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Patients with multiple myeloma (MM) were among the groups impacted more severely by the COVID-19 pandemic, with higher rates of severe disease and COVID-19-related mortality. MM and COVID-19, plus post-acute sequelae of SARS-CoV-2 infection, are associated with endothelial dysfunction and injury, with overlapping inflammatory pathways and coagulopathies. Existing treatment options for MM, notably high-dose therapy with autologous stem cell transplantation and novel chimeric antigen receptor (CAR) T-cell therapies and bispecific T-cell engaging antibodies, are also associated with endothelial cell injury and mechanism-related toxicities. These pathologies include cytokine release syndrome (CRS) and neurotoxicity that may be exacerbated by underlying endotheliopathies. In the context of these overlapping risks, prophylaxis and treatment approaches mitigating the inflammatory and pro-coagulant effects of endothelial injury are important considerations for patient management, including cytokine receptor antagonists, thromboprophylaxis with low-molecular-weight heparin and direct oral anticoagulants, and direct endothelial protection with defibrotide in the appropriate clinical settings., Competing Interests: Declaration of competing interest C.C.M.: Advisory boards for AbbVie, Bristol Myers Squibb, GSK, Janssen, Karyopharm, Sanofi, and Takeda; consultancy for AbbVie, Janssen, Karyopharm, and Sanofi. E.R.: None. E.C.: None. F.C.: None. M.H.K.: Grants to institution for clinical trials from Bristol Myers Squibb/Celgene, Janssen, AbbVie, Arcellx/Kite, Roche and Poseida Therapeutics. R.M.B.: None. J.M.C.: Consulting and scientific advisory boards for Abbott, Anthos, Bristol Myers Squibb, Roche, Sanofi, and Werfen; research funding to the institution from CSL Behring. M.I.: None. L.-J.W.: None. A.P.R.: None. M.D.-R.: Speaker fees from Jazz Pharmaceuticals and research funding to institution from Novartis Spain, CSL Behring, and Sysmex Europe GmbH. J.M.M.: Research support from Pfizer, Gilead, Novartis, Bristol Myers Squibb, Amgen, and Roche, and advisory committees for Rocket Pharma, Jazz Pharma, Novartis, Gilead, and Sandoz. C.C.-S.: Consultancy with Sanofi, membership of the board of directors, speakers bureau, or advisory committee for ADC Therapeutics SA, Bristol Myers Squibb, Celgene, Karyopharm, Roche, and Sanofi; research funding from ADC Therapeutics SA, Roche, and Sanofi; honoraria from ADC Therapeutics SA, AstraZeneca, Bristol Myers Squibb, Incyte, Janssen Oncology, and Takeda. P.G.R.: Grants to institution for clinical trials from Bristol Myers Squibb / Celgene, Karyopharm, and Oncopeptides; advisory committees for Bristol Myers Squibb / Celgene, GSK, Karyopharm, Oncopeptides, Adaptive Biotechnologies, and Sanofi., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Based on emerging evidence from the COVID-19 pandemic, the International Society on Thrombosis and Haemostasis (ISTH) guidelines for antithrombotic treatment in COVID-19 were published in 2022. Since then, at least 16 new randomized controlled trials have contributed additional evidence, which necessitated a modification of most of the previous recommendations. We used again the American College of Cardiology Foundation/American Heart Association methodology for assessment of level of evidence (LOE) and class of recommendation (COR). Five recommendations had the LOE upgraded to A and 2 new recommendations on antithrombotic treatment for patients with COVID-19 were added. Furthermore, a section was added to answer questions about COVID-19 vaccination and vaccine-induced immune thrombotic thrombocytopenia (VITT), for which studies have provided some evidence. We only included recommendations with LOE A or B. Panelists agreed on 19 recommendations, 4 for nonhospitalized, 5 for noncritically ill hospitalized, 3 for critically ill hospitalized, and 2 for postdischarge patients, as well as 5 for vaccination and VITT. A strong recommendation (COR 1) was given for (a) use of prophylactic dose of low-molecular-weight heparin or unfractionated heparin in noncritically ill patients hospitalized for COVID-19, (b) for select patients in this group, use of therapeutic-dose low-molecular-weight heparin/unfractionated heparin in preference to prophylactic dose, and (c) for use of antiplatelet factor 4 enzyme immunoassays for diagnosing VITT. A strong recommendation was given against (COR 3) the addition of an antiplatelet agent in hospitalized, noncritically ill patients. These international guidelines provide recommendations for countries with diverse healthcare resources and COVID-19 vaccine availability., Competing Interests: Declaration of competing interests S.S. has received a research grant from Octapharma; served on data safety monitoring boards for Alexion, Bayer, Boehringer-Ingelheim, and Sanofi; served on event adjudication for Daiichi Sankyo; and served on an advisory board for Servier. D.M.A. received research grants from Rigel Pharmaceuticals and the Public Health Agency of Canada and is a consultant for Amgen, Paradigm, Sobi, Alpine, Novartis, and Argenx. C.A.B. has received a research grant from Amgen, honoraria from BMS-Pfizer, Janssen, and Sanofi, and served on the advisory board for Novartis. L.B. currently owns a stock portfolio with Johnson & Johnson and Pfizer. J.M.C. has received a research grant from CSL Behring and has served on scientific advisory boards for Abbott, Anthos, Bristol Myers Squibb, Pfizer, and Werfen. A.F. has received honoraria from Kedrion and Rovi and served on an advisory board for Sanofi. S.K. has received research grants from Bayer and is a consultant for Inari and Janssen. J.H.L. has served on a data safety monitoring board with Merck, a research study steering committee with Octapharma, and the advisory board for Werfen. S.M. has received research grants from Bayer, Abbvie, Hemab, Viatris, and Sanofi and honoraria from AstraZeneca, Norgine, and Alveron. I.N. has received research grants from Paradigm Pharmaceuticals, Janssen/Johnson & Johnson, UCB Biopharma, AstraZeneca, and the Public Health Agency of Canada and is a consultant for Paradigm Pharmaceuticals, Janssen/Johnson & Johnson, UCB Biopharma, and AstraZeneca. E.R. has received research grants from Bayer, Pfizer, and Novartis and honoraria from Sanofi, Bayer, Ache, Daiichi Sankyo, and Pfizer. C.M.S. served on an advisory board for Norgine Pharma. M.S. has received research grants from Pfizer, Amgen, and Sanofi; received honoraria from Pfizer, Octapharma, Amgen, and Novartis; and served on advisory boards for Amgen and Novartis. A.C.S. has received a research grant from AstraZeneca and honoraria from Janssen, Regeneron, and AstraZeneca. J.T. received honoraria from Bristol Myers Squibb, Pfizer, and Daiichi Sankyo. R.Z. has received research grants from the Canadian Institute of Health Research, LifeArc, Nation Institute of Health, Research Manitoba, CancerCare Manitoba Foundation, Peter Munk Cardiac Centre, Thistledown Foundation, and Manitoba Medical Services Foundation. The remaining authors have no conflicts of interest to declare. S.S. has been primary author and coauthor on review articles on COVID-19. D.M.A. has been coauthor and senior author on articles on diagnosis and treatment of VITT. C.A.B. has been primary author and co-author on articles on heparins and antiplatelet agents for treatment of COVID-19. J.M.C. has been primary author and coauthor on articles on antiplatelet agents, apixaban, and heparin for treatment of COVID-19. A.F. has been coauthor on review articles on treatment of COVID-19, including with heparin. T.I. has been primary author and coauthor on articles on coagulopathy in COVID-19 and in VITT. S.K. has been coauthor on articles on heparin and antiplatelet agents for treatment of COVID-19. J.H.L. has been primary author and coauthor on articles on coagulopathy in COVID-19 and in VITT and on heparin for treatment of COVID-19. S.M. has been coauthor on articles on heparin and oral anticoagulants for the treatment of COVID-19. I.N. has been primary author, senior author, and coauthor on articles on coagulopathy and laboratory diagnosis in VITT and COVID-19. C.M.S. has been coauthor on articles on coagulopathy in COVID-19. M.S. has been primary author on articles on heparin for treatment of COVID-19. A.C.S. has been primary author and senior author on articles on heparin and coauthor on articles on rivaroxaban for treatment of COVID-19. J.T. has been primary author and coauthor on articles on coagulopathy in COVID-19. R.Z. has been primary author and coauthor on articles on heparin and antiplatelet agents, respectively, for treatment of COVID-19. The remaining authors have no intellectual conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cancer-associated venous thromboembolism (CAT) has detrimental impact on patients' clinical outcomes and quality of life. Data on CAT education, communication, and awareness among the general cancer population are scanty., Methods: We present the preliminary results of an ongoing patient-centered survey including 27 items covering major spheres of CAT. The survey, available in 14 languages, was promoted and disseminated online through social networks, email newsletters, websites, and media., Results: As of September 20, 2022, 749 participants from 27 countries completed the survey. Overall, 61.8% (n = 460) of responders were not aware of their risk of CAT. Among those who received information on CAT, 26.2% (n = 56) were informed only at the time of CAT diagnosis. Over two thirds (69.1%, n = 501) of participants received no education on signs and symptoms of venous thromboembolism (VTE); among those who were educated about the possible clinical manifestations, 58.9% (n = 119) were given instructions to seek consultation in case of VTE suspicion. Two hundred twenty-four respondents (30.9%) had a chance to discuss the potential use of primary thromboprophylaxis with health-care providers. Just over half (58.7%, n = 309) were unaware of the risks of bleeding associated with anticoagulation, despite being involved in anticoagulant-related discussions or exposed to anticoagulants. Most responders (85%, n = 612) valued receiving CAT education as highly relevant; however, 51.7% (n = 375) expressed concerns about insufficient time spent and clarity of education received., Conclusions: This ongoing survey involving cancer patients with diverse ethnic, cultural, and geographical backgrounds highlights important patient knowledge gaps. These findings warrant urgent interventions to improve education and awareness, and reduce CAT burden., (© 2022 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Antithrombotic agents reduce risk of thromboembolism in severely ill patients. Patients with coronavirus disease 2019 (COVID-19) may realize additional benefits from heparins. Optimal dosing and timing of these treatments and benefits of other antithrombotic agents remain unclear. In October 2021, ISTH assembled an international panel of content experts, patient representatives, and a methodologist to develop recommendations on anticoagulants and antiplatelet agents for patients with COVID-19 in different clinical settings. We used the American College of Cardiology Foundation/American Heart Association methodology to assess level of evidence (LOE) and class of recommendation (COR). Only recommendations with LOE A or B were included. Panelists agreed on 12 recommendations: three for non-hospitalized, five for non-critically ill hospitalized, three for critically ill hospitalized, and one for post-discharge patients. Two recommendations were based on high-quality evidence, the remainder on moderate-quality evidence. Among non-critically ill patients hospitalized for COVID-19, the panel gave a strong recommendation (a) for use of prophylactic dose of low molecular weight heparin or unfractionated heparin (LMWH/UFH) (COR 1); (b) for select patients in this group, use of therapeutic dose LMWH/UFH in preference to prophylactic dose (COR 1); but (c) against the addition of an antiplatelet agent (COR 3). Weak recommendations favored (a) sulodexide in non-hospitalized patients, (b) adding an antiplatelet agent to prophylactic LMWH/UFH in select critically ill, and (c) prophylactic rivaroxaban for select patients after discharge (all COR 2b). Recommendations in this guideline are based on high-/moderate-quality evidence available through March 2022. Focused updates will incorporate future evidence supporting changes to these recommendations., (© 2022 International Society on Thrombosis and Haemostasis.)

Background: Increased shear stress conferred upon the circulation by continuous-flow pumps is associated with hemocompatibility-related adverse events, principally bleeding within the gastrointestinal system, and linked to the degradation of high-molecular-weight multimers (HMWMs) of von Willebrand factor (vWF). We evaluated the structure and functional characteristics of vWF HMWMs in patients with the fully magnetically levitated centrifugal-flow HeartMate 3 (HM3) and the continuous axial-flow HeartMate II (HMII) pump. Findings were correlated with bleeding events., Methods: In a prospective, multicenter, comparative cohort study, 60 patients from the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 Continued Access Protocol (NCT02892955) with an HM3 pump were compared with 30 randomly selected HMII patients from the PREVENtion of HeartMate II Pump Thrombosis study (NCT02158403) biobank. The primary end point was the difference in the normalized vWF HMWM ratio (ratio of the HMWMs to the intermediate- and low-molecular-weight multimers, normalized to pooled plasma from healthy volunteers) between the HM3 and the HMII pump at 90 days after implantation. Assay tests for vWF activity, vWF antigen, vWF activity to antigen ratio, coagulation factor VIII activity, and ADAMTS13 activity were measured by using standard protocols. Differences in these markers were compared in the context of clinical characteristics and correlated with adjudicated bleeding events within the HM3 group., Results: Of 51 and 29 evaluable patients in the HM3 and HMII arms, respectively, those implanted with the HM3 pump exhibited greater preservation of the vWF HMWM ratio than those with the HMII pump at 90 days after implantation (54.1% vs 42.4%, p < 0.0001). Laboratory values for all vWF assays (antigen, activity, and coagulation factor VIII activity) remained within the normal functional range with no significant differences observed between the pumps at 90 days after implantation. At baseline, there was a decrease in the structural integrity of vWF HMWMs that correlated with increasing heart failure severity as measured by the Interagency Registry for Mechanically Assisted Circulatory Support profile. Multivariable modeling identified the HM3 pump as the only independent variable that determined post-implantation preservation of the structural integrity of vWF HMWMs., Conclusions: This prospective, multicenter comparative analysis study demonstrates that the fully magnetically levitated centrifugal-flow HM3 left ventricular assist device is associated with greater preservation of the structure of vWF HMWMs than the HMII mechanical bearing axial-flow pump., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The HeartMate 3 left ventricular assist system is engineered to avoid pump thrombosis, yet bleeding complications persist. We investigated the safety of low-intensity anti-coagulation in patients with the HeartMate 3., Methods: The Minimal AnticoaGulation EvaluatioNTo aUgment heMocompatibility (MAGENTUM 1) pilot study is a prospective, single-arm study of low-intensity warfarin anti-coagulation in patients implanted with the HeartMate 3 pump. After standard warfarin anti-coagulation (international normalized ratio [INR] 2.0 to 3.0) and aspirin for 6 weeks post-implant, patients were transitioned to a lower INR target range of 1.5 to 1.9. The primary end-point was a composite of survival free of pump thrombosis, disabling stroke (modified Rankin score [MRS] >3), or major bleeding (excluding peri-operative bleeding) with at least 6-month post-implant follow-up. Time in therapeutic range (TTR) was measured to assess anti-coagulation target efficacy using the Rosendaal method. A safety algorithm to monitor for signs of pump thrombosis was developed and implemented., Results: We enrolled 15 patients (mean age 57.3 ± 13.3 years), 13 men with advanced heart failure (67% with INTERMACS Profiles 2 or 3), irrespective of therapeutic goal of bridge-to-transplant or destination therapy. The primary end-point was met in 14 of 15 (93 ± 6%) patients; 1 patient developed recurrent gastrointestinal bleeding. The TTR during the reduced anti-coagulation phase (6 weeks to 6 months) was 75.3 ± 8.6%. No thrombotic events occurred., Conclusions: This pilot study suggests low-intensity anti-coagulation targeting an INR between 1.5 and 1.9 is achievable and safe with the HeartMate 3 cardiac pump in the short-term phase, 6-months post-implant. A large-scale trial is now warranted., (Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

We present a successful case of prevention of postoperative hemorrhage in a 70-year-old male on dabigatran, who developed an acute type A aortic dissection and subsequently underwent an emergent ascending aortic replacement., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)