma Research Foundation and Pfizer, personal fees from BMS, Leo Pharma, Bayer, Pfizer, Servier and Sanofi., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Patients with cancer have an increased risk of both venous thromboembolism (VTE) requiring anticoagulation and thrombocytopenia. The optimal management is unclear. We performed a systematic review and meta-analysis to evaluate the outcomes in these patients., Methods: We searched MEDLINE, Embase, Scopus, and Cochrane Central Register of Controlled Trials from inception to February 5, 2022. Studies assessing adult patients with cancer-associated thrombosis and platelet count <100 × 10 9 /L were included. Three anticoagulation management strategies were reported: full dose, modified dose, or no anticoagulation. The primary efficacy outcome was recurrent VTE, and the primary safety outcome was major bleeding. The incidence rates of thrombotic and bleeding outcomes by anticoagulation management strategies were descriptive, and were pooled using random effects model and expressed as events per 100 patient-months with associated 95 % confidence intervals (CI)., Results: We included 19 observational cohort studies (N = 1728 patients) in the systematic review, with 10 included in the meta-analysis (N = 707 patients). Approximately 90 % of patients had hematological malignancies, with low-molecular-weight heparin being the main anticoagulant. The rates of recurrent VTE and bleeding complications were high regardless of management strategies - recurrent VTE on full dose: 2.65/100 patient-months (95 % CI 1.62-4.32), modified dose: 3.51/100 patient-months (95 % CI 1.00-12.39); major bleeding on full dose: 4.45/100 patient-months (95 % CI 2.80-7.06), modified dose: 4.16/100 patient-months (95 % CI 2.24-7.74). There was serious risk of bias in all studies., Conclusions: Patients with cancer-associated thrombosis and thrombocytopenia have high risks of both recurrent VTE and major bleeding, but current literature is significantly limited to guide the best management., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: T-F. Wang reports research funding from Leo Pharma and advisory honoraria from Servier. M. Carrier reports grants from BMS, Leo Pharma and Pfizer, personal fees from BMS, Leo Pharma, Bayer, Pfizer, Servier and Sanofi. B.J. Carney reports personal fees from Sanofi. A. Delluc reports grants from Leo Pharma and Pfizer, personal fees from BMS, Leo Pharma, Pfizer, Servier., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: The collected evidence on thrombophilia guidelines is scarce and data about their impact on clinical decisions are unknown. We aimed to investigate the adherence to thrombophilia testing guidelines, its therapeutic impact in patients with guideline-adherent and non-adherent testing and identify the patients' clinical characteristics mostly associated with treatment decisions., Materials and Methods: We conducted a single-center cross-sectional study of patients referred for thrombophilia testing at the outpatient clinic of a tertiary hospital between 01/2010-10/2020. We systematically evaluated the adherence of thrombophilia testing to internal guidelines and the influence of test results on anticoagulation therapy. Using multivariable logistic regression, we evaluated the association between clinical characteristics and influence of thrombophilia tests on anticoagulation therapy in the entire cohort and by indication for referral., Results: Of 3686 included patients, mostly referred for venous thromboembolism (2407, 65 %) or arterial thrombosis (591, 16 %), 3550 patients (96 %) underwent thrombophilia testing. Indication for testing was according to guidelines in 1208 patients (33 %). Test results influenced treatment decisions in 56 of 1102 work-ups (5.1 %) that were adherent to guidelines, and in 237 of 2448 (9.7 %) non-adherent work-ups (absolute difference, 4.3 %; 95 % confidence interval, 2.9-6.3 %). Age < 50 years, female sex, absence of risk factors and co-morbidities, weakly provoked venous thromboembolism and referral indication other than venous thromboembolism were associated with influence on anticoagulation therapy., Conclusions: Adherence to guidelines for thrombophilia testing was poor and did not have an impact on treatment decisions. Refinement of selection criteria is needed to increase the therapeutic impact of thrombophilia testing., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: T.T. is an investigator of the CanVECTOR Network; the Network receives grant funding from the Canadian Institutes of Health Research (CDT-142654). The remaining authors declare no competing financial interests. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cancer is an increasingly recognized cause for ischemic stroke, with recent acknowledgement of cancer-related stroke as an emerging stroke subtype with unique pathophysiologic mechanisms. In addition, cancer-related stroke may differ from stroke in the general population as cancer patients may not receive guideline-recommended stroke care, and the occurrence of stroke may also preclude patients from receiving optimal cancer treatments. Due to the high degree of morbidity and mortality associated with both conditions, understanding the relationship between stroke and cancer is crucial. In this narrative review, we discuss the association between cancer and stroke, the unique pathophysiologic mechanisms underlying this phenomenon, treatment options including acute reperfusion therapies and secondary prevention strategies, compare outcomes between cancer-related stroke and stroke in the general population, and review new and emerging evidence in this field., 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 © 2022 Elsevier Ltd. All rights reserved.)

18 F-Fluorodeoxyglucose Positron Emission/Computed Tomography (FDG PET/CT) is a non-invasive whole-body imaging modality that has the potential for replacing multiple cancer screening tests by one. Previous studies showed that FDG PET/CT has an excellent sensitivity and negative predictive value for occult cancer screening in patients with unprovoked venous thromboembolism (VTE). In this patient population, FDG PET/CT is a reproducible imaging procedure with a kappa value estimated at 0.75. Although false positive results may lead to unnecessary investigations, it seems from recent evidence that invasive procedures triggered by a positive scan often resulted in cancer diagnosis. Trials assessing use of FDG PET/CT for occult cancer screening in patients with VTE at high risk for occult cancer diagnosis are ongoing., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Post-thrombotic syndrome (PTS) is one of the most frequent complications of venous thromboembolism (VTE) leading to considerable morbidity and cost. Apart from appropriate anticoagulation, there is no drug or medical intervention that helps to prevent PTS. We conducted a multicenter randomized controlled trial to determine whether rosuvastatin can prevent PTS., Methods: 312 patients receiving standard anticoagulation for a newly diagnosed VTE were randomly allocated to adjuvant rosuvastatin 20 mg once daily for 180 days (n = 155) or no rosuvastatin (n = 157). At the last study visit (Day 180 ± 21), an independent observer who was blinded to study treatment performed a PTS assessment using the Villalta scale. The primary clinical outcome of the trial was mean Villalta score at Day 180. We also explored the presence of PTS as defined by Villalta score > 4 at Day 180. Patients mean age was 46.7 ± 10.8 years, 55.8% were female., Results: At Day 180, the Villalta score was 3.5 ± 0.3 in the rosuvastatin arm vs. 3.3 ± 0.3 in the control arm (p = 0.59), and presence of PTS (Villalta >4) was 29.7% in the rosuvastatin arm vs. 25.5% in the control arm (p = 0.41). Secondary analyses showed no difference between trial arms for presence of severe PTS at Day 180 (2.0% vs. 2.7%, p = 1) and for changes in Villalta score between baseline and Day 180 (-3.7 ± 4.4 vs. -4.0 ± 5.0, p = 0.59)., Conclusion: This randomized controlled pilot trial did not demonstrate efficacy of rosuvastatin to reduce Villalta score. Further studies with longer duration of exposure to rosuvastatin are needed., Trial Registration: ClinicalTrials.gov, number NCT02679664., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Major bleeding is the most serious complication of oral anticoagulants (OACs). While consensus criteria to define major bleeding have been established by the International Society for Thrombosis and Haemostasis (ISTH), Bleeding Academic Research Consortium (BARC) and Thrombolysis in Myocardial Infarction (TIMI), significant variability exists across these definitions. We sought to evaluate the agreement of cases identified by the three definitions and to assess their effect on mortality and OAC resumption., Methods: We used a dataset of individuals ≥66 years in Ontario, Canada presenting with OAC-related bleeding from 2010 to 2015. For case agreement, we calculated Cohen's κ between the three major bleeding definitions. We used multivariate regression to determine differences in mortality and OAC resumption among ISTH, BARC and TIMI-defined major bleeds., Results: Among 2002 cases of OAC-related bleeding, agreement in case identification between ISTH and BARC was substantial (Cohen's κ = 0.69); however, agreement between TIMI and other definitions were poor. Using 30-day mortality of clinically relevant non-major bleeds as comparator, ISTH-, BARC- and TIMI-defined major bleeds conferred 3.3-, 3.2- and 5.9-fold increased risk. Among survivors, 50% with ISTH- and BARC-defined major bleeds resumed OACs at 180 days, compared to 31% of TIMI-associated cases., Conclusion: Major bleeds identified by ISTH and BARC criteria showed good agreement and similar prognostic utility, whereas TIMI criteria identified patients at greater clinical risk. Our results highlight the need to revise major bleeding definitions based on criteria that are independently predictive of clinically relevant morbidity and mortality to more effectively reflect the risk associated with major bleeding and appropriately influence anticoagulant therapy decisions., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Patients with cancer have increased risks of venous and arterial thromboembolism and/or atrial fibrillation, for which anticoagulation is commonly used. For these indications, three main types of anticoagulants are recommended or used: low-molecular-weight heparin (LMWH), direct oral anticoagulants (DOACs), and vitamin K antagonists (VKAs), all have different advantages and disadvantages. Drug-drug interactions (DDIs) with anticoagulation are often cautioned against by major guidelines, but evidence remains scarce regarding the best management approach for specific drug combinations, particularly with DOACs. Significant DDIs might affect the efficacy and safety of anticoagulants and/or anticancer therapies as well as other interfering medications, and more studies are needed. This paper will review the available evidence and guidelines on DDIs with anticoagulants, focusing on the cancer population whenever possible, and propose directions for future research., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Venous thromboembolism (VTE) is a leading cause of mortality in patients with cancer and is associated with significant morbidity and healthcare expenditure. The risk of VTE is increased following the insertion of a central venous catheter (CVC) for chemotherapy delivery and supportive care. The risks and benefits of primary thromboprophylaxis in patients with cancer and CVC are unclear., Objective: We sought to assess the rates of VTE and bleeding complications and to determine the efficacy and safety of primary thromboprophylaxis in adult patients with cancer and a CVC., Methods: A systematic search of MEDLINE, EMBASE, and all EBM was conducted. Randomized controlled trials (RCTs) of adult patients with cancer and a CVC receiving primary thromboprophylaxis compared to observation/placebo were included. The primary efficacy and safety outcomes were total VTE and major bleeding episodes, respectively., Results: A total of 12 RCTs (3545 patients) were included in the analysis. The total rates of VTE were significantly lower in patients receiving thromboprophylaxis compared to those not receiving primary prevention (7.6% vs. 13%; Odds Ratio (OR) 0.51, 95% CI 0.32-0.82, p < 0.01). The rates of major bleeding complications were not higher in patients receiving thromboprophylaxis (0.9% vs. 0.6%; OR 1.12, 95% CI 0.29-4.40, p = 0.87)., Conclusions: Primary thromboprophylaxis significantly reduced the risk of VTE without increasing the risk of major bleeding complications in patients with cancer and CVC. Future studies are needed to confirm these findings., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Postoperative venous thromboembolism (VTE) is a significant source of morbidity and mortality in cancer patients undergoing major abdominopelvic surgery. Many guidelines recommend the use of extended duration postoperative low molecular weight heparin (LMWH) thromboprophylaxis, although the evidence for its overall safety and efficacy is unclear., Aims: We sought to assess the 30-day postoperative rates of VTE and bleeding complications following major abdominopelvic cancer surgery and to explore the potential risks and benefits of extended duration thromboprophylaxis with LMWH in such setting., Methods: A systematic search of the literature was conducted. Observational studies and RCTs of adult patients that underwent abdominopelvic cancer surgery were included. Pooled proportions for the outcome measures and pooled relative risks for the extended duration thromboprophylaxis analyses were generated., Results: A total of 68 studies (1,631,118 patients) were included in the analysis. The 30-day postoperative rate of VTE was 1.7% (95%CI: 1.5 to 1.9, I 2  = 98%). The postoperative rate of clinically-relevant bleeding complications was 3.5% (95%CI: 1.6 to 6.1, I 2  = 99%). Extended duration thromboprophylaxis was associated with a significant reduction in the incidence of clinical VTE (1.0% vs 2.1%; Risk ratio (RR) 0.48, 95%CI: 0.31 to 0.74; I 2  = 0), without a significant increase in clinically-relevant bleeding (4.0% vs. 4.9%; RR 1.0, 95%CI: 0.66 to 1.5, I 2  = 0)., Conclusions: The overall risk of symptomatic VTE within 30 days of surgery was relatively low. Extended LMWH thromboprophylaxis following major abdominopelvic cancer surgery was associated with a reduced incidence of clinical VTE without an increase in clinically-relevant bleeding., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Exogenous hormone therapies, such as combined oral contraceptives (COC) and hormone replacement therapy (HRT), cause blood hypercoagulability and are a risk factor for venous thromboembolism (VTE). There is controversy on how strong this "provoking" risk factor is, and how other risk factors may synergise VTE risk. We aim to review the latest literature on the risk of initial and recurrent VTE with COC and HRT use to provide guidance for decision-making about duration of anticoagulation, and guide future research efforts., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Oral anticoagulant (OAC) intervention trials have typically included clinical event outcomes. However, there is no standard list of outcomes to be used in OAC research. This study aimed to describe and classify the outcomes used in recent prospective clinical studies involving OACs., Materials and Methods: We searched MEDLINE, EMBASE, and CINAHL databases from January 2009 to July 2019 for prospective studies with an intervention or control group that included one or more oral anticoagulants. We abstracted details about each included study and the outcomes used from the study report and its accompanying protocol. Using the Core Outcome Measures in Effectiveness Trials (COMET) Initiative recommendations, we categorised each outcome into one of five domains (mortality/survival, physiological/clinical, life impact, resource use, and adverse events). Our primary outcome was the prevalence of use of an outcome domain across studies., Results: We included 70 prospective studies, including 52 randomized controlled trials and 18 prospective cohort studies. A total of 121 different outcomes were reported. The COMET domains were represented in the 70 studies as follows: mortality (63/70, 90.0%); physiological/clinical domain (70/70, 100%), life impact domain (43/70, 61.4%), resource use domain (26/70, 37.1%), and adverse events domain (55/70, 78.6%)., Conclusion: Outcome reporting in prospective studies of OACs more frequently concentrates on mortality, physiological/clinical domains, and adverse events compared to life impact and resource utilization domains, the latter uncommonly used. A priority for future research includes developing a core outcome set (COS) for OAC research that represents all domains., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Venous thromboembolism (VTE) is a common complication after intracranial hemorrhage (ICH); the incidence has been reported to vary between 18% to 50% for deep vein thrombosis and between 0.5% to 5% for pulmonary embolism (PE). According to current clinical practice guidelines, patients with acute VTE should receive anticoagulant treatment for at least 3 months in the absence of contraindications. Anticoagulant treatment reduces mortality, prevents early recurrences and improves long-term outcome in patients with acute VTE. However, recent ICH is an absolute contraindication for anticoagulant treatment due to the potential increased risk of hematoma expansion or recurrent ICH. Hematoma expansion occurs in approximately a third of patients within 24 h following the diagnosis of a spontaneous ICH. The risk for recurrent ICH depends on patients' features as well as on the feature of index ICH. Limited evidence is available on the risks of therapeutic anticoagulation started shortly after ICH. Expert consensus around the introduction of therapeutic anticoagulation suggests delaying therapeutic anticoagulation for at least 2 weeks after spontaneous ICH, until the risk re-bleeding becomes acceptable. Vena cava filters should be inserted to reduce the risk for (non) fatal PE until therapeutic anticoagulation can be started; antithrombotic prophylaxis should be started as soon as possible to avoid recurrent VTE after vena cava filter insertion. For patients presenting PE with hemodynamic compromise, percutaneous embolectomy should be considered. Most patients will be able to receive anticoagulant treatment within 4 weeks following spontaneous ICH; direct oral anticoagulants are probably the treatment of choice for those ICH patients tolerating anticoagulant treatment., (Copyright © 2021. Published by Elsevier Ltd.)

Introduction: Bariatric surgery patients experience an increased risk of venous thromboembolism (VTE), however, the optimal dose of low-molecular-weight heparin for VTE prophylaxis remains uncertain. Currently, St. Joseph's Healthcare Hamilton utilizes a weight-adjusted tinzaparin dosage (50 to 75 units/kg rounded to nearest pre-filled syringe) for postoperative VTE prophylaxis., Objectives: This study analyzed the safety of weight-adjusted tinzaparin for VTE prophylaxis in bariatric surgery patients weighing ≥160 kg., Methods: This was a retrospective study involving patients weighing ≥160 kg that underwent bariatric surgery from September 2015 to September 2019. Patients received a single dose of weight-adjusted subcutaneous unfractionated heparin (UFH) [5000 or 7500 IU] immediately prior to surgery, subcutaneous UFH [5000 IU, 7500 IU, or unspecified] immediately postoperatively, and either 10,000 or 14,000 IU of tinzaparin, beginning on the day after surgery, for 10 days. Intra-operative sequential compression devices could be used at the attending surgeon's discretion. Occurrence of VTE and major bleeding within 30 days of surgery were assessed., Results: A total of 389 patients were included for analysis, all patients received in-hospital follow-up while 349 patients had also 30-day follow-up. For the primary safety and efficacy analysis of in-hospital events, VTE and major bleeding rates were 0.26% [95% CI 0.01%-1.44%] (1/389) and 0.77% [95% CI 0.21%-2.24%] (3/389) respectively. For patients with 30-day follow-up VTE and major bleeding rates were 0.57% [95% CI 0.1%-2.07%] (2/349) and 1.43% [95% CI 0.61%-3.3%] (5/349) respectively., Conclusions: Weight-adjusted tinzaparin was associated with a low risk of bleeding and VTE events, supporting its use for VTE prophylaxis for patients weighing ≥160 kg., (Copyright © 2020. Published by Elsevier Ltd.)

Guidelines suggest broad use of pharmacologic prophylaxis to prevent venous thromboembolism (VTE) in hospitalized medical patients, however little 'real-world' data exists to support this. Our goal was to describe the use of thromboprophylaxis among general medical and cancer patients admitted to hospital, compare VTE and bleeding outcomes according to use of thromboprophylaxis, and to determine what variables influence prescribing patterns and outcomes. Patients admitted to the general medical and oncology services at The Ottawa Hospital between 2010 and 2015 were retrospectively reviewed and classified according to whether they received initial, delayed, or no pharmacologic thromboprophylaxis during their first hospitalization. Patients with an alternate indication for anticoagulation or those admitted with a bleeding event were excluded from analysis. The primary efficacy outcome was any symptomatic VTE during index hospitalization or within 90 days of discharge, and the primary safety outcome was clinically relevant bleeding during the index hospitalization. 17,262 patients were included in our final analysis. General medical patients selected to receive no, initial, or delayed thromboprophylaxis had 0.4%, 0.7%, and 2.4% rates of VTE; and 0.2%, 0.7%, and 1.5% rates of clinically relevant bleeding complications, respectively. Cancer patients had significantly higher rates of VTE: 3.3%, 3.9%, and 5.0%; and 0.9%, 0.7%, and 3.0% rates of clinically relevant bleeding among those selected to receive no, initial, or delayed thromboprophylaxis, respectively. Overall, our study suggests that broad use of pharmacologic thromboprophylaxis may be unnecessary in select low-risk general medical patients and may be less effective in cancer patients in whom new studies are indicated., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Cancer therapy and progress in quality of imaging technologies for cancer surveillance and staging are in cause for the increase incidence of smaller incidental pulmonary embolism (PE). The clinical significance of incidental subsegmental pulmonary embolism (SSPE) is hard to define, balancing between possible false positive result, hypercoagulability signal, and truly venous thromboembolism (VTE) event. Evidence for optimal management of such findings are largely extrapolated from symptomatic SSPE in non-cancer patients and from symptomatic, more proximal PE in cancer patients. Current practice guidelines vary but some suggest withholding anticoagulation in selected patients. However, most SSPEs, incidental or not, should be treated as any other cancer-associated PE due to likely similar prognosis. Choice and duration of anticoagulation are extended from existing knowledge on more proximal PE., (Copyright © 2020. Published by Elsevier Ltd.)

Introduction: Risk assessment models are used to stratify cancer patients according to their underlying risk of VTE. The CATS score has been shown to enhance VTE risk stratification as compared to the modified Khorana score by incorporating d-dimer and soluble p-selectin measurements. Our aim was to evaluate the performance of the CATS score with respect to VTE risk stratification., Materials and Methods: Analysis of a subset of the AVERT trial population for whom biomarker data was available. All patients included in the AVERT trial were at increased risk of VTE based on a modified Khorana score of ≥2. Patients were stratified according to the modified Khorana score and CATS score. Kaplan-Meier analysis was used to calculate the 6-month cumulative probabilities of VTE., Results: A total of 466 patients were included in the analysis, 229 and 237 patients in the placebo and apixaban arms, respectively. The 6-month cumulative probability of VTE among patients with a modified Khorana score ≥ 3 was 13% [95% CI 7 to 23], whereas it was 20% [95% CI 11 to 35] for patients with a CATS score ≥ 4. The absolute risk reduction achieved with apixaban VTE prophylaxis among patients with modified Khorana ≥2, modified Khorana ≥3 and CATS ≥4 was -5.9% [-10.9 to -0.8], -5.8% [-16.0 to 4.5] and -10.1% [-22.9 to 2.6], respectively. Apixaban VTE prophylaxis among patients with increasing modified Khorana or CATS scores was not associated with an increased risk of bleeding events., Conclusions: The use of a CATS score of ≥4 to identify ambulatory cancer patients at very high risk of VTE could enhance the benefit/risk ratio achieved with apixaban VTE prophylaxis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Title: Comparison of the Wells score and the revised Geneva score as a tool to predict pulmonary embolism in outpatients over 65 years of age., Introduction: The incidence and mortality of pulmonary embolism (PE) is high in the elderly. The Wells score (SW) and the revised Geneva score (RGS) have been validated in patient populations with a large age range. The aim of this study was to compare the predictive accuracy of these two scores in diagnosis of PE in patients over 65 years of age., Method: A prospective multicentre study (nine French and three Belgian centres) was conducted at the same time as the PERCEPIC study. A total of 1757 patients admitted with suspected PE were included and divided into two groups according to age (≥65 years or <65 years). The pre-test probability of PE was assessed prospectively for the RGS. The SW was calculated retrospectively. The predictive accuracy of the two scores was compared by the area under the curve (AUC) of the ROC curves., Results: The overall prevalence of PE was 11.3%. The prevalence among patients aged ≥65 in the low, moderate and high pre-test probability groups, evaluated using the WS and was respectively 13.5% (CI 95%: CI 9.9-17.3), 28.2% (CI 22.1-34.3), 50% (CI 26-74) and 8.1% (CI 3.2-12.9), 22.3% (CI 18.2-26.3), 43.7% (CI 25.6-61.9) using the RGS. The AUC for the WS and RGS for patients aged ≥65 was 0.632 (CI 0.574-0.691) and 0.610 (CI 0.555-0.666). The difference between the AUCs was not statistically significant (p = .441)., Conclusion: In the population for this study, the WS and RGS have the same PE diagnostic accuracy in patients over age 65. This result should be validated in a prospective study that directly compares these scores., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the value of biomarkers to prognosticate outcomes in patients with pulmonary embolism among studies of sound methodical quality., Methods: Ovid MEDLINE, Embase, CENTRAL, and non-indexed citations were searched from inception to March 2019. Biomarkers of interest included troponin I (TnI), troponin T (TnT), high-sensitive TnT (HS-TnT), brain natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP), heart fatty acid binding protein (H-FABP), and D-dimer (DD). Included studies utilized key features of the Reporting Recommendations for Tumour Marker Prognostic Studies (REMARK) checklist and satisfied requirements of the Quality in Prognosis Studies (QUIPS) tool. The primary outcome was 30-day all-cause mortality (ACM). Secondary outcomes included PE-related mortality, or complicated clinical course (CCC). Pooled relative risk ratios (RR) were calculated using inverse-variance-weighted random-effects method., Results: Seventeen studies were analyzed. TnT ≥ 0.1 ng/mL and HS-TnT ≥ 14 pg/mL were associated with an increased 30-day ACM with RRs of 6.24 (95% CI, 1.86-20.96, I 2  = 35%) and 6.81 (95% CI, 2.46-18.88, I 2  = 0%), respectively. In the short-term (≤30 days): (1) TnI can prognosticate PE-related mortality; (2) both TnT and HS-TnT can prognosticate a CCC; (3) H-FABP can prognosticate a CCC; and (4) NT-proBNP can prognosticate a CCC. In the long-term (>30 days): (1) HS-TnT can prognosticate ACM; and (2) NT-proBNP can prognosticate ACM and PE-related mortality., Conclusions: Several methodically sound studies allow for data pooling, and suggest that TnT, HS-TnT, TnI, NT-proBNP and H-FABP have prognostic value in patients with PE but confidence intervals are wide and relatively few patients constitute the analyses. The value of such markers on influencing clinical management remains to be determined., Systematic Review Registration: PROSPERO CRD42019129889., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Studies evaluating the use of activated prothrombin complex concentrates (aPCCs) for DOAC-associated bleeding are sparse., Materials and Methods: We conducted a retrospective study of patients receiving aPCC for DOAC-associated bleeding or for pre-operative optimization of hemostasis prior to urgent surgery. The primary efficacy outcome was hemostatic efficacy, the primary safety outcome was the 30-day thromboembolic complication rate., Results: Eighty-two patients were included in the analysis; 14 patients on dabigatran, 39 patients on rivaroxaban and 29 patients on apixaban. Fifty-four patients received aPCC for major bleeding and 28 patients prior to urgent surgery. Mean aPCC dosing was 2974 IU (SD ± 857 IU). Hemostasis was deemed effective by ISTH criteria in 50% of cases and "Good" or "Moderate" by Sarode criteria in 45.2% and 14.3% of cases, respectively. Surgical hemostasis was rated as "Normal" in 84% of cases pre-operative administration. Median pre-aPCC INR was 1.6 (IQR 0.5) and median post-aPCC INR was 1.2 (IQR 0.2) (p < 0.00001). Median pre-aPCC aPTT was 36 s (IQR 12.8), median post-aPCC aPTT was 29 s (IQR 9.8) (p = 0.0001). The 30-day thromboembolic event rate was 6.1%., Conclusion: Further study is needed to characterize the hemostatic effects and thromboembolic risk of aPCC among patients with DOAC-associated bleeding or for attempted normalization of hemostasis prior to urgent surgery., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: The therapeutic effects of low molecular weight heparins (LMWH) may extend past thrombosis prevention, with preclinical evidence demonstrating anti-metastatic properties. Clinical evidence on the topic, however, remains controversial. A systematic review of preclinical evidence may help elucidate reasons for this contradictory evidence. The objective of our systematic review is to assess the anti-metastatic properties of LMWHs in solid tumour animal models., Methods: MEDLINE, Embase, Web of Science and PubMed were searched from inception to May 12th, 2020. All articles were screened independently and in duplicate. Studies that compared LMWH to a placebo or no treatment arm in solid tumour animal models were included. The primary outcome was the burden of metastasis. Secondary outcomes included primary tumour growth and mortality. The risk of bias was assessed in duplicate using a modified Cochrane Risk of Bias tool., Results: Forty-two studies were included in the review. Administration of a LMWH was associated with a significant decrease in the burden of metastasis (SMD -2.18; 95% CI -2.66 to -1.70). Additionally, the administration of a LMWH was also associated with a significant reduction in primary tumour growth (SMD -1.95; 95% CI -2.56 to -1.34) and risk of death (RR 0.39; 95% CI 0.16-0.97). All included studies were deemed to be at an unclear risk of bias for at least one methodological criterion., Conclusions: Our results demonstrate that LMWH can effectively reduce metastatic burden and reduce tumour growth in preclinical animal models of solid tumour malignancies. Reasons for the contradiction with clinical evidence require further exploration., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Venous thromboembolism (VTE) may be the first manifestation of cancer. We aimed at evaluating the performance of 18 F-Fluorodesoxyglucose Positron-Emission Tomography/Computed Tomography (FDG PET/CT) for occult cancer screening in patients with unprovoked VTE., Methods: This was a pre-specified analysis of a systematic review and individual patient data meta-analysis including prospective studies assessing cancer screening in patients with unprovoked VTE. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FDG PET/CT were calculated based on cancer diagnosis during a 1-year follow-up period., Results: Four studies were identified as using FDG PET/CT as part of their extensive screening strategy. Out of the 332 patients who underwent FDG PET/CT, the scan was interpreted as positive in 67 (20.2%), as equivocal in 27 (8.1%), and as negative in 238 (71.7%). Seventeen (5.1%) patients were diagnosed with cancer at inclusion or during the 12-month follow up period. All cancers were diagnosed at initial screening. Pooled sensitivity, specificity, NPV, and PPV were 87.3% (95% CI, 55.3 to 97.4), 70.2% (95% CI, 48.2 to 85.6), 98.9% (95% CI, 94.3 to 99.7), and 17.9% (95% CI, 8.5 to 33.6), respectively., Conclusion: FDG PET/CT appears to have satisfactory accuracy indices for cancer diagnosis in patients with unprovoked VTE. In particular, it exhibits a very high negative predictive value and could be used to rule out the presence of an underlying occult malignancy in this setting., Competing Interests: Declaration of competing interest Dr. Le Gal holds an Early Researcher Award from the Province of Ontario; a Heart and Stroke Foundation of Canada (HSFC) Ontario Mid-Career Investigator Award; and the Chair on Diagnosis of Venous Thromboembolism from the Department of Medicine at the University of Ottawa. Dr. Salaun reports a grant from the French Health Ministry (PHRC Cancer 2008) during the conduct of the MVTEP study. Authors not named here have disclosed no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Venous thromboembolism (VTE) is a life-threatening, yet potentially preventable, complication of inflammatory bowel disease (IBD). The incidence of VTE in IBD is roughly three-fold greater than in the general population, and results in a 2-fold increased risk of mortality. The absolute risk is highest during hospitalization and has led to consensus guidelines recommending thromboprophylaxis for all admitted patients with IBD in the absence of contraindications. Emerging evidence suggests that the risk of VTE is likely to remain high early after hospital discharge. Despite this, it remains unclear if thromboprophylaxis should be continued after hospitalization. Therefore, this review will synthesize the available literature pertaining to the post-discharge setting with a focus on the incidence of VTE, associated risk factors, and the potential role for extended thromboprophylaxis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Arterial thrombosis and venous thromboembolism (VTE) are traditionally considered two different entities. However, patients with unprovoked VTE are at higher risk of developing subclinical and overt atherosclerosis compared to healthy controls challenging these distinctions. Obesity may explain the association between arterial and venous disease: overweight/obese patients are prone to stasis in lower limbs veins, chronic inflammation, dyslipidemia, hypertension, and diabetes mellitus; all of which result in a hypercoagulability, VTE, and atherosclerosis. Novel therapeutic approaches combining and re-purposing traditional arterial therapies (antiplatelets and statins) and venous thrombosis therapies (anticoagulants) are emerging for the management of patients with vascular disease., (Copyright © 2020 Elsevier Ltd. All rights reserved.)