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1
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Swan D, Turner R, Grove EL, Schulman S, Thachil J. Direct oral anticoagulant failure in patients with venous thromboembolism-why and what next? J Thromb Haemost 2025; 23:1774-1786. [PMID: 40199444 DOI: 10.1016/j.jtha.2025.03.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 03/19/2025] [Accepted: 03/24/2025] [Indexed: 04/10/2025]
Abstract
Management of recurrent thrombotic events in patients taking a direct oral anticoagulant can be challenging. In this review, we consider causes of so-called direct oral anticoagulant failure, from poor adherence, malabsorption, and drug interactions to the presence of undiagnosed antiphospholipid syndrome, cancer-associated thrombosis, severe thrombophilia, vasculitis, and other rare causes. We discuss the known or potential pathogenesis of venous thromboembolism recurrence in these situations and provide practical guidance to assist clinicians faced with these challenging cases.
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Affiliation(s)
- Dawn Swan
- Department of Haematology, Austin Health, Melbourne, Victoria, Australia.
| | - Robert Turner
- Department of Anaesthesia, Mercy Health, Melbourne, Victoria, Australia
| | - Erik Lerkevang Grove
- Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark
| | - Sam Schulman
- Department of Medicine, Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada; Department of Obstetrics and Gynecology and Perinatal Medicine, The First I.M. Sechenov Moscow State Medical University, Moscow, Russia
| | - Jecko Thachil
- MAHSC Professor, University of Manchester, Manchester, United Kingdom
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2
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Abdul-Rahman T, Roy P, Herrera-Calderón RE, Mueller-Gomez JL, Lisbona-Buzali M, Ulusan S, Awuah WA, Kuchma N, Mehta N, Agrawal A, Altibi A, Gupta R. Rivaroxaban to reduce the risk of major cardiovascular events in patients with chronic coronary artery disease or peripheral artery disease: a narrative review. Expert Opin Drug Saf 2025; 24:261-271. [PMID: 39919210 DOI: 10.1080/14740338.2025.2462652] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Revised: 10/26/2024] [Accepted: 12/19/2024] [Indexed: 02/09/2025]
Abstract
BACKGROUND Coronary Artery Disease (CAD) and Peripheral Artery Disease (PAD) are leading causes of morbidity and mortality. Despite medical advancements, patients remain at high risk for major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Traditional anticoagulation strategies have shown limited efficacy. Rivaroxaban, an oral factor Xa inhibitor, has emerged as a potential alternative. OBJECTIVES This review examines the role of rivaroxaban in reducing MACE and MALE in CAD and PAD patients, focusing on its pharmacology, efficacy, safety, and cost-effectiveness. METHODS A literature search was conducted in PubMed, Embase, and Scopus for studies on rivaroxaban's use in CAD and PAD. RESULTS The COMPASS trial demonstrated that rivaroxaban (2.5 mg twice daily) plus aspirin significantly reduced MACE and MALE but increased major bleeding. The COMPASS-LTOLE and VOYAGER PAD trials confirmed these findings. However, the COMMANDER HF trial found no benefit in heart failure patients without atrial fibrillation. Cost-effectiveness studies support rivaroxaban as a viable treatment strategy. CONCLUSION Rivaroxaban plus aspirin effectively reduces thrombotic events in high-risk CAD and PAD patients. Despite an increased bleeding risk, its benefits outweigh the risks in selected populations. Future studies should explore personalized treatment approaches and long-term outcomes.
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Affiliation(s)
| | - Poulami Roy
- Department of Medicine, North Bengal Medical College and Hospital, Siliguri, India
| | | | - Jann Ludwig Mueller-Gomez
- Center for Research in Health Sciences (CICSA), Faculty of Medicine, Anahuac University North Campus, Huixquilucan, Mexico
| | - Marcos Lisbona-Buzali
- Center for Research in Health Sciences (CICSA), Faculty of Medicine, Anahuac University North Campus, Huixquilucan, Mexico
| | - Sebahat Ulusan
- Faculty of Medicine, Suleyman Demirel University School of Medicine, Isparta, Turkey
| | | | | | - Nikhil Mehta
- Department of Cardiology, University of Missouri, Kansas, MO, USA
| | - Ankit Agrawal
- Department of Hospital Medicine, Cleveland Clinic, Cleveland, Ohio, USA
| | - Ahmed Altibi
- Department of Cardiovascular Medicine, Yale New Haven School of Medicine, New Haven, Connecticut, USA
| | - Rahul Gupta
- Department of Cardiovascular Medicine, Yale New Haven School of Medicine, New Haven, Connecticut, USA
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3
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Gochnauer B, Rodino A, Russell S, Bradley K. A Pilot Study Describing DOAC Level Results and Association With Clinical Outcomes. J Pharm Pract 2025; 38:149-154. [PMID: 38884944 DOI: 10.1177/08971900241262363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/18/2024]
Abstract
Purpose: Describe direct oral anticoagulant (DOAC) level ordering and interpretation practices in association with clinical outcomes at a vascular medicine clinic. Methods: This study was a retrospective, observational study including patients who had a DOAC level ordered and assessed while on DOAC therapy. The primary outcome was the proportion of DOAC levels within previously reported ranges. Secondary outcomes included thrombotic events, major and clinically relevant non-major bleeding events, and the proportion of DOAC level results which prompted a change in the therapeutic plan. Results: A total of 43 patients who had a DOAC level ordered while on DOAC therapy were included in the study. More patients were on apixaban than other DOACs, and the most common indication for anticoagulation was deep vein thrombosis (DVT) or pulmonary embolism (PE). The most common reasons for ordering DOAC levels included history of gastric bypass (n = 20) and drug-drug interactions (n = 8). Most patients on apixaban had in-range levels (n = 24) compared to out of-range levels (5 patients). More patients on rivaroxaban had a level out-of-range (n = 10) than in-range (n = 4). One patient had a DVT, resulting in hospitalization and change in DOAC therapy. Two patients had bleeding events, with 1 hospitalization and change in DOAC therapy. DOAC level results also prompted changes in therapeutic plans for 9 of the patients. Conclusion: DOAC level results did not always correlate with expected outcomes, and further research is warranted to clarify which clinical situations may benefit from ordering DOAC levels.
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Affiliation(s)
- Brittni Gochnauer
- Ambulatory Clinical Pharmacist, The University of Kansas Health System, Kansas City, KS, USA
| | - Anne Rodino
- Ambulatory Clinical Pharmacist Practitioner, UNC Health Rex, Raleigh, NC, USA
| | - Sarah Russell
- Ambulatory Clinical Pharmacist Practitioner, UNC Health Rex, Raleigh, NC, USA
| | - Kristin Bradley
- Ambulatory Clinical Pharmacist Practitioner, UNC Health Rex, Raleigh, NC, USA
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4
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Zwicker JI. Trousseau syndrome: management of refractory VTE. HEMATOLOGY. AMERICAN SOCIETY OF HEMATOLOGY. EDUCATION PROGRAM 2024; 2024:253-258. [PMID: 39644033 PMCID: PMC11665641 DOI: 10.1182/hematology.2024000552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/09/2024]
Abstract
Managing recurrent and refractory venous thromboembolism (VTE) in patients with cancer presents unique challenges. This review outlines the complexities and therapeutic strategies for recurrent VTE in cancer patients, which includes distinguishing thrombus acuity, differentiating between tumor and bland thrombi, and evaluating potential contributing factors including anticoagulant adherence, extrinsic tumor compression, drug interactions, and anticoagulant-specific considerations such as heparin-induced thrombocytopenia or antithrombin deficiency. Different anticoagulation strategies are discussed, including the administration of escalated-dose low molecular weight heparin (LMWH) as well as the indications and rationale for switching between direct oral anticoagulants or LMWH.
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Affiliation(s)
- Jeffrey I. Zwicker
- Department of Medicine, Hematology Service, Memorial Sloan Kettering Cancer Center, New York, NY; and Weill Cornell Medical College, New York, NY
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5
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Ebbitt LM, Kassel LE, McKenzie JJ, Palm NM, Smith AN. The pharmacist's role in optimizing medication management before, during, and after minimally invasive and bariatric surgery. Am J Health Syst Pharm 2024; 81:1124-1135. [PMID: 38662339 DOI: 10.1093/ajhp/zxae111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Indexed: 04/26/2024] Open
Abstract
PURPOSE Minimally invasive surgery (MIS) with integrated enhanced recovery pathways (ERPs) helps reduce length of stay and improve surgical outcomes. As these procedures have become more prevalent over time, pharmacists are in key positions to manage medications in the perioperative space to help optimize transitions of care and reduce safety events. Here we identify several clinical areas across phases of care for these procedures in which the knowledge and guidance of pharmacists, as members of the interprofessional team, are paramount. SUMMARY Perioperative pharmacy expertise is often required for MIS procedures in the areas of acid suppression, antithrombotic management, blood glucose control, drug formulation, immunosuppressant optimization, pain mitigation, and postoperative nausea and vomiting prevention and treatment. For each MIS procedure, pharmacists should identify and consider diet and anatomical changes as well as patient- and surgery-specific risk factors. Pharmacists can then utilize their knowledge of the pharmacokinetics and pharmacodynamics of individual medications along with evidence-based medicine to recommend selection of appropriate agents. CONCLUSION Pharmacist contributions to perioperative medication management for MIS procedures can improve care as surgical patients navigate transitions through the perioperative setting. Pharmacists can further incorporate medication expertise through development and implementation of institutional MIS protocols within the context of ERPs. As such, any pharmacist should feel empowered to aid in the care of surgical patients.
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Affiliation(s)
- Laura M Ebbitt
- Department of Pharmacy Services, University of Kentucky HealthCare, Lexington, KY, USA
| | - Lynn E Kassel
- Department of Pharmacy Practice, Drake University College of Pharmacy and Health Sciences, Des Moines, IA
- Department of Pharmacy Services, MercyOne West Des Moines Medical Center, West Des Moines, IA, USA
| | - Jeffrey J McKenzie
- Department of Pharmacy Services, Virginia Commonwealth University Health System, Richmond, VA, USA
| | - Nicole M Palm
- Department of Pharmacy, Cleveland Clinic, Cleveland, OH, USA
| | - April N Smith
- Department of Pharmacy Practice, Creighton University School of Pharmacy and Health Professions, Omaha, NE, USA
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6
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Van Cutsem E, Mahé I, Felip E, Agnelli G, Awada A, Cohen A, Falanga A, Mandala M, Peeters M, Tsoukalas N, Verhamme P, Ay C. Treating cancer-associated venous thromboembolism: A practical approach. Eur J Cancer 2024; 209:114263. [PMID: 39128187 DOI: 10.1016/j.ejca.2024.114263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 07/23/2024] [Accepted: 07/25/2024] [Indexed: 08/13/2024]
Abstract
Venous thromboembolism (VTE) is a common and potentially life-threatening complication in patients with cancer. Both cancer and its treatments increase the risk of developing VTE. Specific cancer types and individual patient comorbidities increase the risk of developing cancer-associated VTE, and the risk of bleeding is increased with anticoagulation therapies. The aims of this article are to summarize the latest evidence for treating cancer-associated VTE, discuss the practical considerations involved, and share best practices for VTE treatment in patients with cancer. The article pays particular attention to challenging contexts including patients with brain, lung, gastrointestinal, and genitourinary tumors and those with hematological malignancies. Furthermore, the article summarizes specific clinical scenarios that require additional treatment considerations, including extremes of body weight, nausea and gastrointestinal disturbances, compromised renal function, and anemia, and touches upon the relevance of drug-drug interactions. Historically, vitamin K antagonists and low-molecular-weight heparins (LMWHs) have been used as therapy for cancer-associated VTE. The development of direct oral anticoagulants has provided additional treatment options, which, in certain instances, offer advantages over LMWHs. There are numerous factors that need to be considered when treating cancer-associated VTE, and although various treatment guidelines are helpful, they do not reflect each unique scenario that may arise in clinical practice. This article provides a summary of the latest evidence and a practical approach for treating cancer-associated VTE.
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Affiliation(s)
- Eric Van Cutsem
- Department of Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Herestraat 49, Leuven 3000, Belgium.
| | - Isabelle Mahé
- Paris Cité University, Assistance-Publique-Hôpitaux de Paris (AP-HP), Service de Médecine Interne, Hôpital Louis-Mourier, 178 Rue des Renouillers, 92700 Colombes, France; Inserm UMR_S1140, Innovative Therapies in Haemostasis Paris, Paris, France
| | - Enriqueta Felip
- Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Centro Cellex, Carrer de Natzaret, 115-117, Barcelona 08035, Spain
| | - Giancarlo Agnelli
- Internal, Vascular and Emergency Medicine - Stroke Unit, University of Perugia, Piazza dell'Università, 1, 06123 Perugia, PG, Italy
| | - Ahmad Awada
- Institut Jules Bordet, Université Libre de Bruxelles, Mijlenmeersstraat 90, 1070 Bruxelles, Belgium
| | - Alexander Cohen
- Department of Haematology, Guy's and St Thomas' Hospitals, Kings College, London, UK
| | - Anna Falanga
- Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Piazza OMS, 1, 24127 Bergamo, BG, Italy; School of Medicine and Surgery, University of Milano Bicocca, Via Cadore 48, 20900 Monza, MB, Italy
| | - Mario Mandala
- Unit of Medical Oncology, University of Perugia, Santa Maria della Misericordia Hospital, Piazzale Giorgio Menghini, 3, 06129 Perugia, PG, Italy
| | - Marc Peeters
- Multidisciplinary Oncological Centre Antwerp (MOCA), Antwerp University Hospital, Drie Eikenstraat 655, Edegem 2650, Belgium; Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp and Antwerp University Hospital, Drie Eikenstraat 655, Edegem 2650, Belgium
| | - Nikolaos Tsoukalas
- Department of Oncology, 401 General Military Hospital of Athens, Athens, Greece
| | - Peter Verhamme
- Department of Cardiovascular Diseases, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium
| | - Cihan Ay
- Division of Haematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
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7
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Arcelus JI, Gouin-Thibault I, Samama CM. European guidelines on peri-operative venous thromboembolism prophylaxis: first update.: Chapter 10: Surgery in the obese patient. Eur J Anaesthesiol 2024; 41:607-611. [PMID: 38957028 DOI: 10.1097/eja.0000000000002000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/04/2024]
Affiliation(s)
- Juan Ignacio Arcelus
- From the Department of Surgery. Hospital Universitario Virgen de las Nieves and University of Granada, Spain; Spanish Association of Surgeons (JIA), Department of Laboratory Hematology, Pontchaillou University Hospital of Rennes, IRSET-INSERM-1085, Univ Rennes, France, ISTH (IG-T), Department of Anaesthesia, Intensive Care and Peri-operative Medicine GHU AP-HP, Centre - Université Paris- Cité - Cochin Hospital, Paris, France, ESAIC (CMS)
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8
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Talasaz AH, Sadeghipour P, Ortega-Paz L, Kakavand H, Aghakouchakzadeh M, Beavers C, Fanikos J, Eikelboom JW, Siegal DM, Monreal M, Jimenez D, Vaduganathan M, Castellucci LA, Cuker A, Barnes GD, Connors JM, Secemsky EA, Van Tassell BW, De Caterina R, Kurlander JE, Aminian A, Piazza G, Goldhaber SZ, Moores L, Middeldorp S, Kirtane AJ, Elkind MSV, Angiolillo DJ, Konstantinides S, Lip GYH, Stone GW, Cushman M, Krumholz HM, Mehran R, Bhatt DL, Bikdeli B. Optimizing antithrombotic therapy in patients with coexisting cardiovascular and gastrointestinal disease. Nat Rev Cardiol 2024; 21:574-592. [PMID: 38509244 DOI: 10.1038/s41569-024-01003-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/21/2024] [Indexed: 03/22/2024]
Abstract
Balancing the safety and efficacy of antithrombotic agents in patients with gastrointestinal disorders is challenging because of the potential for interference with the absorption of antithrombotic drugs and for an increased risk of bleeding. In this Review, we address considerations for enteral antithrombotic therapy in patients with cardiovascular disease and gastrointestinal comorbidities. For those with gastrointestinal bleeding (GIB), we summarize a general scheme for risk stratification and clinical evidence on risk reduction approaches, such as limiting the use of concomitant medications that increase the risk of GIB and the potential utility of gastrointestinal protection strategies (such as proton pump inhibitors or histamine type 2 receptor antagonists). Furthermore, we summarize the best available evidence and potential gaps in our knowledge on tailoring antithrombotic therapy in patients with active or recent GIB and in those at high risk of GIB but without active or recent GIB. Finally, we review the recommendations provided by major medical societies, highlighting the crucial role of teamwork and multidisciplinary discussions to customize the antithrombotic regimen in patients with coexisting cardiovascular and gastrointestinal diseases.
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Affiliation(s)
- Azita H Talasaz
- Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Department of Pharmacy Practice, Long Island University, New York, NY, USA
- Division of Pharmacy, New York-Presbyterian/Columbia University Irvine Medical Center, New York, NY, USA
- Department of Pharmacotherapy and Outcome Sciences, Virginia Commonwealth University, Richmond, VA, USA
| | - Parham Sadeghipour
- Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Luis Ortega-Paz
- Division of Cardiology, University of Florida College of Medicine, Jacksonville, FL, USA
| | - Hessam Kakavand
- Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Clinical Pharmacy, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran
| | | | - Craig Beavers
- University of Kentucky College of Pharmacy, Lexington, KY, USA
| | - John Fanikos
- Department of Pharmacy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - John W Eikelboom
- Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada
| | - Deborah M Siegal
- Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Manuel Monreal
- Department of Internal Medicine, Hospital Universitari Germans Trials i Pujol, Universidad Católica San Antonio de Murcia, Barcelona, Spain
| | - David Jimenez
- Respiratory Department, Hospital Ramón y Cajal and Medicine Department, Universidad de Alcalá (IRYCIS), Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, ISCIII, Madrid, Spain
| | - Muthiah Vaduganathan
- Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Lana A Castellucci
- Department of Medicine, Ottawa Hospital Research Institute at the University of Ottawa, Ottawa, Ontario, Canada
| | - Adam Cuker
- Department of Medicine and Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Geoffrey D Barnes
- Frankel Cardiovascular Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Jean M Connors
- Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Eric A Secemsky
- Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
- Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
- Penn Cardiovascular Outcomes, Quality, & Evaluative Research Center, Cardiovascular Medicine Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Benjamin W Van Tassell
- Department of Pharmacotherapy and Outcome Sciences, Virginia Commonwealth University, Richmond, VA, USA
| | - Raffaele De Caterina
- Cardiology Division, Pisa University Hospital, Pisa, Italy
- Fondazione Villa Serena per la Ricerca, Città Sant'Angelo, Pescara, Italy
| | - Jacob E Kurlander
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
- Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA
- VA Ann Arbor Center for Clinical Management Research, Ann Arbor, MI, USA
| | - Ali Aminian
- Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Cleveland, OH, USA
| | - Gregory Piazza
- Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Samuel Z Goldhaber
- Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Lisa Moores
- F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | - Saskia Middeldorp
- Department of Internal Medicine, Radboud Institute of Health Sciences (RIHS), Radboud University Medical Center, Nijmegen, Netherlands
| | - Ajay J Kirtane
- Cardiovascular Research Foundation, New York, NY, USA
- Division of Cardiology, New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, NY, USA
| | - Mitchell S V Elkind
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
| | - Dominick J Angiolillo
- Division of Cardiology, University of Florida College of Medicine, Jacksonville, FL, USA
| | - Stavros Konstantinides
- Center for Thrombosis and Hemostasis, Johannes Gutenberg, University of Mainz, Mainz, Germany
| | - Gregory Y H Lip
- Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, UK
- Danish Center for Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Gregg W Stone
- Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Mary Cushman
- University of Vermont Medical Center, Burlington, VT, USA
| | - Harlan M Krumholz
- Yale New Haven Hospital/Yale Center for Outcomes Research and Evaluation, New Haven, CT, USA
- Department of Health Policy and Management, Yale School of Public Health, New Haven, CT, USA
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA
| | - Roxana Mehran
- Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Deepak L Bhatt
- Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Behnood Bikdeli
- Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
- VA Ann Arbor Center for Clinical Management Research, Ann Arbor, MI, USA.
- Yale New Haven Hospital/Yale Center for Outcomes Research and Evaluation, New Haven, CT, USA.
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9
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Gomes R, Costa-Pinho A, Ramalho-Vasconcelos F, Sousa-Pinto B, Santos-Sousa H, Resende F, Preto J, Lima-da-Costa E. Portomesenteric Venous Thrombosis after Bariatric Surgery: A Case Series and Systematic Review Comparing LSG and LRYGB. J Pers Med 2024; 14:722. [PMID: 39063976 PMCID: PMC11277930 DOI: 10.3390/jpm14070722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 06/25/2024] [Accepted: 07/01/2024] [Indexed: 07/28/2024] Open
Abstract
(1) Background: Portomesenteric Venous Thrombosis (PMVT) is a rare but serious complication of Metabolic Bariatric Surgery (MBS). Although more frequently reported after laparoscopic sleeve gastrectomy (LSG), the risk factors for PMVT remain unclear. This study aims to compare the incidence and determinants of PMVT between LSG and laparoscopic Roux-en-Y gastric bypass (LRYGB). (2) Methods: A retrospective analysis of 5235 MBSs conducted at our institution between 2015 and 2023 identified five cases of PMVT. Additionally, a systematic review in March 2023, covering PubMed, Web of Science and Scopus, was performed. Several data were analyzed regarding risk factors. (3) Results: In our case series, the incidence of PMVT was 0.1%. The five cases described involved four females with a BMI between 39.7 and 56.0 kg/m2. Their comorbidities were associated with metabolic syndrome, all women used oral contraceptive and two patients were diagnosed with thrombophilia or pulmonary embolism. Per protocol, thromboprophylaxis was administered to all patients. Diagnosis was made at a median of 16 days post-surgery, with abdominal pain being the main presenting symptom. Acute cases were managed with enoxaparin, unfractionated heparin and fibrinolysis. One patient required surgery. Ten studies were included in the systematic review and 205 patients with PMVT were identified: 193 (94.1%) post-LSG and 12 post-LRYGB. The most common comorbidities were dyslipidemia, hypertension, diabetes, sleep apnea and liver disorders; (4) Conclusions: PMVT is a potentially life-threatening complication after MBS, requiring preventive measures, timely diagnosis and several treatments. Our findings suggest a higher occurrence in women with an elevated BMI and post-LSG. Tailored thromboprophylaxis for MBS patients at risk of PMVT may be warranted.
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Affiliation(s)
- Raquel Gomes
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (R.G.)
| | - André Costa-Pinho
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (R.G.)
- Obesity Integrated Responsibility Unit (CRI-O), São João Local Health Unit, 4200-319 Porto, Portugal
| | | | - Bernardo Sousa-Pinto
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (R.G.)
- MEDCIDS—Department of Community Medicine, Information and Health Decision Sciences, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
- CINTESIS—Centre for Health Technologies and Services Research, University of Porto, 4200-319 Porto, Portugal
| | - Hugo Santos-Sousa
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (R.G.)
- Obesity Integrated Responsibility Unit (CRI-O), São João Local Health Unit, 4200-319 Porto, Portugal
| | - Fernando Resende
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (R.G.)
- Obesity Integrated Responsibility Unit (CRI-O), São João Local Health Unit, 4200-319 Porto, Portugal
| | - John Preto
- Obesity Integrated Responsibility Unit (CRI-O), São João Local Health Unit, 4200-319 Porto, Portugal
| | - Eduardo Lima-da-Costa
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (R.G.)
- Obesity Integrated Responsibility Unit (CRI-O), São João Local Health Unit, 4200-319 Porto, Portugal
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10
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Benzakine J, Rial C, Mohamedi N, Messas E, Mauge L, Sapoval M, Gendron N, Khider L. Perioperative management of venous recanalization in a patient with inherited antithrombin deficiency: case report. Res Pract Thromb Haemost 2024; 8:102384. [PMID: 38617049 PMCID: PMC11015152 DOI: 10.1016/j.rpth.2024.102384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 02/20/2024] [Indexed: 04/16/2024] Open
Abstract
Background Inherited antithrombin (AT) deficiency (ATD) is a severe thrombophilia causing venous thromboembolism, which can be complicated by postthrombotic syndrome (PTS). Venous recanalization, used to treat PTS, often requires a temporary withdrawal of anticoagulant therapy. In ATD patients, there is a risk of insufficient perioperative anticoagulation due to altered heparin response. Key Clinical Question There is no consensus on how to manage perioperative anticoagulation in ATD patients. Clinical Approach Warfarin-unfractionated heparin transition could be a more reliable strategy than low-molecular-weight heparin transition because unfractionated heparin anti-Xa activity not only reflects heparin-bound AT but also AT's activity, which correlates strongly with therapeutic anticoagulation. Biological monitoring could thus decrease the number of plasma-derived AT supplementation. Conclusion This study describes a successful perioperative management of anticoagulation for venous recanalization that could be suggested to type 1 ATD patients with PTS.
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Affiliation(s)
- Julie Benzakine
- Innovative Therapies in Haemostasis, INSERM, University Paris Cité, Paris, France
- Hematology Department, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris, Paris, France
| | - Carla Rial
- Innovative Therapies in Haemostasis, INSERM, University Paris Cité, Paris, France
- Hematology Department, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris, Paris, France
| | - Nassim Mohamedi
- Vascular Medicine Department, Assistance Publique Hôpitaux de Paris, Centre-University Paris Cité, Paris, France
| | - Emmanuel Messas
- Vascular Medicine Department, Assistance Publique Hôpitaux de Paris, Centre-University Paris Cité, Paris, France
| | - Laetitia Mauge
- Hematology Department, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris, Paris, France
- Paris Cardiovascular Research Centre, INSERM, Hematology Department, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France
| | - Marc Sapoval
- Paris Cardiovascular Research Centre, INSERM, Hematology Department, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris (APHP-CUP), Paris, France
- Paris Cardiovascular Research Centre, INSERM, Interventional Radiology, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris, Paris, France
| | - Nicolas Gendron
- Innovative Therapies in Haemostasis, INSERM, University Paris Cité, Paris, France
- Hematology Department, Assistance Publique Hôpitaux de Paris, Centre-Université de Paris, Paris, France
| | - Lina Khider
- Innovative Therapies in Haemostasis, INSERM, University Paris Cité, Paris, France
- Vascular Medicine Department, Assistance Publique Hôpitaux de Paris, Centre-University Paris Cité, Paris, France
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11
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Gendron N, Talasaz AH. DOACs: A perfect fit for patients with bariatric surgery? Thromb Res 2024; 235:183-185. [PMID: 38383217 DOI: 10.1016/j.thromres.2024.02.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 01/26/2024] [Accepted: 02/05/2024] [Indexed: 02/23/2024]
Affiliation(s)
- Nicolas Gendron
- Hematology Department, Assistance Publique Hôpitaux de Paris.Centre-Université de Paris (APHP.CUP), F-75015 Paris, France; Paris Cité University, INSERM, Innovative Therapies in Haemostasis, F-75006 Paris, France.
| | - Azita H Talasaz
- Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Department of Pharmacy Practice, Long Island University, New York, NY, USA; Department of Pharmacy, New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, NY, USA; Department of Pharmacotherapy and Outcome Sciences, Virginia Commonwealth University, Richmond, VA, USA
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12
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Dvořáčková E, Pilková A, Matoulek M, Slanař O, Hartinger JM. Bioavailability of Orally Administered Drugs After Bariatric Surgery. Curr Obes Rep 2024; 13:141-153. [PMID: 38172482 DOI: 10.1007/s13679-023-00548-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/11/2023] [Indexed: 01/05/2024]
Abstract
PURPOSE OF REVIEW Oral drug absorption after bariatric surgery is likely to be altered, but the impact of different bariatric surgery procedures on individual drugs is not uniform. The aim of this article is to describe factors influencing the bioavailability of orally administered drugs after bariatric surgery and to provide readers with practical recommendations for drug dosing. We also discuss the medications that may be harmful after bariatric surgery. RECENT FINDINGS The fundamental factors for enteral drug absorption are the production of gastric acid; the preserved length of the intestine, i.e., the size of the absorption surface and/or the preserved enterohepatic circulation; and the length of common loop where food and drugs are mixed with digestive enzymes and bile acids. Bypassing of metabolizing enzymes or efflux pumps and changes in intestinal motility can also play an important role. Significant changes of drug absorption early after the anatomic alteration may also be gradually ameliorated due to gradual intestinal adaptation. The most affected drugs are those with low or variable bioavailability and those undergoing enterohepatic circulation. Attention should also be paid to oral drug formulations, especially in the early postoperative period, when immediate-release and liquid formulations are preferred. The changes in oral bioavailability are especially clinically meaningful in patients treated with drugs possessing narrow therapeutic index (e.g., oral anticoagulants, levothyroxine, and anticonvulsants) or in acute conditions (e.g., anti-infectives); nevertheless, it may also influence the therapeutic value of chronic therapy (e.g., antidepressants. antihypertensives, antiplatelets, statins, PPIs, contraceptives, and analgesics); therapeutic effect of chronic therapy is further influenced by pharmacokinetic alterations resulting from weight loss. Therapeutic drug monitoring, periodical clinical evaluation, and adequate dose adjustments are necessary. Due to safety reasons, patients should avoid oral bisphosphonates, regular use of non-steroidal anti-inflammatory drugs, and, if possible, corticosteroids after bariatric surgery.
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Affiliation(s)
- Eliška Dvořáčková
- Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
- Department of Clinical Pharmacy, Hospital Na Františku, Prague, Czech Republic
| | - Alena Pilková
- Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
| | - Martin Matoulek
- Third Internal Department of Endocrinology and Metabolism, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
| | - Ondřej Slanař
- Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
| | - Jan Miroslav Hartinger
- Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
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13
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Bhat RV, Young G, Sharathkumar AA. How I treat pediatric venous thromboembolism in the DOAC era. Blood 2024; 143:389-403. [PMID: 37390311 PMCID: PMC10862368 DOI: 10.1182/blood.2022018966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 06/06/2023] [Accepted: 06/06/2023] [Indexed: 07/02/2023] Open
Abstract
ABSTRACT The direct oral anticoagulants (DOACs) rivaroxaban and dabigatran are newly licensed for the treatment and prevention of venous thromboembolism (VTE) in children and mark a renaissance in pediatric anticoagulation management. They provide a convenient option over standard-of-care anticoagulants (heparins, fondaparinux, and vitamin K antagonists) because of their oral route of administration, child-friendly formulations, and significant reduction in monitoring. However, limitations related to therapeutic monitoring when needed and the lack of approved reversal agents for DOACs in children raise some safety concerns. There is accumulating experience of safety and efficacy of DOACs in adults for a broad scope of indications; however, the cumulative experience of using DOACs in pediatrics, specifically for those with coexisting chronic illnesses, is sparse. Consequently, clinicians must often rely on their experience for treating VTE and extrapolate from data in adults while using DOACs in children. In this article, the authors share their experience of managing 4 scenarios that hematologists are likely to encounter in their day-to-day practice. Topics addressed include (1) appropriateness of indication; (2) use for special populations of children; (3) considerations for laboratory monitoring; (4) transition between anticoagulants; (5) major drug interactions; (6) perioperative management; and (7) anticoagulation reversal.
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Affiliation(s)
- Rukhmi V. Bhat
- Center for Cancer and Blood Disorders, Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Guy Young
- Cancer and Blood Disorders Institute, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA
| | - Anjali A. Sharathkumar
- Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA
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14
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Qiao J, Tran MH. Challenges to Laboratory Monitoring of Direct Oral Anticoagulants. Clin Appl Thromb Hemost 2024; 30:10760296241241524. [PMID: 38650302 PMCID: PMC11036927 DOI: 10.1177/10760296241241524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 03/05/2024] [Accepted: 03/07/2024] [Indexed: 04/25/2024] Open
Abstract
Direct oral anticoagulants (DOACs) exert anticoagulation effect by directly inhibiting Factor Xa (rivaroxaban, apixaban, and edoxaban) or thrombin (dabigatran). Though DOACs are characterized by fixed-dose prescribing and generally do not require routine laboratory drug-level monitoring (DLM), circumstances may arise where the DLM may aid in clinical decision-making, including DOAC dose adjustment, anticoagulant class change, or decisions to withhold or administer reversal agents. We review the current literature that describes high-risk patient groups in which DLM may be beneficial for improved patient anticoagulation management and stewardship. The review also summarizes the limitations of conventional coagulation testing and discuss the emerging utility of quantitative methods for routine and rapid emergent evaluation of DOAC drug levels-in particular, the Anti-Xa activity to detect Factor Xa Inhibitors (rivaroxaban, apixaban, and edoxaban). Both technical and regulatory barriers to widespread DLM implementation are limiting factors to further clinical research that must be overcome, in order to propose universal DOAC DLM strategies and provide clinical-laboratory correlation to formally classify high-risk patient groups.
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Affiliation(s)
- Jesse Qiao
- Irvine Department of Pathology and Laboratory Medicine, University of California, Orange, CA, USA
| | - Minh-Ha Tran
- Irvine Department of Pathology and Laboratory Medicine, University of California, Orange, CA, USA
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15
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Kessler A, Kolben Y, Puris G, Ellis M, Alperin M, Simovich V, Lerman Shivek H, Muszkat M, Maaravi Y, Biton Y. Direct Oral Anticoagulants in Special Patient Populations. J Clin Med 2023; 13:216. [PMID: 38202223 PMCID: PMC10779957 DOI: 10.3390/jcm13010216] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 12/25/2023] [Accepted: 12/26/2023] [Indexed: 01/12/2024] Open
Abstract
Anticoagulants are a cornerstone of treatment in atrial fibrillation. Nowadays, direct oral anticoagulants (DOACs) are extensively used for this condition in developed countries. However, DOAC treatment may be inappropriate in certain patient populations, such as: patients with chronic kidney disease in whom DOAC concentrations may be dangerously elevated; frail elderly patients with an increased risk of falls; patients with significant drug-drug interactions (DDI) affecting either DOAC concentration or effect; patients at the extremes of body mass in whom an "abnormal" volume of distribution may result in inappropriate drug concentrations; patients with recurrent stroke reflecting an unusually high thromboembolic tendency; and, lastly, patients who experience major hemorrhage on an anticoagulant and in whom continued anticoagulation is deemed necessary. Herein we provide a fictional case-based approach to review the recommendations for the use of DOACs in these special patient populations.
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Affiliation(s)
- Asa Kessler
- Heart Institute, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112002, Israel; (A.K.); (Y.K.)
| | - Yotam Kolben
- Heart Institute, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112002, Israel; (A.K.); (Y.K.)
| | - Gal Puris
- Faculty of Medicine, Institute for Research in Military Medicine, Hebrew University of Jerusalem, Israel Defense Force Medical Corps, Jerusalem 9112002, Israel;
| | - Martin Ellis
- Hematology Institute and Blood Bank, Meir Medical Center, Kfar Saba 4428164, Israel;
- Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Mordechai Alperin
- Department of Family Medicine, The Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3200003, Israel;
- Clalit Health Services, Haifa and Western Galilee District, Tel Aviv 6209804, Israel
| | | | - Hila Lerman Shivek
- Hospital Pharmacy Department, Hospitals Division, Clalit Health Services, Tel Aviv 6209804, Israel;
- Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112002, Israel
| | - Mordechai Muszkat
- Department of Medicine, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Mt. Scopus, Jerusalem 9112002, Israel;
| | - Yoram Maaravi
- The Jerusalem Institute of Aging Research, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112002, Israel;
- Department of Geriatrics and Rehabilitation and the Center for Palliative Care, Hadassah Medical Center, Jerusalem 9371125, Israel
| | - Yitschak Biton
- Heart Institute, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112002, Israel; (A.K.); (Y.K.)
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16
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Hindley B, Lip GYH, McCloskey AP, Penson PE. Pharmacokinetics and pharmacodynamics of direct oral anticoagulants. Expert Opin Drug Metab Toxicol 2023; 19:911-923. [PMID: 37991392 DOI: 10.1080/17425255.2023.2287472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 11/21/2023] [Indexed: 11/23/2023]
Abstract
INTRODUCTION Direct oral anticoagulants (DOACs) have overtaken vitamin K antagonists to become the most widely used method of anticoagulation for most indications. Their stable and predictable pharmacokinetics combined with relatively simple dosing, and the absence of routine monitoring has made them an attractive proposition for healthcare providers. Despite the benefits of DOACs as a class, important differences exist between individual DOAC drugs in respect of their pharmacokinetic and pharmacodynamic profiles with implications for dosing and reversal in cases of major bleeding. AREAS COVERED This review summarizes the state of knowledge relating to the pharmacokinetics of dabigatran (factor IIa/thrombin inhibitor) and apixaban, edoxaban and rivaroxaban (factor Xa) inhibitors. We focus on pharmacokinetic differences between the drugs which may have clinically significant implications. EXPERT OPINION Patient-centered care necessitates a careful consideration of the pharmacokinetic and pharmacodynamic differences between DOACs, and how these relate to individual patient circumstances. Prescribers should be aware of the potential for pharmacokinetic drug interactions with DOACs which may influence prescribing decisions in patients with multiple comorbidities. In order to give an appropriate dose of DOAC drugs, accurate estimation of renal function using the Cockcroft-Gault formula using actual body weight is necessary. An increasing body of evidence supports the use of DOACs in patients who are obese, and this is becoming more routine in clinical practice.
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Affiliation(s)
- B Hindley
- Pharmacy Department, Aintree University Hospital, Liverpool, UK
- Clinical Pharmacy and Therapeutics Research Group, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK
| | - G Y H Lip
- Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK
- Danish Center for Clinical Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - A P McCloskey
- Clinical Pharmacy and Therapeutics Research Group, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK
- Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK
| | - P E Penson
- Clinical Pharmacy and Therapeutics Research Group, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK
- Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK
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17
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Grange C, Rioufol C, Souquet PJ, Assaad S. Anti-coagulant Treatment of Cancer-Associated Thrombosis in Frail Patients: Impact of Frailties on the Management of Drug-Drug Interactions. Clin Pharmacokinet 2023; 62:1523-1531. [PMID: 37824026 PMCID: PMC10582124 DOI: 10.1007/s40262-023-01298-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/10/2023] [Indexed: 10/13/2023]
Abstract
Low molecular weight heparins (LMWH) and anti-Xa direct oral anti-coagulants (DOACs) are recommended for the long-term treatment of cancer-associated thrombosis (CAT) based on well-documented randomised controlled trials. Anti-Xa DOACs are viewed as a first choice for the treatment of patients with CAT. A large number of drug-drug interactions have been reported between DOACs and chemotherapy drugs, modifying circulating levels of DOAC leading to fears of increased bleeding risks or thrombotic recurrence. Progresses in anti-neoplastic therapies have improved the prognosis and the survival, thus increasing the prevalence of frail patients with cancer. However, since frailties tend to be excluded from large trials due to multiple co-morbidities, current guidelines are not fully applicable to this population. The management of these frail patients with CAT is particularly complex and requires a risk assessment on a case-by-case basis with specific focus on cancer, patient-related risk factors and drug-drug interactions. In this brief review we have identified age, co-morbidities and co-medications as key factors of frailty that require careful attention and we have developed a therapeutic decision algorithm to help clinicians optimising the use of anti-coagulants in patients with cancer with CAT, especially in case of anti-Xa DOACs concomitant medications. With the evaluation of the bleeding risk according to the type of cancer, and anticipating drug-drug interactions intensity, taking into account patient frailties allows the optimisation of the anti-coagulant choice. A systematic collaboration between oncologists, vascular pathology specialists and pharmacists is warranted to ensure an optimal patient management. Clinical studies are needed to determine the real impact of these interactions.
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Affiliation(s)
- Claire Grange
- Service de Médecine Interne-Médecine Vasculaire, Hospices Civils de Lyon, CH Lyon Sud, Lyon, France.
| | - Catherine Rioufol
- Hospices Civils de Lyon, CH Lyon Sud, Service de Pharmacie, UCBL1-EA 3738 CICLY, Lyon, France
| | - Pierre-Jean Souquet
- Service de Pneumologie et Oncologie Thoracique, Hospices Civils de Lyon, CH Lyon Sud, Lyon, France
| | - Souad Assaad
- Département d'Oncologie Médicale, Centre Léon Bérard, Lyon, France
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18
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Baiardi G, Cafaro A, Stella M, Caviglia MC, Poeta MG, Cangemi G, Mattioli F. Altered plasma levels of apixaban in major gastrointestinal tract surgery: a case report and review of the literature. Clin Biochem 2023; 118:110613. [PMID: 37451498 DOI: 10.1016/j.clinbiochem.2023.110613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 07/06/2023] [Accepted: 07/08/2023] [Indexed: 07/18/2023]
Abstract
Altered direct oral anticoagulant (DOAC) plasma levels can lead either to spontaneous hemorrhagic or thrombotic complications. We describe a case of suspected altered apixaban disposition in a patient with an upper gastrointestinal cancer resection treated with apixaban for non-valvular atrial fibrillation. Diagnosis of ischemic stroke for left hemiparesis was confirmed due to recent emergence of a hypodense area in the posterior capsular nucleus of ischemic reference in a context of binuclear capsular lacunar lesions. Thus, apixaban underexposure was suspected from anamnestic data and oral anticoagulation was switched to parenteral at the next scheduled dose for stroke recurrence. Before switching apixaban pharmacokinetic analysis was performed and unexpectedly showed apixaban plasma overexposure. After 3 days from the switch, the patient experienced spontaneous bleeding complications, for which the risk-benefit profile of continuing anticoagulant treatment for stroke recurrences warranted treatment discontinuation. Unexpected DOAC plasma exposure may present in special patient populations with thrombotic and bleeding complications. Though universally recognized therapeutic ranges have yet to be established for DOACs, periodic drug monitoring may aid in guiding optimization of DOAC therapy and reduce the risk of adverse events in special patient populations.
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Affiliation(s)
- Giammarco Baiardi
- Clinical Pharmacology Unit, Ente Ospedaliero Ospedali Galliera, Genoa, Italy; Pharmacology & Toxicology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy.
| | - Alessia Cafaro
- Pharmacology & Toxicology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy; Chromatography and Mass Spectrometry Section, Central Laboratory of Analysis, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Manuela Stella
- Clinical Pharmacology Unit, Ente Ospedaliero Ospedali Galliera, Genoa, Italy; Pharmacology & Toxicology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Michela Cameran Caviglia
- Clinical Pharmacology Unit, Ente Ospedaliero Ospedali Galliera, Genoa, Italy; Pharmacology & Toxicology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | | | - Giuliana Cangemi
- Chromatography and Mass Spectrometry Section, Central Laboratory of Analysis, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Francesca Mattioli
- Clinical Pharmacology Unit, Ente Ospedaliero Ospedali Galliera, Genoa, Italy; Pharmacology & Toxicology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
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19
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Zúñiga GA, Kandula P, Sandefur H, Tafur AJ. A Patient with Recurrent Strokes: Approach to Coagulopathy. TH OPEN 2023; 7:e262-e269. [PMID: 37772086 PMCID: PMC10533221 DOI: 10.1055/a-2161-1262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 08/15/2023] [Indexed: 09/30/2023] Open
Abstract
Despite anticoagulation recommendations, patients may present with recurrent events. While medication adherence is always a concern, assessment of anticoagulation failure demands a systematic approach, taking into account the potential limitations of anticoagulants and a review of differential diagnoses for comorbidities. We illustrate our approach in a case presentation.
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Affiliation(s)
| | - Pranav Kandula
- Division of Cardiology, NorthShore University HealthSystem, Evanston, Illinois, United States
- College of Engineering, Ohio State University, Columbus, Ohio, United States
| | - Hardy Sandefur
- Division of Cardiology, NorthShore University HealthSystem, Evanston, Illinois, United States
| | - Alfonso J. Tafur
- Division of Cardiology, NorthShore University HealthSystem, Evanston, Illinois, United States
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20
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Zaccone V, Santoro L, Guerrieri E, Diblasi I, Roncarati I, Viticchi G, Vecchiarelli P, Santoliquido A, Fiore F, Molfino A, Landi F, Moroncini G, Gasbarrini A, Muscaritoli M, Falsetti L. Prevention and treatment of catheter-related venous thrombosis in long-term parenteral nutrition: A SINuC position statement. Front Nutr 2023; 10:1106327. [PMID: 36814508 PMCID: PMC9940014 DOI: 10.3389/fnut.2023.1106327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Accepted: 01/13/2023] [Indexed: 02/08/2023] Open
Abstract
The implementation of long-term parenteral nutrition (PN) often requires the placement of central venous access, a procedure that carries a considerable risk of catheter-related venous thrombosis (CRT). The occurrence of CRT represents a major event in the natural history of patients in PN since it can lead to central venous access loss and PN failure. Despite the importance of this topic in clinical nutrition, the prevention and treatment of CRT in PN represents one of the "gray areas" of the literature of the presence of few randomized controlled clinical trials and the generally low level of evidence of published scientific papers. Through a narrative review of the literature and a Delphi consensus, the Italian Society of Clinical Nutrition and Metabolism (SINuC) aimed to collect some practical recommendations regarding the current state-of-the-art in the prevention, diagnosis, and treatment of CRT in patients undergoing long-term PN.
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Affiliation(s)
- Vincenzo Zaccone
- Internal and Emergency Medicine, Marche University Hospital, Ancona, Italy
| | - Luca Santoro
- Department of Cardiovascular and Thoracic Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy,*Correspondence: Luca Santoro, ; orcid.org/0000-0003-3614-7314
| | - Emanuele Guerrieri
- Emergency Medicine Residency Program, Marche Polytechnic University, Ancona, Italy
| | - Ilaria Diblasi
- Emergency Medicine Residency Program, Marche Polytechnic University, Ancona, Italy
| | - Ilaria Roncarati
- Emergency Medicine Residency Program, Marche Polytechnic University, Ancona, Italy
| | | | | | - Angelo Santoliquido
- Department of Cardiovascular and Thoracic Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy,Università Cattolica del Sacro Cuore, Rome, Italy
| | - Francesca Fiore
- Department of Geriatrics and Orthopedics, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Alessio Molfino
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Francesco Landi
- Università Cattolica del Sacro Cuore, Rome, Italy,Department of Geriatrics and Orthopedics, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | | | - Antonio Gasbarrini
- Università Cattolica del Sacro Cuore, Rome, Italy,Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Maurizio Muscaritoli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Lorenzo Falsetti
- Internal and Emergency Medicine, Marche University Hospital, Ancona, Italy
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21
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The Impact of P-Glycoprotein on Opioid Analgesics: What's the Real Meaning in Pain Management and Palliative Care? Int J Mol Sci 2022; 23:ijms232214125. [PMID: 36430602 PMCID: PMC9695906 DOI: 10.3390/ijms232214125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 11/01/2022] [Accepted: 11/11/2022] [Indexed: 11/18/2022] Open
Abstract
Opioids are widely used in cancer and non-cancer pain management. However, many transporters at the blood-brain barrier (BBB), such as P-glycoprotein (P-gp, ABCB1/MDR1), may impair their delivery to the brain, thus leading to opioid tolerance. Nonetheless, opioids may regulate P-gp expression, thus altering the transport of other compounds, namely chemotherapeutic agents, resulting in pharmacoresistance. Other kinds of painkillers (e.g., acetaminophen, dexamethasone) and adjuvant drugs used for neuropathic pain may act as P-gp substrates and modulate its expression, thus making pain management challenging. Inflammatory conditions are also believed to upregulate P-gp. The role of P-gp in drug-drug interactions is currently under investigation, since many P-gp substrates may also act as substrates for the cytochrome P450 enzymes, which metabolize a wide range of xenobiotics and endobiotics. Genetic variability of the ABCB1/MDR1 gene may be accountable for inter-individual variation in opioid-induced analgesia. P-gp also plays a role in the management of opioid-induced adverse effects, such as constipation. Peripherally acting mu-opioid receptors antagonists (PAMORAs), such as naloxegol and naldemedine, are substrates of P-gp, which prevent their penetration in the central nervous system. In our review, we explore the interactions between P-gp and opioidergic drugs, with their implications in clinical practice.
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Saviano A, Brigida M, Petruzziello C, Candelli M, Gabrielli M, Ojetti V. Gastrointestinal Bleeding Due to NOACs Use: Exploring the Molecular Mechanisms. Int J Mol Sci 2022; 23:13955. [PMID: 36430433 PMCID: PMC9698754 DOI: 10.3390/ijms232213955] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 11/09/2022] [Accepted: 11/10/2022] [Indexed: 11/16/2022] Open
Abstract
Novel oral anticoagulants (NOACs) are drugs approved for the prevention and treatment of many thromboembolic cardiovascular conditions as a safer alternative to warfarin. We reviewed studies published in PubMed®, UpToDate®, Web of Science®, and Cochrane® about NOACs' risks and benefits in patients requiring anticoagulation, with a focus on gastrointestinal bleeding and on molecular and pathophysiological mechanisms underlying the risk of bleeding in patients treated with them. Apixaban resulted in a lower rate of gastrointestinal bleeding compared to dabigatran and rivaroxaban. However, data reported that gastrointestinal bleeding in patients treated with NOACs was less severe compared to warfarin. Studies show promising results on the increased and widespread use of NOACs in patients who require anticoagulation (for example-in case of atrial fibrillation or high risk of venous thromboembolism), reporting an overall lower risk of major bleeding events. The profile of NOACs was more effective and secure compared to warfarin, but a more careful medical prescription is required in patients who are at high risk of gastrointestinal bleeding.
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Affiliation(s)
- Angela Saviano
- Department of Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli, 00168 Rome, Italy
| | - Mattia Brigida
- Gastroenterology Unit, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
| | - Carmine Petruzziello
- Department of Emergency Medicine, San Carlo di Nancy Hospital, GVM Research, 00165 Rome, Italy
| | - Marcello Candelli
- Department of Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli, 00168 Rome, Italy
| | - Maurizio Gabrielli
- Department of Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli, 00168 Rome, Italy
| | - Veronica Ojetti
- Department of Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli, 00168 Rome, Italy
- Department of Emergency Medicine, Catholic University of the Sacred Heart, 00168 Rome, Italy
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Harrigan AM, Rioux J, Shivakumar S. Practical Considerations for the Management of Cancer-Associated Venous Thromboembolism: A Guide for the General Oncology Practitioner. Curr Oncol 2022; 29:6419-6432. [PMID: 36135074 PMCID: PMC9497708 DOI: 10.3390/curroncol29090505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 08/31/2022] [Accepted: 09/02/2022] [Indexed: 11/16/2022] Open
Abstract
Cancer-associated venous thromboembolism is a devastating complication of cancer and is associated with significant morbidity and mortality. The cornerstone of cancer-associated venous thromboembolism treatment is anticoagulation, and in recent years, there have been notable randomized clinical trials that have revealed insights into the efficacy and safety of direct oral anticoagulants and low-molecular-weight heparin in the treatment of cancer-associated thrombosis. Deciding on the ideal anticoagulation treatment plan for a patient with a cancer-associated thrombosis is a complex task that requires an understanding of clinical trial data, society guidelines, and, most importantly, consideration of many cancer-related, treatment-related, and patient-related factors. This article summarizes important factors to consider when deciding on anticoagulation therapy for a patient with cancer-associated thrombosis.
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Affiliation(s)
- Amye M. Harrigan
- Department of Medicine, Division of Hematology, Dalhousie University, Nova Scotia Health, Halifax, NS B3H 2Y9, Canada
| | - Josée Rioux
- Department of Pharmacy, Nova Scotia Health, Victoria General Site, Halifax, NS B3H 2Y9, Canada
| | - Sudeep Shivakumar
- Department of Medicine, Division of Hematology, Dalhousie University, Nova Scotia Health, Halifax, NS B3H 2Y9, Canada
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Leong R, Chu DK, Crowther MA, Mithoowani S. Direct oral anticoagulants after bariatric surgery-What is the evidence? J Thromb Haemost 2022; 20:1988-2000. [PMID: 35844166 DOI: 10.1111/jth.15823] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 06/29/2022] [Accepted: 07/13/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Obesity is a global epidemic and bariatric surgery is used with increasing frequency to treat its complications. The extent to which bariatric surgery alters the efficacy, safety, and pharmacokinetics of direct oral anticoagulants (DOACs) is unknown. AIMS In this review, we summarize the evidence supporting the use of DOACs after bariatric surgery and apply our findings to resolve several clinical cases. MATERIALS & METHODS We systematically searched MEDLINE, EMBASE, Cochrane Library, CINAHL and ClinicalTrials.gov from January 1, 2000, to June 15, 2021 for randomized and non-randomized studies evaluating the use of DOACs for any indication after bariatric surgery. Two reviewers independently screened titles, abstracts, and full-text articles. Clinical and pharmacokinetic outcomes were pooled by random-effects meta-analysis with inverse variance weighting. We used the Newcastle-Ottawa scale to assess risk of bias in non-randomized studies and assessed the certainty of evidence with GRADE. RESULTS From 2519 records, we included 28 studies (n = 3229 patients): no randomized trials, 7 cohort studies, 6 case series, and 15 case reports. Incidence rates for arterial thromboembolism, venous thromboembolism and major bleeding were: 0.73 (95% confidence interval [CI]: 0.01-5.10), 2.45 (95% CI: 0.40-7.94), and 3.40 (95% CI: 0.80-9.36) events per 100 patient-years, respectively. The pooled proportion of peak direct oral anticoagulant drug levels within the expected range was 58% (95% CI: 39%-74%). CONCLUSION There appears be substantial risk of DOAC malabsorption after bariatric surgery that could affect clinical outcomes, however the certainty of evidence was very low. PROSPERO CRD42020202636.
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Affiliation(s)
- Russell Leong
- Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada
| | - Derek K Chu
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Mark A Crowther
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Siraj Mithoowani
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
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Outcomes with direct acting oral anticoagulants in patients with a history of bariatric surgery: a retrospective cohort study. Surg Obes Relat Dis 2022. [DOI: 10.1016/j.soard.2022.09.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Ramcharitar RK, Man L, Khaja MS, Barnett ME, Sharma A. A Review of the Past, Present and Future of Cancer-associated Thrombosis Management. Heart Int 2022; 16:117-123. [PMID: 36721704 PMCID: PMC9870322 DOI: 10.17925/hi.2022.16.2.117] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 06/14/2022] [Indexed: 12/25/2022] Open
Abstract
Venous thromboembolism (VTE) can have a significant impact on the management, quality of life and mortality of patients with cancer. VTE occurs in 5-20% of patients with cancer, and malignancy is associated with up to 25% of all VTE. It is the second leading cause of death in ambulatory patients with cancer who are receiving chemotherapy. Increased rates of cancer-associated thrombosis are attributed to improved patient survival, increased awareness, surgery, antineoplastic treatments and the use of central venous access devices. Many factors influence cancer-associated thrombosis risk and are broadly categorized into patient-related, cancer-related and treatment-related risks. Direct-acting oral anticoagulants have shown themselves to be at least as effective in preventing recurrent VTE in patients with cancer with symptomatic and incidental VTE. This has led to a change in treatment paradigms so that direct-acting oral anticoagulants are now considered first-line agents in appropriately selected patients. In this article, we review the prior and recent landmark studies that have directed the treatment of cancer-associated thrombosis, and discuss specific factors that affect management as well as future treatment considerations.
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Affiliation(s)
| | - Louise Man
- Department of Medicine, University of Virginia, Charlottesville, VA, USA
| | - Minhaj S Khaja
- Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA
| | | | - Aditya Sharma
- Department of Medicine, University of Virginia, Charlottesville, VA, USA
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Hwang HG, Kim YK. Pharmacotherapy for pulmonary embolism: new anticoagulants. JOURNAL OF THE KOREAN MEDICAL ASSOCIATION 2022. [DOI: 10.5124/jkma.2022.65.7.442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Background: Pulmonary embolism is associated with reduced survival and considerable economic burden worldwide. In Korea, the incidence of pulmonary embolism has been gradually increasing. Older individuals are at an increased risk for pulmonary embolism and anticoagulation-related bleeding events. Typically, heparin and vitamin K antagonists are employed to treat pulmonary embolism; however, these agents present numerous limitations. Hence, novel anticoagulants with improved safety and efficacy profiles are urgently needed.Current Concepts: Direct oral anticoagulants (DOACs), including direct thrombin (coagulation factor II) inhibitors and selective inhibitors of coagulation factor Xa, have emerged as alternative agents. Phase III, large-scale clinical trials have revealed that DOACs are non-inferior to standard therapy during initial and long-term treatment of pulmonary embolism, considering the safety profile. Evidence-based clinical guidelines recommend that primary care clinicians employ DOACs over warfarin to achieve anticoagulation.Discussion and Conclusion: For over 70 years, the standard therapy for most patients with pulmonary embolism has involved heparin administration, overlapped and followed by a vitamin K antagonist. Recently developed DOACs against coagulation factor Xa or thrombin might overcome limitations of standard therapy, including the need for injection and regular dose adjustment with laboratory monitoring. These limitations hinder the management of patients with pulmonary embolism and negatively impact the patient’s quality of life. Four DOACs, including apixaban, dabigatran, edoxaban, and rivaroxaban, are currently available for treating pulmonary embolism in Korea, which could simplify the therapeutic strategy.
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Cost-Effectiveness of Aspirin for Extended Venous Thromboembolism Prophylaxis After Major Surgery for Inflammatory Bowel Disease. J Gastrointest Surg 2022; 26:1275-1285. [PMID: 35277799 DOI: 10.1007/s11605-022-05287-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 02/26/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND AND PURPOSE Venous thromboembolism extended prophylaxis after inflammatory bowel disease surgery remains controversial. The purpose of this study was to evaluate if adopting an aspirin-based prophylaxis strategy may address current cost-effectiveness limitations. METHODS A decision analysis model was used to compare costs and outcomes of a reference case patient undergoing inflammatory bowel disease-associated colorectal surgery considered for post-discharge thromboembolism prophylaxis. Low-dose aspirin was compared to an enoxaparin regimen as well as no prophylaxis. Source estimates were obtained from aggregated existing literature. Secondary analysis included out-of-pocket costs. A 10,000-simulation Monte Carlo probabilistic sensitivity analysis accounted for uncertainty in model estimates. RESULTS An enoxaparin-based regimen compared to aspirin demonstrated an unfavorable incremental cost-effectiveness ratio of $908,268 per quality-adjusted life year. Sensitivity analysis supported this finding in > 75% of simulated cases; scenarios favoring enoxaparin included those with > 4% post-discharge event rates. Aspirin versus no prophylaxis demonstrated a favorable ratio of $106,601 per quality-adjusted life year. Findings were vulnerable to a post-discharge thromboembolism rate < 1%, aspirin-associated bleeding rate > 1%, median hospital costs of bleeding > 3 × , and decreased efficacy of aspirin (RR > 0.75). The average out-of-pocket cost of choosing an aspirin ePpx strategy increased by $54 per patient versus $708 per patient with enoxaparin. CONCLUSIONS Low-dose aspirin extended prophylaxis following inflammatory bowel disease surgery has a favorable cost-safety profile and may be an attractive alternative approach.
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29
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Postoperative anticoagulation in vascular reconstructions associated with malignancies. Ann Vasc Surg 2022; 86:219-228. [DOI: 10.1016/j.avsg.2022.04.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 03/20/2022] [Accepted: 04/05/2022] [Indexed: 11/22/2022]
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Absorption of Direct Oral Anticoagulants in Cancer Patients after Gastrectomy. Pharmaceutics 2022; 14:pharmaceutics14030662. [PMID: 35336036 PMCID: PMC8951361 DOI: 10.3390/pharmaceutics14030662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Revised: 03/08/2022] [Accepted: 03/10/2022] [Indexed: 11/30/2022] Open
Abstract
Direct oral anticoagulants (DOACs) are safe and effective in cancer patients treated for venous thromboembolism (VTE) or atrial fibrillation (AF). Gastrectomy is the treatment of choice in patients with localized upper gastrointestinal cancer. DOACs are absorbed in the upper gastrointestinal tract, but to what extent is unclear. In a retrospective analysis, hospital data were searched for adult patients who underwent gastrectomy for gastroesophageal or pancreatic cancer, and DOAC therapy for VTE or AF after gastrectomy. DOAC blood levels were determined by chromogenic assays before and after administration, and thromboembolic and bleeding complications were recorded. Eleven patients (median age 76 years) received a factor Xa inhibitor (FXaI; apixaban (3), edoxaban (3), rivaroxaban (4)) or the factor IIa inhibitor dabigatran (1) for VTE (7) or AF (4) after gastrectomy. Eight patients on FXaI had anti-Xa (aXa) trough levels within the expected range (ER). In all of them, aXa levels increased upon DOAC administration. Two patients on 30 mg edoxaban had low aXa trough levels. Administration of 20 mg of rivaroxaban resulted in trough levels in the ER in one of them. None of the FXaI patients had thromboembolism, while two experienced bleeding (arterial puncture site, gastrointestinal). One dabigatran AF patient with trough and peak concentrations below the ER had strokes during 110 mg and 150 mg dabigatran administration. While on apixaban, aXa levels were in the ER, and no clinical complications occurred. DOACs, particularly FXaI, were adequately absorbed in cancer patients after gastrectomy. Our observation of recurrent thromboembolic events in a patient treated with dabigatran warrants cautious use in this specific patient population.
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Musgrave K, Power K, Laffan M, O’Donnell JS, Thachil J, Maraveyas A. Practical Treatment Guidance for Cancer-Associated Thrombosis – Managing the Challenging Patient: A Consensus Statement. Crit Rev Oncol Hematol 2022; 171:103599. [PMID: 35065219 DOI: 10.1016/j.critrevonc.2022.103599] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 01/07/2022] [Accepted: 01/17/2022] [Indexed: 02/07/2023] Open
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Klomberg RCW, Vlug LE, de Koning BAE, de Ridder L. Venous Thromboembolic Complications in Pediatric Gastrointestinal Diseases: Inflammatory Bowel Disease and Intestinal Failure. Front Pediatr 2022; 10:885876. [PMID: 35601436 PMCID: PMC9116461 DOI: 10.3389/fped.2022.885876] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 04/08/2022] [Indexed: 12/21/2022] Open
Abstract
In children with gastrointestinal disorders such as inflammatory bowel disease (IBD) and intestinal failure (IF), the risk of venous thromboembolism (VTE) is increased. VTE may lead to pulmonary embolism, sepsis and central line infection, stroke and post-thrombotic syndrome. The purpose of this review is to summarize current knowledge and recent advances around VTE management in pediatric gastroenterology with a focus on IBD and IF. The VTE incidence in children with IBD is reported to be around 4-30 per 10,000 patient-years, with higher incidences for hospitalized children. While in general, IF is less common than IBD, the VTE incidence in children with IF is around 750 per 10,000 patient-years. The most common risk factors for development of VTE involve deviations leading to Virchow's triad (endothelial damage, stasis, and hypercoagulability) and include active inflammation, particularly with colonic involvement, presence of a central venous catheter, underlying thrombophilia, reduced mobility, surgery, and hospitalization. Classes of anticoagulants used for treatment of VTE are low molecular weight heparins and vitamin K antagonists. However, the use of direct oral anticoagulants for treatment or prevention of VTE has not been studied in this pediatric population yet. Pediatric gastroenterologists apply different VTE prevention and treatment strategies due to lack of literature and lack of consensus. We discuss the role of primary and secondary prophylactic use of anticoagulants, and provide tools and recommendations for screening, prevention and management for the specific pediatric populations.
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Affiliation(s)
- Renz C W Klomberg
- Division of Gastroenterology, Department of Pediatrics, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, Netherlands
| | - Lotte E Vlug
- Division of Gastroenterology, Department of Pediatrics, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, Netherlands
| | - Barbara A E de Koning
- Division of Gastroenterology, Department of Pediatrics, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, Netherlands
| | - Lissy de Ridder
- Division of Gastroenterology, Department of Pediatrics, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, Netherlands
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Javed A, Ajmal M, Wolfson A. Dabigatran in cardiovascular disease management: A comprehensive review. World J Cardiol 2021; 13:710-719. [PMID: 35070113 PMCID: PMC8716972 DOI: 10.4330/wjc.v13.i12.710] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 09/27/2021] [Accepted: 11/25/2021] [Indexed: 02/06/2023] Open
Abstract
Dabigatran, a direct thrombin inhibitor, has robust data for the treatment of deep venous thrombosis and pulmonary embolism, stroke prevention in non-valvular atrial fibrillation, and the prophylaxis of venous thromboembolism (VTE) after knee and hip replacement. Recent studies have evaluated dabigatran to determine its safety and efficacy in such conditions as VTE in malignancy, coronary artery disease, mechanical and bioprosthetic valves, and antiphospholipid syndrome. This article provides a comprehensive review on the role of dabigatran in various cardiovascular diseases.
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Affiliation(s)
- Ayesha Javed
- Department of Internal Medicine, University of Arizona, Tucson, AZ 85719, United States
| | - Muhammad Ajmal
- Department of Cardiology, University of Arizona, Tucson, AZ 85719, United States.
| | - Aaron Wolfson
- Department of Cardiology, University of Southern California, Los Angeles, CA 90007, United States
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Hakeam HA, Alkhani M, Alyahya Z, Alawaji Z, Ofori S. Direct Acting Oral Anticoagulants Following Gastrointestinal Tract Surgery. J Cardiovasc Pharmacol 2021; 78:867-874. [PMID: 34882113 DOI: 10.1097/fjc.0000000000001142] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 09/11/2021] [Indexed: 11/26/2022]
Abstract
ABSTRACT Direct-acting oral anticoagulants (DOACs) vary in bioavailability and sites of absorption in the gastrointestinal tract (GIT). Data on DOAC use after major GIT surgery are limited. The aim of this case series was to report the impact of surgical resection or bypass of the GIT on rivaroxaban and apixaban peak plasma concentrations. This was a case series of patients who received rivaroxaban or apixaban after GIT surgery, during the period of July 1, 2019, to December 31, 2020. Peak plasma concentrations of rivaroxaban and apixaban were assessed for the expected concentrations. Of the 27 assessed patients, 18 (66.7%) received rivaroxaban, and 9 (33.3%) received apixaban. After rivaroxaban therapy, 4 of 5 patients (80%) who underwent gastrectomy, and 3 of 3 patients (100%) who underwent duodenum and proximal jejunum exclusion had peak plasma concentrations of rivaroxaban lower than the effective range, whereas 11 of 11 patients (100%) who underwent distal bowel or ileostomy had peak rivaroxaban plasma within the effective range. After apixaban therapy, 5 of 6 patients (83.3%) who underwent total or partial gastrectomy achieved effective peak concentrations. All the patients who underwent proximal and distal bowel resection or bypass had peak concentrations of apixaban within the effective range. In conclusion, surgical resection or bypass of the upper GIT could affect DOAC absorption and subsequently peak plasma concentrations. This effect was more observed among rivaroxaban recipients. An injectable anticoagulant or vitamin K antagonist may be preferred if DOAC concentrations cannot be measured after GIT surgery.
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Affiliation(s)
- Hakeam A Hakeam
- Pharmaceutical Care Division, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Mohammed Alkhani
- Department of Vascular Surgery, Hospices Civils de Lyon, Lyon, France
| | - Zyad Alyahya
- Department of Surgery, Salford Royal NHS Foundation Trust, Manchester, United Kingdom
| | - Ziyad Alawaji
- College of Medicine, Qassim University, Burydah, Saudi Arabia ; and
| | - Sandra Ofori
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
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Steffel J, Collins R, Antz M, Cornu P, Desteghe L, Haeusler KG, Oldgren J, Reinecke H, Roldan-Schilling V, Rowell N, Sinnaeve P, Vanassche T, Potpara T, Camm AJ, Heidbüchel H. 2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation. Europace 2021; 23:1612-1676. [PMID: 33895845 PMCID: PMC11636576 DOI: 10.1093/europace/euab065] [Citation(s) in RCA: 578] [Impact Index Per Article: 144.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Affiliation(s)
- Jan Steffel
- Department of Cardiology, Division of Electrophysiology, University Heart Center Zurich, Switzerland
| | - Ronan Collins
- Age-Related Health Care, Tallaght University Hospital / Department of Gerontology Trinity College, Dublin, Ireland
| | - Matthias Antz
- Department of Electrophysiology, Hospital Braunschweig, Braunschweig, Germany
| | - Pieter Cornu
- Faculty of Medicine and Pharmacy, Research Group Clinical Pharmacology and Clinical Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium
| | - Lien Desteghe
- Cardiology, Antwerp University and University Hospital, Antwerp, Belgium
- Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium
| | | | - Jonas Oldgren
- Uppsala Clinical Research Center and Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Holger Reinecke
- Department of Cardiology I - Coronary and Peripheral Vascular Disease, Heart Failure, University Hospital Münster, Münster, Germany
| | | | | | - Peter Sinnaeve
- Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium
| | - Thomas Vanassche
- Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium
| | | | - A John Camm
- Cardiology Clinical Academic Group, Molecular & Clinical Sciences Institute, St George’s University, London, UK
| | - Hein Heidbüchel
- Cardiology, Antwerp University and University Hospital, Antwerp, Belgium
- Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium
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Meng X, Ahmed M, Courtney KD, Arafat W, Ibrahim I, Margulis V, Nichols C, Bagrodia A. Prophylaxis Against Thromboembolic Events During Chemotherapy for Germ Cell Cancer. Front Oncol 2021; 11:724682. [PMID: 34692501 PMCID: PMC8529113 DOI: 10.3389/fonc.2021.724682] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Accepted: 09/22/2021] [Indexed: 11/13/2022] Open
Abstract
INTRODUCTION Patients with advanced germ cell tumors (GCT) receiving cisplatin-based chemotherapy have high rates of thromboembolic events (TEE) which can negatively affect their overall survival. While primary TEE prophylaxis during chemotherapy may prevent these events, it is unclear which patients will benefit in this setting. MATERIALS AND METHODS A review of PubMed/Medline was conducted in December 2020 and all pertinent articles were evaluated for relevancy and quality of data for inclusion in the review. RESULTS Studies on patients receiving initial cisplatin-based chemotherapy for advanced GCT have reported up to a 19% rate of TEE. This high rate may be associated with multiple factors including retroperitoneal lymphadenopathy, advanced clinical stage, high risk Khorana scores and presence of a central line. Large phase III clinical trials have demonstrated the benefit of low-molecular-weight-heparin and direct oral anticoagulants for primary prophylaxis and against recurrent TEE. However, primary prophylaxis is currently underutilized with GCT patients starting chemotherapy. CONCLUSION Precise models to predict TEE risk and consideration of anticoagulation are difficult to develop owing to the relatively uncommon nature of GCT and lack of representation in primary TEE prophylaxis clinical trials. Despite these limitations, we believe that the benefits of prophylactic anticoagulation outweigh the risk of major bleeding in select GCT patients with higher risk of TEE. We have developed a simple algorithm to help guide TEE prophylaxis selection based on patient factors and route of chemotherapy administration. Given the high rate of TEE in GCT patients, we believe better utilization of primary prophylaxis in patient starting cisplatin-based chemotherapy will have clinical benefit.
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Affiliation(s)
- Xiaosong Meng
- Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, United States
| | - Murtaza Ahmed
- School of Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States
| | - Kevin D Courtney
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States
| | - Waddah Arafat
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States
| | - Ibrahim Ibrahim
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States
| | - Vitaly Margulis
- Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, United States
| | - Craig Nichols
- Testicular Cancer Commons, Portland, OR, United States
| | - Aditya Bagrodia
- Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, United States
- Department of Urology, University of California San Diego, San Diego, CA, United States
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37
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Adverse events in patients taking apixaban or rivaroxaban who have undergone bariatric surgery: a retrospective case series. J Thromb Thrombolysis 2021; 53:601-606. [PMID: 34559367 DOI: 10.1007/s11239-021-02573-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/12/2021] [Indexed: 10/20/2022]
Abstract
Clinical trials comparing direct oral anticoagulants (DOAC) to warfarin excluded patients with a history of bariatric surgery. The anatomic changes from bariatric procedures have several effects on drug absorption which can have serious consequences for these patients. We sought to describe real-world use of DOACs among adults that had a history of bariatric surgery or underwent a bariatric surgery while receiving a DOAC. We conducted a retrospective case series of adult patients, at a large academic medical center, who initiated any DOAC in 2016 thru 2019 and had a history of bariatric surgery or underwent a bariatric surgery while receiving a DOAC. Thrombotic and bleeding events were described using summary statistics and bleeding severity was described using the International Society on Thrombosis and Haemostasis criteria. Twenty-eight patients met the inclusion criteria of having bariatric surgery (Roux-en-Y gastric bypass, sleeve gastrectomy or gastric band) and receiving a DOAC. Twenty (71.4%) were prescribed apixaban and eight (28.6%) were prescribed rivaroxaban. Seven patients (25%) experienced at least one clinically relevant non-major bleeding event, including one patient (3.6%) that had a major bleeding event. Two patients (7.1%) had a thromboembolic event. Coagulation laboratory studies were infrequently performed at the time of the bleeding or clotting events. Among patients with a history of bariatric surgery, use of DOACs were commonly associated with clinically relevant non-major bleeding events and less commonly associated with major bleeding and thromboembolic events. Larger studies may offer further insight into the overall safety and efficacy of DOAC therapy in patients that have undergone bariatric surgery. The specific role of coagulation laboratory studies warrants further evaluation.
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Grześk G, Rogowicz D, Wołowiec Ł, Ratajczak A, Gilewski W, Chudzińska M, Sinkiewicz A, Banach J. The Clinical Significance of Drug-Food Interactions of Direct Oral Anticoagulants. Int J Mol Sci 2021; 22:8531. [PMID: 34445237 PMCID: PMC8395160 DOI: 10.3390/ijms22168531] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 08/05/2021] [Accepted: 08/06/2021] [Indexed: 12/25/2022] Open
Abstract
Cardiovascular diseases are the most common cause of death in the world. For almost 60 years, vitamin K antagonists (VKAs) were the mainstay of anticoagulation therapy, but in recent years direct oral anticoagulants (DOACs) have become the anticoagulant treatment of choice. DOACs were initially considered drugs with no significant food interactions; however, clinical observations from daily practice have proved otherwise as interactions with food ingredients have been reported. Food, dietary supplements or herbs may contain substances that, when administered concomitantly with DOACs, can potentially affect the plasma concentration of the drugs. The aim of this paper was to evaluate the clinical significance of drug-food interactions of DOACs, such as dabigatran, rivaroxaban, apixaban, edoxaban and betrixaban. Patients treated with anticoagulants should avoid products containing St. John's wort and take special care with other food ingredients. As the interest in dietary supplements is on the rise, healthcare providers can contribute to the development of well-designed clinical trials on interactions between DOACs and food, and distribute sufficient knowledge about the proper use of these supplements among patients.
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Affiliation(s)
- Grzegorz Grześk
- Department of Cardiology and Clinical Pharmacology, Faculty of Health Sciences, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Ujejskiego 75 Street, 85-168 Bydgoszcz, Poland; (G.G.); (Ł.W.); (A.R.); (W.G.); (J.B.)
| | - Daniel Rogowicz
- Department of Cardiology and Clinical Pharmacology, Faculty of Health Sciences, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Ujejskiego 75 Street, 85-168 Bydgoszcz, Poland; (G.G.); (Ł.W.); (A.R.); (W.G.); (J.B.)
| | - Łukasz Wołowiec
- Department of Cardiology and Clinical Pharmacology, Faculty of Health Sciences, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Ujejskiego 75 Street, 85-168 Bydgoszcz, Poland; (G.G.); (Ł.W.); (A.R.); (W.G.); (J.B.)
| | - Agnieszka Ratajczak
- Department of Cardiology and Clinical Pharmacology, Faculty of Health Sciences, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Ujejskiego 75 Street, 85-168 Bydgoszcz, Poland; (G.G.); (Ł.W.); (A.R.); (W.G.); (J.B.)
| | - Wojciech Gilewski
- Department of Cardiology and Clinical Pharmacology, Faculty of Health Sciences, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Ujejskiego 75 Street, 85-168 Bydgoszcz, Poland; (G.G.); (Ł.W.); (A.R.); (W.G.); (J.B.)
| | - Małgorzata Chudzińska
- Department of Nutrition and Dietetics, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Dębowa 3 Street, 85-626 Bydgoszcz, Poland;
| | - Anna Sinkiewicz
- Department of Otolaryngology, Audiology and Phoniatrics, University Hospital No. 2, Collegium Medicum, Nicolaus Copernicus University in Toruń, Ujejskiego 75 Street, 85-168 Bydgoszcz, Poland;
| | - Joanna Banach
- Department of Cardiology and Clinical Pharmacology, Faculty of Health Sciences, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Ujejskiego 75 Street, 85-168 Bydgoszcz, Poland; (G.G.); (Ł.W.); (A.R.); (W.G.); (J.B.)
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39
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Martin KA, Beyer-Westendorf J, Davidson BL, Huisman MV, Sandset PM, Moll S. Use of direct oral anticoagulants in patients with obesity for treatment and prevention of venous thromboembolism: Updated communication from the ISTH SSC Subcommittee on Control of Anticoagulation. J Thromb Haemost 2021; 19:1874-1882. [PMID: 34259389 DOI: 10.1111/jth.15358] [Citation(s) in RCA: 139] [Impact Index Per Article: 34.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 04/20/2021] [Accepted: 04/21/2021] [Indexed: 12/27/2022]
Abstract
Although direct-acting oral anticoagulants (DOACs) have widespread first-line use for treatment and prevention of venous thromboembolism (VTE), uncertainty remains regarding their efficacy and safety in patients with obesity. We reviewed available data for use of DOACs for VTE treatment and prevention in patients with obesity, including phase 3, phase 4, meta-analyses, and pharmacokinetic and pharmacodynamics studies. In addition, we reviewed available data regarding DOACs in bariatric surgery. We provide updated guidance recommendations on using DOACs in patients with obesity for treatment and prevention of VTE, as well as following bariatric surgery.
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Affiliation(s)
- Karlyn A Martin
- Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Jan Beyer-Westendorf
- Thrombosis Research Unit, Division Hematology and Hemostasis, Department of Medicine 1, University Hospital, Technische University Dresden, Dresden, Germany
| | - Bruce L Davidson
- Pulmonary and Critical Care Medicine, Washington State University Elson S Floyd College of Medicine and Providence Health System, Seattle, WA, USA
| | - Menno V Huisman
- Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands
| | - Per Morten Sandset
- Department of Hematology, Oslo University Hospital and University of Oslo, Oslo, Norway
| | - Stephan Moll
- Division of Hematology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA
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40
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Choe AR, Moon CM, Tae CH, Chun J, Bang KB, Lee YJ, Lee HS, Jung Y, Park SC, Koo HS. Characteristics, Location, and Clinical Outcomes of Gastrointestinal Bleeding in Patients Taking New Oral Anticoagulants Compared to Vitamin K Antagonists. J Clin Med 2021; 10:jcm10122693. [PMID: 34207296 PMCID: PMC8234640 DOI: 10.3390/jcm10122693] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 06/05/2021] [Accepted: 06/10/2021] [Indexed: 02/07/2023] Open
Abstract
New oral anticoagulants (NOACs) are commonly used in clinical practice as alternatives to vitamin K antagonists (VKA). However, the etiology, clinical course, and risk of gastrointestinal (GI) bleeding remain unclear. We aimed to evaluate the clinical characteristics and location of acute GI bleeding associated with NOACs and its severity and outcomes compared to VKA. This retrospective multicenter study included 381 subjects on anticoagulants who underwent appropriate diagnostic examination due to GI bleeding. Regarding the characteristics of acute GI bleeding, the proportion of vascular lesions was significantly lower in the NOACs group than that in the VKA group. Small bowel bleeding occurred less commonly in the NOACs group, but the difference did not reach statistical significance. Regarding severity and clinical outcomes, patients on NOACs received significantly smaller volumes of transfused blood products and had shorter ICU stays than those on VKA. Moreover, the need for surgery and the risk of rebleeding in the NOACs group were significantly lower than those in the VKA group. Patients on NOACs have better clinical outcomes in terms of severity of acute GI bleeding or rebleeding than patients on VKA. Patients on NOACs demonstrate different characteristics and location of acute GI bleeding than those on VKA.
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Affiliation(s)
- A Reum Choe
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul 07985, Korea; (A.R.C.); (C.H.T.)
| | - Chang Mo Moon
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul 07985, Korea; (A.R.C.); (C.H.T.)
- Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul 07804, Korea
- Correspondence: ; Tel.: +82-2-2650-2945
| | - Chung Hyun Tae
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul 07985, Korea; (A.R.C.); (C.H.T.)
| | - Jaeyoung Chun
- Department of Internal Medicine, Seoul National University College of Medicine, Liver Research Institute, Seoul 03080, Korea;
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea
| | - Ki Bae Bang
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan 31116, Korea;
| | - Yoo Jin Lee
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu 42601, Korea;
| | - Hyun Seok Lee
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41404, Korea;
| | - Yunho Jung
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan 31151, Korea;
| | - Sung Chul Park
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon 24289, Korea;
| | - Hoon Sup Koo
- Department of Internal Medicine, Konyang University College of Medicine, Daejeon 35365, Korea;
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41
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Kirschner M, do Ó Hartmann N, Parmentier S, Hart C, Henze L, Bisping G, Griesshammer M, Langer F, Pabinger-Fasching I, Matzdorff A, Riess H, Koschmieder S. Primary Thromboprophylaxis in Patients with Malignancies: Daily Practice Recommendations by the Hemostasis Working Party of the German Society of Hematology and Medical Oncology (DGHO), the Society of Thrombosis and Hemostasis Research (GTH), and the Austrian Society of Hematology and Oncology (ÖGHO). Cancers (Basel) 2021; 13:2905. [PMID: 34200741 PMCID: PMC8230401 DOI: 10.3390/cancers13122905] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 06/03/2021] [Accepted: 06/04/2021] [Indexed: 12/20/2022] Open
Abstract
Patients with cancer, both hematologic and solid malignancies, are at increased risk for thrombosis and thromboembolism. In addition to general risk factors such as immobility and major surgery, shared by non-cancer patients, cancer patients are exposed to specific thrombotic risk factors. These include, among other factors, cancer-induced hypercoagulation, and chemotherapy-mediated endothelial dysfunction as well as tumor-cell-derived microparticles. After an episode of thrombosis in a cancer patient, secondary thromboprophylaxis to prevent recurrent thromboembolism has long been established and is typically continued as long as the cancer is active or actively treated. On the other hand, primary prophylaxis, even though firmly established in hospitalized cancer patients, has only recently been studied in ambulatory patients. This recent change is mostly due to the emergence of direct oral anticoagulants (DOACs). DOACs have a shorter half-life than vitamin K antagonists (VKA), and they overcome the need for parenteral application, the latter of which is associated with low-molecular-weight heparins (LMWH) and can be difficult for the patient to endure in the long term. Here, first, we discuss the clinical trials of primary thromboprophylaxis in the population of cancer patients in general, including the use of VKA, LMWH, and DOACs, and the potential drug interactions with pre-existing medications that need to be taken into account. Second, we focus on special situations in cancer patients where primary prophylactic anticoagulation should be considered, including myeloma, major surgery, indwelling catheters, or immobilization, concomitant diseases such as renal insufficiency, liver disease, or thrombophilia, as well as situations with a high bleeding risk, particularly thrombocytopenia, and specific drugs that may require primary thromboprophylaxis. We provide a novel algorithm intended to aid specialists but also family practitioners and nurses who care for cancer patients in the decision process of primary thromboprophylaxis in the individual patient.
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Affiliation(s)
- Martin Kirschner
- Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany; (M.K.); (N.d.Ó.H.)
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), 52074 Aachen, Germany
| | - Nicole do Ó Hartmann
- Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany; (M.K.); (N.d.Ó.H.)
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), 52074 Aachen, Germany
| | - Stefani Parmentier
- Oncology and Hematology, Tumor Center, St. Claraspital, 4058 Basel, Switzerland;
| | - Christina Hart
- Department of Hematology and Oncology, Internal Medicine III, University Hospital Regensburg, 93053 Regensburg, Germany;
| | - Larissa Henze
- Department of Medicine, Clinic III—Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, 18057 Rostock, Germany;
| | - Guido Bisping
- Department of Medicine I, Mathias Spital Rheine, 48431 Rheine, Germany;
| | - Martin Griesshammer
- University Clinic for Hematology, Oncology, Haemostaseology and Palliative Care, Johannes Wesling Medical Center Minden, University of Bochum, 32429 Minden, Germany;
| | - Florian Langer
- II.Medical Clinic and Polyclinic, Center for Oncology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany;
| | - Ingrid Pabinger-Fasching
- Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria;
| | - Axel Matzdorff
- Department of Internal Medicine II, Asklepios Clinic Uckermark, 16303 Schwedt, Germany;
| | - Hanno Riess
- Medical Department, Division of Oncology and Hematology, Campus Charité Mitte, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany;
| | - Steffen Koschmieder
- Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany; (M.K.); (N.d.Ó.H.)
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), 52074 Aachen, Germany
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42
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Corsini A, Ferri N, Proietti M, Boriani G. Edoxaban and the Issue of Drug-Drug Interactions: From Pharmacology to Clinical Practice. Drugs 2021; 80:1065-1083. [PMID: 32504376 DOI: 10.1007/s40265-020-01328-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Edoxaban, a direct factor Xa inhibitor, is the latest of the non-vitamin K antagonist oral anticoagulants (NOACs). Despite being marketed later than other NOACs, its use is now spreading in current clinical practice, being indicated for both thromboprophylaxis in patients with non-valvular atrial fibrillation (NVAF) and for the treatment and prevention of venous thromboembolism (VTE). In patients with multiple conditions, the contemporary administration of several drugs can cause relevant drug-drug interactions (DDIs), which can affect drugs' pharmacokinetics and pharmacodynamics. Usually, all the NOACs are considered to have significantly fewer DDIs than vitamin K antagonists; notwithstanding, this is actually not true, all of them are affected by DDIs with drugs that can influence the activity (induction or inhibition) of P-glycoprotein (P-gp) and cytochrome P450 3A4, both responsible for the disposition and metabolism of NOACs to a different extent. In this review/expert opinion, we focused on an extensive report of edoxaban DDIs. All the relevant drugs categories have been examined to report on significant DDIs, discussing the impact on edoxaban pharmacokinetics and pharmacodynamics, and the evidence for dose adjustment. Our analysis found that, despite a restrained number of interactions, some strong inhibitors/inducers of P-gp and drug-metabolising enzymes can affect edoxaban concentration, just as it happens with other NOACs, implying the need for a dose adjustment. However, our analysis of edoxaban DDIs suggests that given the small propensity for interactions of this agent, its use represents an acceptable clinical decision. Still, DDIs can be significant in certain clinical situations and a careful evaluation is always needed when prescribing NOACs.
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Affiliation(s)
- Alberto Corsini
- Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy.,Multimedica IRCCS, Milan, Italy
| | - Nicola Ferri
- Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy
| | - Marco Proietti
- Department of Clinical Sciences and Community Health, University of Milan, Via della Commenda 19, 20122, Milan, Italy. .,Geriatric Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. .,Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK.
| | - Giuseppe Boriani
- Cardiology Division, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Policlinico di Modena, Modena, Italy
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43
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Briggler R, Matherne E, Johnson C, Boehmer K. Recurrent Thrombi in an Obese Patient With History of Bariatric Surgery Despite Anti-Xa Therapy. J Pharm Pract 2021; 35:811-816. [PMID: 33827312 DOI: 10.1177/08971900211004837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Obesity and gastric bypass surgery can complicate anticoagulation therapy. In general, patients post-bariatric surgery are considered to be at a moderate risk for deep venous thromboembolism or pulmonary embolism. American Association of Clinical Endocrinologists/American College of Endocrinology, The Obesity Society, American Society for Metabolic & Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists guidelines recommend chemical prophylaxis with unfractionated heparin or low molecular weight heparin after surgery until the patient is fully mobile, and for those who require chronic anticoagulation, the International Society of Thrombosis and Haemostasis recommend warfarin if body mass index (BMI) is above 40 kg/m2 or weight is more than 120 kg. Clinical decision making regarding anticoagulation in the following patient case is complicated by multiple factors, most notably the combination of obesity and history of gastric bypass surgery. This patient failed multiple anticoagulation regimens, with apixaban and rivaroxaban therapies each ending in venous thromboemboli and warfarin leading to subtherapeutic International Normalized Ratio (INR)s despite dose adjustment. However, she is currently therapeutic on the combination of enoxaparin and warfarin as shown by INR and anti-Xa level monitoring. In this case and similar instances, there could be a need for anticoagulant dose adjustments, different INR goals, or a combination of different anticoagulants. Providers should take an individualized approach to patients who have had bariatric surgery with elevated BMI as a key factor in anticoagulant selection.
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Affiliation(s)
- Rachel Briggler
- 15499University of Arkansas for Medical Sciences College of Pharmacy, Little Rock, AR, USA
| | - Emma Matherne
- 15499University of Arkansas for Medical Sciences College of Pharmacy, Little Rock, AR, USA
| | - Chris Johnson
- Pharmacy Practice, 15499University of Arkansas for Medical Sciences College of Pharmacy, Little Rock, AR, USA
| | - Kaci Boehmer
- Pharmacy Practice, 15499University of Arkansas for Medical Sciences College of Pharmacy, Little Rock, AR, USA
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44
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Hong J, Ahn SY, Lee YJ, Lee JH, Han JW, Kim KH, Yhim HY, Nam SH, Kim HJ, Song J, Kim SH, Bang SM, Kim JS, Mun YC, Bae SH, Kim HK, Jang S, Park R, Choi HS, Kim I, Oh D. Updated recommendations for the treatment of venous thromboembolism. Blood Res 2021; 56:6-16. [PMID: 33627521 PMCID: PMC7987480 DOI: 10.5045/br.2021.2020083] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 01/06/2021] [Accepted: 01/06/2021] [Indexed: 12/13/2022] Open
Abstract
Venous thromboembolism (VTE), which includes pulmonary embolism and deep vein thrombosis, is a condition characterized by abnormal blood clot formation in the pulmonary arteries and the deep venous vasculature. It is often serious and sometimes even fatal if not promptly and appropriately treated. Moreover, the later consequences of VTE may result in reduced quality of life. The treatment of VTE depends on various factors, including the type, cause, and patient comorbidities. Furthermore, bleeding may occur as a side effect of VTE treatment. Thus, it is necessary to carefully weigh the benefits versus the risks of VTE treatment and to actively monitor patients undergoing treatment. Asian populations are known to have lower VTE incidences than Western populations, but recent studies have shown an increase in the incidence of VTE in Asia. A variety of treatment options are currently available owing to the introduction of direct oral anticoagulants. The current VTE treatment recommendation is based on evidence from previous studies, but it should be applied with careful consideration of the racial, genetic, and social characteristics in the Korean population.
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Affiliation(s)
- Junshik Hong
- Division of Hematology-Medical Oncology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Department of Hematology-Oncology, Korea
| | - Seo-Yeon Ahn
- Chonnam National University Hwasun Hospital, Hwasun, Korea
| | - Yoo Jin Lee
- Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Ji Hyun Lee
- Division of Hematology and Oncology, Department of Internal Medicine, Dong-A University College of Medicine, Dong-A University Hospital, Busan, Korea
| | - Jung Woo Han
- Division of Pediatric Hematology and Oncology, Department of Pediatrics, Yonsei University College of Medicine, Yonsei University Health System, Jeonju, Korea
| | - Kyoung Ha Kim
- Department of Oncology and Hematology, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Department of Internal Medicine, Jeonju, Korea
| | - Ho-Young Yhim
- Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
| | | | - Hee-Jin Kim
- Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jaewoo Song
- Department of Laboratory Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea
| | - Sung-Hyun Kim
- Division of Hematology and Oncology, Department of Internal Medicine, Dong-A University College of Medicine, Dong-A University Hospital, Busan, Korea
| | - Soo-Mee Bang
- Division of Hematology-Medical Oncology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jin Seok Kim
- Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Department of Internal Medicine, Seoul, Korea
| | - Yeung-Chul Mun
- Ewha Womans University College of Medicine, Seoul, Korea
| | - Sung Hwa Bae
- Daegu Catholic University School of Medicine, Daegu Catholic University Hospital, Daegu, Department of Laboratory Medicine, Korea
| | - Hyun Kyung Kim
- Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Seongsoo Jang
- University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Rojin Park
- Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Hyoung Soo Choi
- Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Inho Kim
- Division of Hematology-Medical Oncology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Department of Hematology-Oncology, Korea
| | - Doyeun Oh
- Division of Hematology-Oncology, Department of Internal Medicine, CHA University School of Medicine, Seongnam, Korea
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45
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Nasser MF, Khaled Z, Jabri A, Karim S. The importance of use of appropriate anticoagulant in atrial fibrillation after gastric bypass surgery. HeartRhythm Case Rep 2021; 7:354-356. [PMID: 34194978 PMCID: PMC8226277 DOI: 10.1016/j.hrcr.2021.03.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Mohamed Farhan Nasser
- Heart and Vascular Institute, MetroHealth Medical Center / Case Western Reserve University, Cleveland, Ohio
| | - Zahra Khaled
- Heart and Vascular Institute, MetroHealth Medical Center / Case Western Reserve University, Cleveland, Ohio
| | - Ahmad Jabri
- Heart and Vascular Institute, MetroHealth Medical Center / Case Western Reserve University, Cleveland, Ohio
| | - Saima Karim
- Heart and Vascular Institute, MetroHealth Medical Center / Case Western Reserve University, Cleveland, Ohio
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46
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Wadsworth D, Sullivan E, Jacky T, Sprague T, Feinman H, Kim J. A review of indications and comorbidities in which warfarin may be the preferred oral anticoagulant. J Clin Pharm Ther 2021; 46:560-570. [PMID: 33393699 DOI: 10.1111/jcpt.13343] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 12/16/2020] [Indexed: 02/06/2023]
Abstract
WHAT IS KNOWN AND OBJECTIVE Direct oral anticoagulants (DOACs) are increasingly prescribed instead of warfarin for chronic anticoagulation for ease of dosing, fewer interactions, and less stringent monitoring. However, it is important to consider indications and comorbidities for which warfarin is still the preferred anticoagulant. This review aims to capture these clinical scenarios in which warfarin may still be preferred over DOACs. METHODS We undertook a comprehensive literature search using the PubMed database. Key search terms were based on DOAC clinical trial exclusion criteria, as well as indications and conditions in which the use of DOACs for anticoagulation has suggested harm. Society guidelines and tertiary literature were used to inform expert opinion where necessary. Studies were included if they investigated the use of DOACs or warfarin in the identified indications or conditions. RESULTS AND DISCUSSION Currently, evidence for the use of warfarin over DOACs for anticoagulation is strongest for patients with prosthetic valves, antiphospholipid syndrome, or a high risk of gastrointestinal bleeding. For several clinical situations, including mitral stenosis, obesity, altered gastrointestinal anatomy, pulmonary arterial hypertension, renal or hepatic impairment, and left ventricular thrombus, evidence is lacking but may eventually support the use of DOACs. Depending on indication and condition, appropriateness of DOAC use may vary by agent. WHAT IS NEW AND CONCLUSION New evidence continues to support new indications and conditions in which DOACs may be appropriate to use for anticoagulation. There are key clinical scenarios, however, in which emerging literature continues to support warfarin as the preferred anticoagulant.
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Affiliation(s)
- Daniel Wadsworth
- The University of North Carolina Eshelman School of Pharmacy, Chapel Hill, NC, USA
| | - Emma Sullivan
- The University of North Carolina Eshelman School of Pharmacy, Chapel Hill, NC, USA
| | - Thomas Jacky
- The University of North Carolina Eshelman School of Pharmacy, Chapel Hill, NC, USA
| | - Taylor Sprague
- The University of North Carolina Eshelman School of Pharmacy, Chapel Hill, NC, USA
| | - Hannah Feinman
- The University of North Carolina Eshelman School of Pharmacy, Chapel Hill, NC, USA
| | - Jennifer Kim
- Cone Health Department of Internal Medicine, Greensboro, NC, USA
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Iida H, Miyake T, Tani M, Tanaka T, Kawakami K, Ikuno Y, Mandai R, Shimizu T. Cerebellar hemorrhage in patients treated with edoxaban for portal vein thrombosis after hepatobiliary surgery: a report of two cases. Surg Case Rep 2020; 6:319. [PMID: 33305345 PMCID: PMC7728984 DOI: 10.1186/s40792-020-01086-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 11/30/2020] [Indexed: 12/31/2022] Open
Abstract
Background The standard therapeutic agent administered for portal vein thrombosis (PVT) in patients with or without cirrhosis is warfarin or low-molecular weight heparin. However, therapy with edoxaban appears to be one of the most promising treatments for patients who require anticoagulation therapy. We encountered two cases of cerebellar hemorrhage in patients treated with edoxaban for PVT after hepatobiliary surgery during the past 2 years. Case presentation Case 1 A 67-year-old male underwent cholecystectomy and choledocholithotomy with choledochoduodenostomy to treat choledocholithiasis after cholangitis. Enhanced computed tomography (CT) on the 1st postoperative day (POD) revealed thrombosis in the left and anterior segment of the portal vein branches. We administered antithrombin III concentrate with heparin for 5 days; thereafter, we switched to 60 mg edoxaban. A sudden decrease in the patient’s level of consciousness was observed due to cerebellar hemorrhage on POD 27. Cerebellar hemorrhage was successfully treated with craniotomy hematoma evacuation and ventricular drainage; however, the patient died from aggravation of hepatic failure due to PVT and intra-abdominal infection. Case 2 A 67-year-old male received laparoscopic microwave coagulation therapy for two hepatic nodules suggestive of hepatocellular carcinoma in the left lobe of the liver due to alcoholic hepatitis. Enhanced CT on POD 5 revealed a thrombosis in the 4th segment branch of the portal vein, and the patient was treated with 60 mg edoxaban. Cerebellar hemorrhage with ventricular perforation occurred on POD 15. Cerebellar hemorrhage was successfully treated by craniotomy hematoma evacuation with ventricular drainage. Prolonged consciousness disorder persisted, and the patient was transferred to another medical facility for rehabilitation 49 days after brain surgery. Conclusions Although edoxaban is recently described to be one of the options for patients with PVT who require anticoagulation therapy instead of heparin or warfarin, it should be used with caution, given its propensity to induce severe hemorrhagic adverse events in cases such as those described above. The monitoring of hepatic dysfunction and decision for continuation of drug may be required during edoxaban use for PVT, especially after hepatobiliary surgery.
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Affiliation(s)
- Hiroya Iida
- Department of Surgery, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan
| | - Toru Miyake
- Department of Surgery, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan
| | - Masaji Tani
- Department of Surgery, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan
| | - Takuya Tanaka
- Medical Safety Section, Shiga University of Medical Science Hospital, Otsu, Shiga, 520-2192, Japan
| | - Kayo Kawakami
- Medical Safety Section, Shiga University of Medical Science Hospital, Otsu, Shiga, 520-2192, Japan
| | - Yoshihiro Ikuno
- Medical Safety Section, Shiga University of Medical Science Hospital, Otsu, Shiga, 520-2192, Japan
| | - Ryoichi Mandai
- Medical Safety Section, Shiga University of Medical Science Hospital, Otsu, Shiga, 520-2192, Japan
| | - Tomoharu Shimizu
- Medical Safety Section, Shiga University of Medical Science Hospital, Otsu, Shiga, 520-2192, Japan.
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48
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Streiff MB, Abutalib SA, Farge D, Murphy M, Connors JM, Piazza G. Update on Guidelines for the Management of Cancer-Associated Thrombosis. Oncologist 2020; 26:e24-e40. [PMID: 33275332 DOI: 10.1002/onco.13596] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Accepted: 11/10/2020] [Indexed: 12/21/2022] Open
Abstract
Cancer-associated thrombosis (CAT) is a major cause of morbidity and mortality in patients with cancer. Over the past 2 decades, enormous advances have been made in the management of CAT. The growing evidence base informing practice has led to the publication of a number of guidelines and guidance documents on the diagnosis and treatment of CAT. The goal of this review is to examine the latest versions of evidence-based guidelines, highlighting the differences and similarities in their methodology, their disease-specific content, and recommendations for management. Our analysis shows that for most clinical topics, the different guidelines provide roughly similar management advice. However, there are a number of important clinical topics in CAT that are not currently covered by the existing guidelines. We think inclusion of these topics in future versions of the guidelines will facilitate ongoing efforts to optimize the care of patients with CAT. IMPLICATIONS FOR PRACTICE: Cancer-associated thrombosis (CAT) is a common complication in patients with cancer. This review examines the differences and similarities of the current CAT guidelines methods and recommendations. Current guidelines largely agree on many aspects of CAT management. However, there are a number of topics in CAT that are not currently included in guidelines where evidence-based guidance would be very helpful for clinicians. Coverage of these topics in future guidelines is encouraged to optimize clinical practice.
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Affiliation(s)
- Michael B Streiff
- Division of Hematology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | | | - Dominique Farge
- Unité de Médecine Interne: Maladies Auto-immunes et Pathologie Vasculaire (UF 04), Université de Paris, IRSL, Recherche clinique appliquée à l'hématologie, Paris, France.,Department of Medicine, McGill University Health Center, Montreal, Canada
| | - Martina Murphy
- Division of Hematology/Oncology, University of Florida, Gainesville, Florida, USA
| | - Jean M Connors
- Harvard Medical School, Boston, Massachusetts, USA.,Cardiovascular Medicine Division at the Brigham and Women's Hospital, Boston, Massachusetts, USA.,Brigham and Womens Hospital and Dana-Farber Cancer Institute, Boston Massachusetts, USA
| | - Gregory Piazza
- Harvard Medical School, Boston, Massachusetts, USA.,Cardiovascular Medicine Division at the Brigham and Women's Hospital, Boston, Massachusetts, USA.,Division of Hematology/Oncology, University of Florida, Gainesville, Florida, USA
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49
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Hendricks AK, Zieminski JJ, Yao X, Dunlay SM, Sangaralingham LR, O'Meara JG, Herrin TR, Nei SD. Safety and Efficacy of Oral Anticoagulants for Atrial Fibrillation in Patients After Bariatric Surgery. Am J Cardiol 2020; 136:76-80. [PMID: 32941819 DOI: 10.1016/j.amjcard.2020.09.020] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 09/04/2020] [Accepted: 09/09/2020] [Indexed: 12/14/2022]
Abstract
Anticoagulation management is challenging in bariatric surgery patients, due to altered gastrointestinal anatomy and potentially reduced absorption. Few studies have evaluated clinical outcomes in this population. The objective of this study was to compare the efficacy and safety of oral anticoagulants in patients with and without a history of bariatric surgery. A retrospective, matched cohort study was conducted, utilizing data from the OptumLabs Data Warehouse. Patients ≥18 years old, with nonvalvular atrial fibrillation (NVAF), and treated with an oral anticoagulant between January 1, 2010 and December 31, 2018 were included. Outcomes were compared between bariatric and nonbariatric surgery patients. Secondary analysis compared warfarin to the direct oral anticoagulants (DOAC) in the bariatric cohort. The primary efficacy outcome was the rate of ischemic stroke and systemic embolism and the primary safety outcome was major bleeding. A total of 1,673 bariatric surgery and 155,619 nonbariatric surgery patients were identified. There was no significant difference in the rate of ischemic stroke or systemic embolism (0.83 vs 1.32 per 100 person years; Hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.31 to 1.22; p = 0.17) or major bleeding (5.30 vs 4.87 per 100 person years; HR 1.05, 95% CI 0.80 to 1.37; p = 0.73) between bariatric and nonbariatric surgery patients. In bariatric surgery patients alone, efficacy and safety were similar with warfarin compared with the DOACs. Results of this study suggest that bariatric surgery patients are not at an increased thrombotic or bleeding risk when using oral anticoagulants for NVAF. DOACs may be a reasonable alternative to warfarin.
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Affiliation(s)
- Abby K Hendricks
- Department of Pharmacy, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905.
| | - Joseph J Zieminski
- Department of Pharmacy, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905
| | - Xiaoxi Yao
- Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota; Division of Health Care Policy and Research, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
| | - Shannon M Dunlay
- Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota; Division of Health Care Policy and Research, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota
| | - Lindsey R Sangaralingham
- Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota; Optum Labs, Cambridge, Minnesota
| | - John G O'Meara
- Department of Pharmacy, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905
| | - Theocles R Herrin
- Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota; Optum Labs, Cambridge, Minnesota
| | - Scott D Nei
- Department of Pharmacy, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905
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50
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Gressel GM, Marcus JZ, Mullen MM, Sinno AK. Direct oral anticoagulant use in gynecologic oncology: A Society of Gynecologic Oncology Clinical Practice Statement. Gynecol Oncol 2020; 160:312-321. [PMID: 33257014 DOI: 10.1016/j.ygyno.2020.11.020] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 11/17/2020] [Indexed: 12/20/2022]
Abstract
Venous thromboembolism (VTE) is a common cause of morbidity and mortality in women with gynecologic malignancies. This practice statement provides clinical data and overall quality of evidence regarding the use of direct oral anticoagulants (DOACs) in this patient population. Specifically, it reviews patient selection, safety measures, and nuances of perioperative use of these medications. The scope of this document is limited to DOAC use in gynecologic oncology rather than a broad discussion of VTE prophylaxis and management in general. The following recommendations and examination of extant data are based on DOAC trials conducted primarily in mixed populations with different cancer subtypes. Many of these trials include few, or no, women with gynecologic cancer. However, because there is very limited data in gynecologic cancer-specific populations, the results of these studies represent the best available evidence to support treatment recommendations in our patients. The members of the Society of Gynecologic Oncology (SGO) Clinical Practice Committee believe that the results of these studies may be extrapolated, with caution, to VTE treatment and prophylaxis for patients with gynecologic cancer.
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Affiliation(s)
- Gregory M Gressel
- Division of Gynecologic Oncology, Department of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, United States of America.
| | - Jenna Z Marcus
- Division of Gynecologic Oncology, Department of Obstetrics & Gynecology and Reproductive Health, Rutgers New Jersey Medical School, Newark, NJ, United States of America
| | - Mary M Mullen
- Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, Washington University School of Medicine, St. Louis, MO, United States of America
| | - Abdulrahman K Sinno
- Division of Gynecologic Oncology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, United States of America
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