Anticoagulation Therapy Joe F Lau Geoffrey D Barnes Michael B Streiff Editors 123 Anticoagulation Therapy Joe F Lau • Geoffrey D Barnes Michael B Streiff Editors Anticoagulation Therapy Editors Joe F Lau, MD, PhD Associate Professor of Cardiology Department of Cardiology Zucker School of Medicine at Hofstra/Northwell Northwell Health Manhasset, NY, USA Geoffrey D Barnes, MD, MSc Assistant Professor Division of Internal Medicine Frankel Cardiovascular Center at the University of Michigan Ann Arbor, MI, USA Michael B Streiff, MD Professor of Medicine and Pathology Division of Hematology Department of Medicine The Johns Hopkins University School of Medicine Baltimore, MD, USA ISBN 978-3-319-73708-9 ISBN 978-3-319-73709-6 https://doi.org/10.1007/978-3-319-73709-6 (eBook) Library of Congress Control Number: 2018935389 © Springer International Publishing AG, part of Springer Nature 2018 This work is subject to copyright All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed The use of general descriptive names, registered names, trademarks, service marks, etc in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Printed on acid-free paper This Springer imprint is published by the registered company Springer International Publishing AG part of Springer Nature The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Preface Since the introduction of vitamin K antagonists in the 1950s, the field of anticoagulation has evolved considerably to include an ever-increasing number of new therapeutic agents and procedures for thromboembolic disease The rapidity of change presents a challenge for busy healthcare providers to stay abreast of the latest developments in the management of thrombotic disease This book outlines the current state of antithrombotic therapy which will serve as a foundation upon which the field will inevitably continue to grow and develop We hope that the readers will find this book to be a valuable resource and reliable reference for patient care Manhasset, NY, USA Ann Arbor, MI, USA Baltimore, MD, USA Joe F Lau, MD, PhD Geoffrey D Barnes, MD, MSc Michael B Streiff, MD v Acknowledgments For my parents, who sacrificed and gave their all so their children can succeed; for my wife, Nora, and my sons, Justin and Daniel, who have continued to inspire me through their unwavering and loving support; and to my mentors and colleagues over the years—I thank you for keeping doors open for the kid who dreamed big.—Joe F Lau For my parents, who nurtured my love of science and medicine; for my husband, Grant, and my daughter, Gillian, who give me endless support and encouragement; and to my mentors, colleagues, and patients who have taught me the true joy of medicine.—Geoffrey D Barnes I would like to acknowledge my wife, Lauren, and my children, Zachary and Madeline, who have been a source of pride and joy and who have been unbelievably supportive despite my crazy schedule and extremely patient and tolerant of my working vacations and weekends I would also like to thank my parents, Richard and Jenny Streiff, as well as the mentors who taught and inspired me including Richard R Streiff, MD; Craig S Kitchens, MD; Richard Lottenberg, MD; William R Bell, MD, PhD; Jerry L Spivak, MD; and Thomas S Kickler, MD.—Michael B Streiff vii Contents Introduction Joe F Lau, Geoffrey D Barnes, and Michael B Streiff Part I Anticoagulants Warfarin Gregory C Hadlock, Allison E Burnett, and Edith A Nutescu Unfractionated Heparin and Low-Molecular-Weight Heparin Rhynn J Malloy, Jessica Rimsans, Megan Rhoten, Katelyn Sylvester, and John Fanikos Parenteral Anticoagulants: Direct Thrombin Inhibitors and Pentasaccharides Meghan L Fletcher and Allison E Burnett 31 59 Direct Oral Anticoagulants Natalie S Evans Anticoagulation Reversal 105 Deborah Hornacek and Marcelo P V Gomes Transitioning Between Anticoagulants 133 Maya Serhal and Marcelo P V Gomes Part II 87 Clinical Applications of Anticoagulant Therapy The Anticoagulation Clinic 153 Nathan P Clark and Daniel M Witt Perioperative Management of Anticoagulants 175 Ibrahim M Ali, Alexander Volodarskiy, and Joe F Lau 10 Acute Coronary Syndromes 197 Nilay K Patel and Sammy Elmariah 11 Antithrombotic Therapy for Patients with Atrial Fibrillation 217 Kyla M Lara and Jonathan L Halperin ix Contents x 12 Anticoagulant Strategies for Electrophysiology Procedures 239 Stuart J Beldner and David L Stern 13 Anticoagulation for Cardiac Prosthetic Devices: Prosthetic Heart Valves, Left Ventricular Assist Devices, and Septal Closure Devices 253 Matthew T Crim, Supriya Shore, Suegene K Lee, and Bryan J Wells 14 Anticoagulation in Venous Thromboembolism 297 Geoffrey D Barnes and Elizabeth T Renner 15 Thrombophilic States 325 Adriana Guigova and Tony Philip 16 Thrombophilia Testing 345 Teresa L Carman 17 Heparin-Induced Thrombocytopenia 359 Emily Downs, Svetlana Goldman, Surabhi Palkimas, and Aditya M Sharma 18 Anticoagulation Therapy in Pregnant Patients 391 Steven A Savella, Jessica A Kvasic, and Joe F Lau 19 Anticoagulation in the Elderly 409 Ruchika Harisingani, Ibrahim M Ali, Bhakti Shah, and Salonie Pereira 20 Anticoagulation in the Patient with Cancer 425 Simon Mantha, Dipti Gupta, Chadi Salmane, Mansour Khaddr, Gerald A Soff, and Richard Steingart Index 441 Contributors Ibrahim M Ali Department of Cardiology, Northwell Health, Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USA Geoffrey D Barnes Department of Internal Medicine, Division of Cardiovascular Medicine, Frankel Cardiovascular Center at the University of Michigan, Ann Arbor, MI, USA Stuart J Beldner Department of Cardiology, Northwell Health, Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USA Allison E Burnett University of New Mexico College of Pharmacy, Albuquerque, NM, USA Teresa L Carman Division of Cardiovascular Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, USA Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA Nathan P Clark Clinical Pharmacy Anticoagulation and Anemia Service, Kaiser Permanente Colorado, Aurora, CO, USA Matthew T Crim Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA Emily Downs Department of Surgery, Division of Thoracic and Cardiovascular Surgery, University of Virginia Medical Center, University of Virginia, Charlottesville, VA, USA Sammy Elmariah Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA Natalie S Evans Department of Cardiovascular Medicine, Section of Vascular Medicine, Cleveland Clinic, Cleveland, OH, USA John Fanikos Department of Pharmacy, Brigham and Women’s Hospital, Boston, MA, USA Meghan L Fletcher Inpatient Pharmacy Department, University of New Mexico Hospital, Albuquerque, NM, USA Svetlana Goldman Department of Pharmacy, University of Virginia Medical Center, University of Virginia, Charlottesville, VA, USA xi xii Marcelo P V Gomes Department of Cardiovascular Medicine, Section of Vascular Medicine, Cleveland Clinic, Cleveland, OH, USA Adriana Guigova Division of Hematology/Oncology, Department of Medicine, Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Lake Success, NY, USA Dipti Gupta Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA Gregory C Hadlock Inpatient Pharmacy Department, University of New Mexico Hospital, Albuquerque, NM, USA Jonathan L Halperin The Cardiovascular Institute, Mount Sinai Medical Center, New York, NY, USA Ruchika Harisingani Department of Medicine, Northwell Health, Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USA Deborah Hornacek Department of Cardiovascular Medicine, Section of Vascular Medicine, Cleveland Clinic, Cleveland, OH, USA Mansour Khaddr Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA Jessica A Kvasic Department of Medicine, Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Manhasset, NY, USA Kyla M Lara Department of Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY, USA Joe F Lau Department of Cardiology, Zucker School of Medicine at Hofstra/ Northwell, Northwell Health, Manhasset, NY, USA Suegene K Lee Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA Rhynn J Malloy Department of Pharmacy, Brigham and Women’s Hospital, Boston, MA, USA Simon Mantha Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA Edith A Nutescu Department of Pharmacy Systems, Outcomes and Policy, Center for Pharmacoepidemiology and Pharmacoeconomic Research, The University of Illinois at Chicago College of Pharmacy, Chicago, IL, USA Surabhi Palkimas Department of Pharmacy, University of Virginia Medical Center, University of Virginia, Charlottesville, VA, USA Nilay K Patel Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA Salonie Pereira Department of Medicine, Northwell Health, Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USA Contributors S Mantha et al 438 30 Streiff MB.  Cancer-associated venous thromboembolic disease, version 1.2016 of NCCN Guidelines 2016 Available from: www.nccn.org 31 Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, et al Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines Chest 2012;141(2 Suppl):e419S–94S 32 Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, et  al Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report Chest 2016;149(2):315–52 33 Deng K, Parameswaran R, Soff BP, Soff GA.  Incidental versus symptomatic pulmonary embolism in cancer patients: a multivariate analysis of recurrent VTE and mortality (abstract) Blood 2012;120:2257 34 Akl EA, Kahale L, Barba M, Neumann I, Labedi N, Terrenato I, et  al Anticoagulation for the longterm treatment of venous thromboembolism in patients with cancer Cochrane Database Syst Rev 2014;7:CD006650 35 Carrier M, Le Gal G, Cho R, Tierney S, Rodger M, Lee AY.  Dose escalation of low molecular weight heparin to manage recurrent venous thromboembolic events despite systemic anticoagulation in cancer patients J Thromb Haemost 2009;7(5):760–5 36 Prandoni P, Lensing AW, Piccioli A, Bernardi E, Simioni P, Girolami B, et al Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis Blood 2002;100(10):3484–8 37 van Doormaal FF, Raskob GE, Davidson BL, Decousus H, Gallus A, Lensing AW, Piovella F, Prins MH, Büller HR. Treatment of venous thromboembolism in patients with cancer: subgroup analysis of the Matisse clinical trials Thromb Haemost 2009;101(4):762–9 38 NIH.  Cancer associated thrombosis, a pilot treatment study using rivaroxaban (CASTA-DIVA) NCT02746185 Available from: www.clinicaltrials gov 39 NIH. Apixaban or dalteparin in reducing blood clots in patients with cancer related venous thromboembolism NCT02585713 40 van Es N, Di Nisio M, Bleker SM, Segers A, Mercuri MF, Schwocho L, et al Edoxaban for treatment of venous thromboembolism in patients with cancer Rationale and design of the Hokusai VTE-cancer study Thromb Haemost 2015;114(6):1268–76 41 Schulman S, Goldhaber SZ, Kearon C, Kakkar AK, Schellong S, Eriksson H, et  al Treatment with dabigatran or warfarin in patients with venous thromboembolism and cancer Thromb Haemost 2015;114(1):150–7 42 Prins MH, Lensing AW, Bauersachs R, van Bellen B, Bounameaux H, Brighton TA, et al Oral rivaroxaban versus standard therapy for the treatment of symp- 43 44 45 46 47 48 49 50 51 52 53 54 tomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies Thromb J. 2013;11(1):21 Raskob GE, van Es N, Segers A, Angchaisuksiri P, Oh D, Boda Z, et  al Edoxaban for venous thromboembolism in patients with cancer: results from a non-inferiority subgroup analysis of the HokusaiVTE randomised, double-blind, double-dummy trial Lancet Haematol 2016;3(8):e379–87 Bott-Kitslaar DM, Saadiq RA, McBane RD, Loprinzi CL, Ashrani AA, Ransone TR, et  al Efficacy and safety of rivaroxaban in patients with venous thromboembolism and active malignancy: a single-center registry Am J Med 2016;129(6):615–9 Mantha S, Laube E, Miao Y, Sarasohn DM, Parameswaran R, Stefanik S, et  al Safe and effective use of rivaroxaban for treatment of cancerassociated venous thromboembolic disease: a prospective cohort study J  Thromb Thrombolysis 2017;43(2):166–71 Cambareri C, Yao X, Merl MY, Pham T, Lee AI. The use of oral anticoagulants for the treatment of venous thromboembolism in cancer patients (abstract) Blood 2015;126:4728 Chaudhury A, Balakrishnan A, Thai C, Holmstrom B, Jaglal MV. Evaluation of rivaroxaban and dalteparin in cancer associated thrombosis (abstract) Blood 2015;126:432 Win KZ, Wilson N, Stenehjem DD, Tanner N, Rodgers GM, Gilreath J. Effectiveness and safety of rivaroxaban in treatment of venous thromboembolism in cancer patients (abstract) Blood 2015;126:2319 Vedovati MC, Germini F, Agnelli G, Becattini C.  Direct oral anticoagulants in patients with VTE and cancer: a systematic review and meta-analysis Chest 2015;147(2):475–83 Sherwood MW, Nessel CC, Hellkamp AS, Mahaffey KW, Piccini JP, Suh EY, et al Gastrointestinal bleeding in patients with atrial fibrillation treated with rivaroxaban or warfarin: ROCKET AF trial J  Am Coll Cardiol 2015;66(21):2271–81 Goodman SG, Wojdyla DM, Piccini JP, White HD, Paolini JF, Nessel CC, et al Factors associated with major bleeding events: insights from the ROCKET AF trial (rivaroxaban once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation) J Am Coll Cardiol 2014;63(9):891–900 Posch F, Konigsbrugge O, Zielinski C, Pabinger I, Ay C.  Treatment of venous thromboembolism in patients with cancer: a network meta-analysis comparing efficacy and safety of anticoagulants Thromb Res 2015;136(3):582–9 Agnelli G, Bolis G, Capussotti L, Scarpa RM, Tonelli F, Bonizzoni E, et  al A clinical outcomebased prospective study on venous thromboembolism after cancer surgery: the @RISTOS project Ann Surg 2006;243(1):89–95 Agnelli G, George DJ, Kakkar AK, Fisher W, Lassen MR, Mismetti P, et al Semuloparin for thrombopro- 20 Anticoagulation in the Patient with Cancer 55 56 57 58 59 60 61 62 63 64 65 phylaxis in patients receiving chemotherapy for cancer N Engl J Med 2012;366(7):601–9 Maraveyas A, Waters J, Roy R, Fyfe D, Propper D, Lofts F, et al Gemcitabine versus gemcitabine plus dalteparin thromboprophylaxis in pancreatic cancer Eur J Cancer 2012;48(9):1283–92 Vadhan-Raj S, Zhou X, Varadhachary GR, Milind J, Fogelman D, Shroff R, et al Randomized controlled trial of dalteparin for primary thromboprophylaxis for venous thromboembolism (VTE) in patients with advanced pancreatic cancer (APC): risk factors predictive of VTE (abstract) Blood 2013;122:580 Zwicker JI, Liebman HA, Bauer KA, Caughey T, Campigotto F, Rosovsky R, et  al Prediction and prevention of thromboembolic events with enoxaparin in cancer patients with elevated tissue factorbearing microparticles: a randomized-controlled phase II trial (the Microtec study) Br J  Haematol 2013;160(4):530–7 Pelzer U, Opitz B, Deutschinoff G, Stauch M, Reitzig PC, Hahnfeld S, et  al Efficacy of prophylactic low-molecular weight heparin for ambulatory patients with advanced pancreatic cancer: outcomes from the CONKO-004 trial J Clin Oncol 2015;33(18):2028–34 Bach M, Bauersachs R.  Spotlight on advances in VTE management: CALLISTO and EINSTEIN CHOICE.  Thromb Haemost 2016;116(Suppl 2): S24–32 Palumbo A, Rajkumar SV, Dimopoulos MA, Richardson PG, San Miguel J, Barlogie B, et  al Prevention of thalidomide- and lenalidomideassociated thrombosis in myeloma Leukemia 2008; 22(2):414–23 Collins R, Scrimgeour A, Yusuf S, Peto R. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin Overview of results of randomized trials in general, orthopedic, and urologic surgery N Engl J Med 1988;318(18):1162–73 Nurmohamed MT, Rosendaal FR, Buller HR, Dekker E, Hommes DW, Vandenbroucke JP, et  al Low-molecular-weight heparin versus standard heparin in general and orthopaedic surgery: a metaanalysis Lancet 1992;340(8812):152–6 Akl EA, Terrenato I, Barba M, Sperati F, Sempos EV, Muti P, et  al Low-molecular-weight heparin vs unfractionated heparin for perioperative thromboprophylaxis in patients with cancer: a systematic review and meta-analysis Arch Intern Med 2008; 168(12):1261–9 Herishanu Y, Misgav M, Kirgner I, Ben-Tal O, Eldor A, Naparstek E.  Enoxaparin can be used safely in patients with severe thrombocytopenia due to intensive chemotherapy regimens Leuk Lymphoma 2004;45(7):1407–11 Ibrahim RB, Peres E, Dansey R, Abidi MH, Abella EM, Gumma MM, et  al Safety of low-dose lowmolecular-weight-heparins in thrombocytopenic stem cell transplantation patients: a case series and 439 66 67 68 69 70 71 72 73 74 75 76 77 78 review of the literature Bone Marrow Transplant 2005;35(11):1071–7 Mantha S, Miao Y, Wills J, Parameswaran R, Soff GA.  Enoxaparin dose reduction for thrombocytopenia in patients with cancer: a quality assessment study J Thromb Thrombolysis 2017;43(4):514–8 Garcia-Rodriguez LA, Gaist D, Morton J, Cookson C, Gonzalez-Perez A. Antithrombotic drugs and risk of hemorrhagic stroke in the general population Neurology 2013;81(6):566–74 Fang MC, Chang YC, Hylek EM, Rosand J, Greenberg SM, Go AS, et  al Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation Ann Intern Med 2004;141(10):745–52 Mandybur TI.  Intracranial hemorrhage caused by metastatic tumors Neurology 1977;27(7):650–5 Alvarado G, Noor R, Bassett R, Papadopoulos NE, Kim KB, Hwu WJ, et al Risk of intracranial hemorrhage with anticoagulation therapy in melanoma patients with brain metastases Melanoma Res 2012;22(4):310–5 Donato J, Campigotto F, Uhlmann EJ, Coletti E, Neuberg D, Weber GM, et  al Intracranial hemorrhage in patients with brain metastases treated with therapeutic enoxaparin: a matched cohort study Blood 2015;126(4):494–9 Mantia C, Uhlmann E, Puligandla M, Neuberg DS, Weber GM, Zwicker JI.  Intracranial hemorrhage in patients with primary brain tumors treated with therapeutic enoxaparin: a matched cohort study (abstract) Blood 2016;128:142 Boriani G, Pettorelli D.  Atrial fibrillation burden and atrial fibrillation type: clinical significance and impact on the risk of stroke and decision making for long-term anticoagulation Vasc Pharmacol 2016;83:26–35 Lee YJ, Park JK, Uhm JS, Kim JY, Pak HN, Lee MH, et al Bleeding risk and major adverse events in patients with cancer on oral anticoagulation therapy Int J Cardiol 2016;203:372–8 Farmakis D, Parissis J, Filippatos G.  Insights into onco-cardiologyatrial fibrillation in cancer J  Am Coll Cardiol 2014;63(10):945–53 Cheng WL, Kao YH, Chen SA, Chen YJ Pathophysiology of cancer therapy-provoked atrial fibrillation Int J Cardiol 2016;219:186–94 Zamorano JL, Lancellotti P, Rodriguez Munoz D, Aboyans V, Asteggiano R, Galderisi M, et al 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC) Eur Heart J. 2016;37(36):2768–801 Onaitis M, D’Amico T, Zhao Y, O’Brien S, Harpole D. Risk factors for atrial fibrillation after lung cancer surgery: analysis of the society of thoracic surgeons general thoracic surgery database Ann Thorac Surg 2010;90(2):368–74 S Mantha et al 440 79 Guzzetti S, Costantino G, Vernocchi A, Sada S, Fundaro C.  First diagnosis of colorectal or breast cancer and prevalence of atrial fibrillation Intern Emerg Med 2008;3(3):227–31 80 O’Neal WT, Lakoski SG, Qureshi W, Judd SE, Howard G, Howard VJ, et  al Relation Between Cancer and Atrial Fibrillation (from the REasons for Geographic And Racial Differences in Stroke Study) Am J Cardiol 2010;115(8):1090–4 81 Conen D, Wong JA, Sandhu RK, et al Risk of malignant cancer among women with new-onset atrial fibrillation JAMA Cardiol 2016;1(4):389–96 82 Melloni C, Shrader P, Carver J, Piccini J, Fonarow G, Ansell J, et  al Management and outcomes of patients with atrial fibrillation and cancer: The ORBIT-AF registry Eur Heart J  Qual Care Clin Outcomes 2017;3(3):192–7 83 Apostolakis S, Lane DA, Guo Y, Buller H, Lip GY.  Performance of the HEMORR(2)HAGES, ATRIA, and HAS-BLED bleeding risk-prediction scores in patients with atrial fibrillation undergoing anticoagulation: the AMADEUS (evaluating the use of SR34006 compared to warfarin or acenocoumarol in patients with atrial fibrillation) study J Am Coll Cardiol 2012;60(9):861–7 84 Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation JAMA 2001;285(22):2864–70 85 Hart RG, Pearce LA, Aguilar MI.  Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation Ann Intern Med 2007;146(12):857–67 86 Olesen JB, Sorensen R, Hansen ML, Lamberts M, Weeke P, Mikkelsen AP, et  al Non-vitamin K antagonist oral anticoagulation agents in anticoagulant naive atrial fibrillation patients: Danish nationwide descriptive data 2011-2013 Europace 2015;17(2):187–93 87 Steinberg B, Shrader P, Thomas L, Fonarow G, Hylek E, Ansell J, et al Oral anticoagulant selection in community patients with new-onset atrial fibrillation: results from the ORBIT-AF registry (abstract) J Am Coll Cardiol 2016;67(13_S):885 88 January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JJC, et al 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summarya report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society J Am Coll Cardiol 2014;64(21):2246–80 89 Larsen TB, Nielsen PB, Skjoth F, Rasmussen LH, Lip GY.  Non-vitamin K antagonist oral anticoagulants and the treatment of venous thromboembolism in cancer patients: a semi systematic review and meta-analysis of safety and efficacy outcomes PLoS One 2014;9(12):e114445 90 Laube ES, Yu A, Gupta D, Miao Y, Samedy P, Wills J, et al Rivaroxaban for stroke prevention in patients 91 92 93 94 95 96 97 98 99 100 101 102 103 104 with non-valvular atrial fibrillation and active cancer (abstract) Blood 2016;128:2621 Rooden CJ, Tesselaar ME, Osanto S, Rosendaal FR, Huisman MV. Deep vein thrombosis associated with central venous catheters - a review J Thromb Haemost 2005;3(11):2409–19 King MM, Rasnake MS, Rodriguez RG, Riley NJ, Stamm JA.  Peripherally inserted central venous catheter-associated thrombosis: retrospective analysis of clinical risk factors in adult patients South Med J. 2006;99(10):1073–7 Saber W, Moua T, Williams EC, Verso M, Agnelli G, Couban S, et  al Risk factors for catheterrelated thrombosis (CRT) in cancer patients: a patient-level data (IPD) meta-analysis of clinical trials and prospective studies J  Thromb Haemost 2011;9(2):312–9 O’Brien J, Paquet F, Lindsay R, Valenti D. Insertion of PICCs with minimum number of lumens reduces complications and costs J Am Coll Radiol 2013;10(11):864–8 Laube ES, Mantha S, Samedy P, Wills J, Harnicar S, Soff GA.  Treatment of central venous catheterassociated deep venous thrombosis in cancer patients with rivaroxaban Am J Hematol 2017;92(1):E9–E10 Lopez JA, Ross RS, Fishbein MC, Siegel RJ. Nonbacterial thrombotic endocarditis: a review Am Heart J. 1987;113(3):773–84 Deppisch LM, Fayemi AO.  Non-bacterial thrombotic endocarditis: clinicopathologic correlations Am Heart J. 1976;92(6):723–9 Gonzalez Quintela A, Candela MJ, Vidal C, Roman J, Aramburo P. Non-bacterial thrombotic endocarditis in cancer patients Acta Cardiol 1991;46(1):1–9 el-Shami K, Griffiths E, Streiff M.  Nonbacterial thrombotic endocarditis in cancer patients: pathogenesis, diagnosis, and treatment Oncologist 2007; 12(5):518–23 Dutta T, Karas MG, Segal AZ, Kizer JR.  Yield of transesophageal echocardiography for nonbacterial thrombotic endocarditis and other cardiac sources of embolism in cancer patients with cerebral ischemia Am J Cardiol 2006;97(6):894–8 Singhal AB, Topcuoglu MA, Buonanno FS.  Acute ischemic stroke patterns in infective and nonbacterial thrombotic endocarditis a diffusion-weighted magnetic resonance imaging study Stroke 2002; 33(5):1267–73 Sievers B, Brandts B, Franken U, Trappe H-J Cardiovascular magnetic resonance imaging demonstrates mitral valve endocarditis Am J  Med 2003;115(8):681–2 Schulte-Altedorneburg G, Nam E-M, Ritter M, Magyar T, Dittrich R, Csiba L, et al On the origin of microembolic signals J Neurol 2003;250(9):1044–9 Rogers LR, Cho ES, Kempin S, Posner JB. Cerebral infarction from non-bacterial thrombotic endocarditis Clinical and pathological study including the effects of anticoagulation Am J  Med 1987; 83(4):746–56 Index A Acquired thrombophilia APS, 332, 333 myeloproliferative neoplasms, 333–335 PNH, 335 Activated clotting time (ACT), 68, 69, 374 Activated partial thromboplastin time (aPTT), 98, 116, 134 anticoagulant response, 33 anti-Xa assays, 34, 36 argatroban and bivalirudin, 42 heparin resistant, 40 Activated protein C (APC), 396 Acute coronary syndromes (ACS), 31–35, 45, 48, 199, 202, 205–207 ACC and AHA, 198 anticoagulant medications, 199 antiplatelet therapy, 198 cardiac biomarkers, 197 clinical outcomes, 198 description, 197 DTI (see Direct thrombin inhibitors (DTI); Fondaparinux) LBBB, 197 LMWHs (see Low-molecular-weight heparins (LMWHs)) morbidity and mortality cause, 197 (see also Oral anticoagulant therapy) NSTE-ACS, 197 pathogenesis, 198, 199 pharmacologica/catheter-based reperfusion, 198 randomized controlled trials, 198 recommendations, 199, 200 revascularization, 198 STEMI, 77, 197 UA and NSTEMI, 77 UFH (see Unfractionated heparin (UFH)) Acute PE, thrombolysis, 299–301 Acute VTE management, anticoagulation therapy, 299 Adenosine diphosphate (ADP) receptor, 188 Adverse Event Reporting System (AERS) database, 115 American College of Cardiology (ACC), 164 American College of Cardiology/American Heart Association (ACC/AHA), 65, 259 American College of Chest Physicians (ACCP) guidelines, 259, 309, 369, 402, 413 American Society of Hematology (ASH), 346 Amplatzer Septal Occluder, 282–283 Anaphylactoid reactions, 109 Anaphylaxis, 109 Andexanet alfa (Portola), 117, 121, 122, 231 Anticoagulant effect (ACT), 65 Anticoagulant reversal, 97 Anticoagulants, 87 antiplatelet regimens, 176 decision-making process, 176, 177 DOACs (see Direct oral anticoagulants (DOACs)) surgical/invasive procedures, 176 Anticoagulant selection, 412, 413 Anticoagulation, 133, 297, 393 AHA/ACC guidelines, 402 bleeding, 21 cardioversion, 228 catheter ablation, 228–229 coronary artery disease, 229–230 effect, 231 elderly patients, 227 heart failure, 228 Hippocrates, initiation, 262–263 INR, 12 interruption and bridging, 263–265 patients education, 14 AF and prior stroke patients, 226 diabetes mellitus patients, 227 impaired renal function, patients, 226–227 pediatric patients, 25 pregnancy management (see Pregnancy) reversal, 231–232, 265 therapy, transition therapy (see Transition therapy) treatment, VTE (see Venous thromboembolism (VTE)) Anticoagulation bridging, 138, 142, 144, 145 Anticoagulation management service (AMS) areas of coordination, specialities, 155, 156 bleeding and thromboembolism, 165 care delivery sources, 154 © Springer International Publishing AG, part of Springer Nature 2018 J F Lau et al (eds.), Anticoagulation Therapy, https://doi.org/10.1007/978-3-319-73709-6 441 442 Anticoagulation management service (AMS) (cont.) clerical staff duties, 154 clinical leadership and operational management, 154 coding practices, 155 continuing education, 160 core competencies, providers, 160, 161 dabigatran and rivaroxaban prevalence, 168, 169 dashboards, 168 decision support and technology, 160 DOACs, 168 INR recall interval, 167 INR variability, 166 interventions, 168, 170 (see also Medication management) narrower target ranges, 167 NCBAP, 160 non-adherence with INR monitoring, 167 “no tamper zone”, 167 nurse- and pharmacy-led approaches, 156 optimized outpatient recommendations, 155, 157 outpatient structure, 155 panel-based structure, 159 POC testing, 156 providers, 155 PST and PSM, 156, 158 quality improvement measures, 165, 166 quality reporting, 168 structure, 154 “tampering”, 167 team-based structure, 159–160 telephone and in-office visits, 158, 159 therapeutic INR control, 165, 166 training program resources, 160, 162 VA and academic medical centers, 154 Anticoagulation therapy, 105, 278–279 See also Reversal strategies Antiphospholipid antibody syndrome (APS), 332, 333, 338, 393, 394 anionic phospholipids, 352 cystathionine β-synthase deficiency, 354 description, 352 ELISA, 353 fibrinolytic pathway, 353–354 homocysteine testing, 354 ISTH, 352 LA, ACA/β2GP-1 antibodies, 352 lupus anticoagulant presence, 353 MTHFR enzyme, 354 pregnancy-related placental issues, 353 Sapporo criteria, 352, 353 Antiplatelet agents, 187 aspirin (see Aspirin) primary and secondary prevention, 187 Antiplatelet therapy, 262, 279, 411 Antithrombin (AT), 32, 60, 61, 107, 326, 329, 330, 338 Antithrombotic therapy, 3, 105, 266–268, 277–278 Anti-Xa assays, 34, 121 Apixaban, 120, 121, 137, 143–145, 186, 304 DOACs, 212–214 oral factor Xa inhibitors, 223, 224 Index prevention stroke and systemic embolism, atrial fibrillation, 93–94 VTE, knee and hip arthroplasty, 94, 96 treatment and secondary prevention DVT, 94, 95 PE, 94, 95 Argatroban, 136, 142, 146, 374 ACT, 68 adverse effects, 70, 374 dosing, 66, 374 ECMO, 70 HIT, 63 INR, 69 PCI, 64, 65, 374 pediatric, 71 pregnancy, 71 warfarin, 381 Arterial thromboembolism (ATE), 1, 178, 180, 183, 184 Aspirin COX-1 and COX-2 inhibition, 187 extended VTE prophylaxis, 316–317 primary prevention, 187 secondary prevention discontinuation, 187 high and low bleeding risk procedure, 187–188 moderate bleeding risk procedure, 188 monotherapy, 187 Atherosclerosis intimal plaque development, arteries, 198 progression, 199 Atherosclerotic vascular disease, 99–100 Atrial fibrillation (AF), 12, 26, 88, 93, 94, 218–219, 242–244, 417–419, 432, 433 2014 ACC/AHA/HRS guidelines, 225 anticoagulation, 178 antithrombotic therapy, 225 catheter-based/surgical ablation procedures, 218 CHA2D2-VASc score, 178, 179 clinically significant cardiac arrhythmia, 217 clinical management, patients, 218 DOACs, 226 early cardioversion, 218 high thrombotic risk, 179 ineffective atrial contraction, 218 LAA, 218 lack of coordinated atrial contraction, 178 low thrombotic risk, 180 moderate thrombotic risk, 179–180 non-valvular (see Non-valvular atrial fibrillation) prevention of stroke and systemic embolism, 93, 94 promoters, triggers, substrate remodeling and sequelae, 218, 219 stroke risks among patients, 217 thromboembolism (see Thromboembolism) thrombotic risk stratification, patients, 179 Austrian Study of Recurrent Venous Thromboembolism (AUREC), 330 Index 443 B Bevacizumab, 337 Bioprosthetic heart valves, 98 antithrombotic therapy, 266–268 thrombosis risk, 265–266 Bivalirudin, 136, 142, 377, 378 ACT, 69 advantages, 376 adverse effects, 70 aPTT, 377 cardiac surgery, 379 data and clinical trials, 377, 378 dosing, 66, 376, 377 ECMO, 70 HIT, 64 INR, 69 NSTE-ACS, 205–206 PCI, 64, 65, 377, 379 pediatric, 71 pregnancy, 71 renal impairment, 377 STEMI, 206–207 Bleeding, 21–22 heart failure and diabetes, 411 life-/limb-threatening, 23, 24 non-major, 22 rates, 88 risk assessment tools, 414, 417 risk factors, 411 warfarin, 17 “Bridge” therapy, 96, 138–140, 183–185 BRUISE CONTROL trial, 242 occlusion devices, 255 valvular heart disease, 254 Cardiac surgery, 379 Cardiac thrombosis cell surface receptors, 255 device design, 256 embolism complications, 255 endothelial cells, 255 endothelialization process, 256 prosthetic materials, 255 tissue factor exposure/contact activation, 255 Cardiac valve, 14, 16, 20, 24, 27 Cardiomyopathy, 254–255 Cardioversion, 244–246 Catheter ablation, 228–229, 242–244 Catheter-associated VTE, 317 Center for Disease Control and Prevention (CDC), 298 Cerebral vein thrombosis, 317 CHA2DS2-VASc score, 178, 179, 190, 411, 412 Chromogenic factor X activity assay (CFX), 381 Ciraparantag, 117, 118, 122, 232 Cockcroft–Gault formula, 410 Cockcroft–Gault-estimated creatinine clearance (CG-CrCl), 88 Continuous renal replacement therapy (CRRT), 70 Coronary artery bypass grafting (CABG), 66 Coronary heart disease, 409, 410, 417 Coronary reperfusion, 64, 69 CRUSADE score, 209 Cutaneous manifestations, 364 C CABG, see Coronary artery bypass grafting (CABG) Cancer, 335 AF, 432, 433 anticoagulation bleeding risk, 426 prophylaxis, 431 DOACs, 429 fondaparinux, 428 LMWH, 431, 433 thrombocytopenia, 431 thrombotic and bleeding risk, 432 VTE recurrence, 426 warfarin, 433 Cancer-associated thrombosis (CAT) DOACs cohorts of patients, 430 primary/metastatic brain tumors, 432 vs VKA, 429 LMWH vs VKA, 428 pathophysiology, 426 γ-Carboxylation, 106 Cardiac prosthetic devices anatomy, 254 (see also Cardiac thrombosis) cardiomyopathy, 254–255 D Dabigatran, 87–90, 96–100, 137, 141, 143–145, 185–186, 210 Dabigatran-associated bleeding, 119 Dabigatran etexilate, 119, 222–223 Dalteparin, 43, 44, 46, 48–52 D-dimer test, 396 Deep vein thrombosis (DVT), 1, 88–92, 94, 95, 97, 120, 361, 391, 426 acute, 301 isolated distal DVT, 298 treatment apixaban, 94, 95 direct thrombin inhibitors, 88–90 edoxaban, 95, 97 rivaroxaban, 91, 92 Desirudin, 375, 376 Desmopressin acetate (DDAVP), 119 Dialysis, 379 Dilute Russell viper venom time (DRVVT), 352 Dilute thrombin time (dTT), 120 Direct factor Xa inhibitors apixaban, 93–96 edoxaban, 94–97 pharmacology, 90, 91 rivaroxaban, 90–93 444 Direct oral anticoagulants (DOACs), 3, 5, 12, 13, 26, 88, 98–100, 134, 176, 304, 400, 413 apixaban, 186, 212–214 bioprosthetic valves, 268–269 CAT, 430 characteristics, 210, 211 clinical case, 87 clinical characteristics, 309 dabigatran, 185–186, 210 (see also Dabigatran) description, 221 direct factor xa inhibitors (see Direct factor xa inhibitors) direct thrombin inhibitors (see Direct thrombin inhibitors (DTIs)) drug-drug interactions, 210 edoxaban, 186, 187 extended VTE treatment, 312–316 factor Xa inhibitors, 185 financial assistance mechanisms, 310 HIT, 382 and mechanical valves, 261–262 patient’s renal function, 185 perioperative management, 96–98 pharmacologic characteristics, 91 phase trials, stroke prevention, 222 populations atherosclerotic vascular disease, 99–100 bioprosthetic heart valves, 98 cancer, 98 mechanical heart valves, 98 obese patients, 99 prophylaxis, high-risk medical patients, 99 thrombophilia, 99 valvular atrial fibrillation, 98 prevention, cardioembolic stroke, 106 real-world experience, 96 rivaroxaban, 186, 210–212 safe use during pregnancy, 222 secondary prevention, 210 selection for AF, 230 transition therapy, 137, 138, 141 UFH, role of, 185 VTE treatment, 306, 428, 429 warfarin, 69, 144–145 Direct oral factor Xa inhibitors activated charcoal, 120 andexanet alfa, 121, 122 ANNEXA-4 study, 121 ANNEXA-A and ANNEXA-R trials, 121 anti-Xa activity, 121 apixaban, edoxaban and rivaroxaban, 120, 121 ciraparantag, 122 4-factor PCC, 120 gastrointestinal and intracranial bleeding, 121 preclinical animal and human blood, 121 rivaroxaban- and apixaban-treated patients, 121, 122 Direct thrombin inhibitors (DTIs), 3, 88–90, 134, 205–206, 349, 400 argatroban, 61 bivalent and univalent, 205 Index bivalirudin (see Bivalirudin) coagulation cascade activation, 205 HIT (see Heparin-induced thrombocytopenia (HIT)) non-valvular atrial fibrillation (see Non-valvular atrial fibrillation) oral, 119–120 parenteral, 119 pharmacokinetics absorption, 60 bivalirudin and argatroban, 60–62 distribution, 60 metabolism, 61 pharmacology, 60, 88 primary prophylaxis after hip replacement surgery, 89–90 transition therapy, 136 treatment and secondary prevention DVT, 88–90 PE, 88–90 Disseminated intravascular coagulation (DIC), 349 Drug metabolism, 410 Drug properties, 371–372 DTI-associated bleeding, 119 Dual antiplatelet therapy (DAPT), 414 ADP receptor inhibitor, 188 high bleeding risk surgery, 189 high-risk patients, 188–189 low bleeding risk surgery, 189 MACE, 189 moderate bleeding risk surgery, 189 platelet function loss, 188 Duplex ultrasonography, 396 Dysfibrinogenemia, 331, 352 E Ecarin clotting time (ECT), 120 Edoxaban, 90, 94–97, 137, 143–145, 186, 187, 304 oral factor Xa inhibitors, 224–225 prevention, stroke and systemic embolism, 94–96 treatment DVT, 95, 97 PE, 95, 97 EINSTEIN-DVT study, 91 EINSTEIN-PE study, 91 Elderly, 415 aging, 411 anticoagulants, 411 intracranial bleeding risk, 413, 414 triple therapy (see Triple antithrombotic therapy) warfarin, 410 Elective device implant, 242 Electrophysiology procedures atrial fibrillation, 240 cardioversion, 241 CHADS2 and CHA2DS2-VASc risk calculators, 240, 242 clinical judgment, practitioners, 240 evidence-based recommendations, anticoagulation, 240, 241 Index HAS-BLED, 240 laser lead extraction, 241 patient-specific risks and benefits, 241 pre-, peri- and post-procedural requirements, 241 WOEST trial, 241 Embryopathy, 399 Endogenous thrombin potential (ETP), 118, 121 ENGAGE AF-TIMI study, 94 Enoxaparin, 43, 44, 46–48, 50–53 Enzyme-linked immunosorbent assays (ELISAs), 368, 369 EQUINOX trial, 118 Erythrocytosis, 334 Essential thrombocythemia (ET), 333–335 European Ambulance Acute Coronary Syndrome (EUROMAX), 206 European Society of Cardiology (ESC), 65 European Society of Cardiology and European Association for Cardio-Thoracic Surgery (ESC/EACTS), 259 Excessive anticoagulation, 162 Extracorporeal membrane oxygenation (ECMO), 70, 115, 282 Extracranial hemorrhages, 413 F Factor VIII levels, 330 Factor V Leiden (FVL), 327, 338, 347, 350, 355 See also Inherited Thrombophilia Falls risks, 416 Fibrinolysis, 198 Fondaparinux, 74, 75, 77, 118, 122, 136–138, 142, 143, 145, 378, 428 ACS STEMI, 77 UA and NSTEMI, 77 adverse effects, 78, 378 anticoagulants, 78 antithrombin (AT), 72 breastfeeding, 79 data and clinical trials, 379 dosing, 78, 378 monitoring, 78, 378 NSTE-ACS, 204 once-daily dosing, 204 pediatric, 79 pharmacodynamics, 73 pharmacokinetics absorption, 72 age factor, 73 body weight, 73 distribution, 73 metabolism, 73 renal elimination, 73 pharmacology, 71, 72 pregnancy, 79 renal impairment, 378 STEMI, 204–205 synthetic pentasaccharide, 204 445 VTE prevention, 74, 75 treatment, 75 Food and Drug Administration (FDA), 88 Free and clot-bound thrombin, 88 Fresh frozen plasma (FFP), 24, 110, 112–115, 118 G Gastrointestinal and intracranial bleeding, 121 Gastrointestinal tract, 119 Glomerular filtration rate (GFR), 410 Gore Cardioform Septal Occluder, 283 H HAS-BLED score, 182, 183, 210, 411, 412 HELEX septal occluder, 283 Hemodialysis, 119 Heparin-induced thrombocytopenia (HIT), 40–42, 64, 201, 202, 363–370, 373–379, 382–384 aPTT, 66 argatroban, 63 bivalirudin, 64 CABG, 66 cardiac surgery, 379 complications amputation, 364 bilateral adrenal hemorrhage, 364 cutaneous manifestations, 363 skin lesions, 364 symptoms, 365 thrombosis, 363 cutaneous manifestations, 364 definition, 361 diagnosis, 365 dialysis, 379 DOACs, 382 incidence, 362 laboratory assays ELISAs, 368, 369 functional assays, 368 immunoassays, 368 lateral flow assays, 369 PaGIA, 369 management, 385 nomenclature, 361 OAC, 69 pathophysiology, 361–363 PCI, 379 (see also Percutaneous coronary intervention (PCI)) pharmacologic agents argatroban, 374 bivalirudin, 376–378 desirudin, 375, 376 fondaparinux, 378, 379 lepirudin, 374, 375 platelet count monitoring, 369, 370 pregnancy, 380 risk assessment, 383, 384 Index 446 Heparin-induced thrombocytopenia (HIT) (cont.) scoring systems 4T score, 365, 366 CPB, 368 HEP, 365–367 4T score, 366 therapy cardiac surgery, 383, 384 duration, 382 IVC filters, 383 LMWHs cross-reactivity, 382 platelet transfusion, 383 premature initiation, warfarin, 382 thrombosis, 362, 363 treatment algorithm, 373 anticoagulants, 370 dosing, 370 LMWHs, 370 VKA, 373 warfarin, 370 4T score, 63 venous limb gangrene, 364 VTE, 76 warfarin, 380, 381 Heparins, 2, 3, 115 antithrombin molecule, 115 coagulation serine proteases, 115 DVT, 361 embryopathy, 399 (see also Heparin-induced thrombocytopenia (HIT)) inhibit thrombin (factor IIa), 116 LMWHs (see Low-molecular-weight heparins (LMWHs)) polysaccharides, 115 prevention and treatment, 115 protamine sulfate, 111–112, 116–117 resistance, 40 thromboembolism risk, 402 transition therapy, 134–136 UFH (see Unfractionated heparin (UFH)) High bleeding risk procedure, 188, 189 High thrombotic risk atrial fibrillation, 179 mechanical prosthetic heart valves, 180–181 VTE, 176–177 Hip and knee replacement surgery, 92, 93 Hip replacement surgery, 89, 90 Hirudins (recombinant), 136 HIT Expert Probability (HEP), 365, 367 Homocysteine, 331, 332, 340 Homocystinuria, 332 I Idarucizumab, 119, 120, 231 Idrabiotaparinux, 118, 119 Idraparinux, 118 Implantable cardioverter-defibrillator, 242 Inferior vena cava (IVC) filters, 401 indications, 302–303 VTE management, 301–304 Inherited thrombophilia AT, 329, 330, 338 dysfibrinogenemia, 331 factor VIII, 330 FVL, 327, 338 homocysteine, 331, 332 lupus anticoagulant, 338 MTHFR, 331, 332 PGM, 327, 338 protein C deficiency, 328, 338 protein S deficiency, 328, 329, 338 INR recall interval, 167 International normalized ratio (INR), 18, 107, 182, 183 anticoagulant effect, 12 asymptomatic patients, 22 DOACs, 14, 19 dosing nomogram, 19 heparin therapy, 21 monitoring, 18 non-adherence with, 167 “no tamper zone”, 167 pediatric patients, 25 POC device, 156 PST and PSM, 156 recall interval, 167 stable patients and in-range, 159 standard targets, 167–168 telephonic AMS, 158 timing and goal pre-procedure values, 164 variability, 166 warfarin, 161 International Society on Thrombosis and Haemostasis (ISTH), 352 Intracranial bleeding risk, 413, 414 Intracranial hemorrhage (ICH), 21, 114, 141, 413, 431, 432 Intramuscular (IM) injection, 108 Intravenous (IV) infusion, 134 Ion-exchange chromatography, 111 Isolated distal DVT, 298 IV UFH anticoagulants DOACs, 142–143 LMWHs/fondaparinux, 142 K Knee and hip arthroplasty, 94, 96 L Laboratory testing, 346 Lariat device, 284 Left atrial appendage (LAA) occlusion devices, 246–247, 418, 419 description, 283 Lariat device, 284 The Watchman device, 283, 284 Left bundle branch block (LBBB), 197 Index Left ventricular assist device (LVAD) antithrombotic therapy management, 277–278 average life span, HF patients, 275 bleeding, 279–280 circulation effect, 275–277 (see also Long-term post-operative management) perioperative and preoperative management, 278 thrombosis, 280–281 Lepirudin adverse effect, 375 data and clinical trials, 375 dosing, 374, 375 monitoring, 375 Line-associated thrombosis, 433 LMWHs/fondaparinux to DOACs, 143 Longitudinal Investigation of Thromboembolism Etiology (LITE), 352 Long-term post-operative management anticoagulation therapy, 278–279 antiplatelet therapy, 279 Low bleeding risk procedure, 187–189 Low-molecular-weight heparin (LMWH), 46–48, 105, 115–118, 120, 122, 134, 136–138, 142, 145, 161, 162, 183, 304, 306, 310, 311, 318, 320, 336–337, 399, 428 anti-factor Xa monitoring, 46 AT and thrombin, 43 bleeding, 50 dose reductions, 50 dosing, 44, 45 enoxaparin, 44, 203 indications, 44 NSTE-ACS, 203 obesity anti-Xa levels, 46 dalteparin, 46, 48 dosing, 46 enoxaparin, 46 TBW-based dosing, 46 tinzaparin, 46 treatment, 47 pharmacodynamics, 43 pregnancy, 48, 50–52 product profiles, 43 protamine dosing, 51, 52 recurrent ischemia rates, 202 renal dysfunction, 48, 49 STEMI, 203–204 subcutaneous tissue, 203 thromboprophylaxis, 47 vs UFH, 44 Low thrombotic risk atrial fibrillation, 180 mechanical prosthetic heart valves, 181 VTE, 178 Lupus anticoagulant, 338 M Major adverse cardiovascular events (MACE), 188 Malignancy, 98 447 May-Thurner syndrome, 337, 338 Mechanical heart valves, 98 thrombosis risk, 259 warfarin anticoagulation, 259 Mechanical prosthetic heart valves description, 180 high thrombotic risk, 180–181 increased thrombogenicity, 180 low thrombotic risk, 181 moderate thrombotic risk, 180–181 thrombotic risk stratification, patients, 180, 181 Medication management baseline assessment and anticoagulant guidelines, 161, 163 bleeding and thromboembolic symptoms, 162–164 excessive anticoagulation, 162 invasive procedure, 164 patient education, 165 patient non-adherence, 162–164 UFH and LMWH, 161, 162 warfarin and INR monitoring, 161 Methylenetetrahydrofolate reductase (MTHFR), 331, 332, 354 MitraClip (valve repair), 271 Mitral annuloplasty rings, 270 Moderate bleeding risk procedure, 189 Moderate thrombotic risk atrial fibrillation, 179–180 mechanical prosthetic heart valves, 180–181 VTE, 178 Myeloproliferative neoplasms erythrocytosis, 334 ET and PV, 334, 335 Myocardial infarction (MI), 2, 66 N National Certification Board for Anticoagulation Providers (NCBAP), 160 National Comprehensive Cancer Network guidelines, 429 Natural anticoagulant thrombophilias ACP-r assay, 351 “activated protein C resistance”, 350 antithrombin, 348 AT, PC and PS deficiency, 348 CRP testing, 352 dysfibrinogenemia, 352 FIX and FXI, 352 FVIII and vWF, 351 FVL, 351 heparin presence, 348 homozygous PC deficiency, 348 laboratory findings, 348, 349 LITE, 352 PC deficiency, 350 peripheral blood white blood cell DNA, 351 prothrombin G20210A gene defect, 351 PS deficiency, 350 PTG and FVIII excess, 350 second-generation assays, 351 448 Natural anticoagulant thrombophilias (cont.) spectrophotometric methods, 349 type I, II and III PS deficiency, 350 Nonbacterial thrombotic endocarditis (NBTE), 434 Non-ST elevation myocardial infarction (NSTEMI), 65 Nonsteroidal anti-inflammatory medications (NSAIDs), 401 Non-ST-segment elevation acute coronary syndromes (NSTE-ACS), 197, 198, 200, 202, 203 bivalirudin, 205–206 fondaparinux, 204 LMWHs, 203 Non-valvular atrial fibrillation direct thrombin inhibitors, 88, 89 edoxaban, 94–96 rivaroxaban, 90, 91 Non-vitamin K oral anticoagulants, see Direct oral anticoagulants (DOACs) Novel anticoagulants (NOACs), see Direct oral anticoagulants (DOACs) O Obesity, 48, 99, 100 anti-Xa monitoring, 46, 48 dalteparin, 46, 48 dosing, 46 enoxaparin, 46 TBW-based dosing, 46 thromboprophylaxis, 47 tinzaparin, 46 treatment, 47 UFH, 35–37 Occlusion devices, 255 Oral anticoagulants (OAC) therapy, 69, 207, 414, 415 bleeding risks, 209–210 defined, 207 medications, 305–306 patient motivation factors, 310 recurrent cardiovascular events, 207 VKAs (see Vitamin K antagonists (VKAs)) VTE apixaban, 304 clinical trials, 304, 307–308 DOACs, 304 edoxaban, 304 medications, 304–306 VKOR, 304 warfarin, 304 Oral contraceptive pills (OCPs), 336 Oral direct thrombin inhibitors dabigatran etexilate, 222–223 ximelagatran, 222 Oral drug selection, 309–310 Oral DTIs, 119–120 Oral factor Xa inhibitors apixaban, 223, 224 edoxaban, 224–225 rivaroxaban, 223 Osteopenia, 40 Index P Pacemaker, 242, 248 Paget-Schroetter syndrome, 337 Panel-based AMS, 159 Paravalvular leak (PVL), 271–272 Parenteral anticoagulants, oral VKAs, 142 DTIs, 119 vs oral therapy, 304 Paroxysmal nocturnal hemoglobinuria (PNH), 335 Patient education, 165 Patient self-management (PSM), 156, 158 Patient self-testing (PST), 156, 158 Pentasaccharides, transition therapy, 60, 62, 71, 118, 134, 136 Percutaneous coronary intervention (PCI), 44, 65, 198, 374, 376, 379 acute MI, 66 argatroban, 64 bivalirudin, 64, 65 HIT argatroban, 65 bivalirudin, 65 Perioperative anticoagulation management bleeding patient/drug reversal, 97–98 bridging therapy, 96 low-bleeding-risk procedures, 97 monitoring, 98 Perioperative management, 185–187 See also Antiplatelet agents; Direct oral anticoagulants (DOACs); Warfarin Peripherally inserted central catheters (PICCs), 317, 433 Periprocedural bleeding risk antiplatelet therapies, 182 hysterectomy and hip/knee replacement, 182 oral anticoagulant therapies, 182 patient-related, 182–183 postoperative period, 181 procedural categories, 181 professional societies, 181 Periprocedural thromboembolic risk, see Venous thromboembolism (VTE) p-Glycoprotein efflux transporter, 88 PGM, see Prothrombin gene G20210A mutation (PGM) p-GP inhibitors, 88 p-GP system, 90 Pharmacodynamics (PD), 134 Pharmacokinetics (PK), 133 Pharmacology, 88, 90, 91, 143 direct factor Xa inhibitors, 90, 91 direct thrombin inhibitors, 88 Pharmacotherapy, 33 Phytonadione, 107 Plasma, warfarin, 110 Plasminogen activator inhibitor-2 (PAI-2), 394 Platelet count monitoring, 369, 370 Platelet factor (PF4), 361 Pneumatic compression devices, 398 Point-of-care (POC) testing, 156 Polycythemia vera (PV), 333, 334 Index Polyethoxylated castor oil (PEO-CO), 109 Practice-based and registry studies, 230–231 Pregnancy argatroban, 71 bivalirudin, 71 direct thrombin inhibitors, 400 DOACs, 400 DVT and PE diagnosis APC, 396 clinical findings, 395 CT/VQ, 397 D-dimer test, 396 duplex ultrasonography, 396 management, 398 Wells rule, 395 FDA classification, 401 fondaparinux, 79, 400 HIT, 380, 400 IVC filters, 401 LMWH, 48, 50–52 mechanical valves, 402, 403 PEs, 392 pneumatic compression, 398 prosthetic heart valves, 274–275 SVT, 401 thrombocytopenia, 400 thromboembolism prophylaxis, 394 treatment of VTE LMWH, 399 UFH, 399 vitamin K antagonists, 399 UFH, 36, 38 VTE, 336 duration of therapy, 401 risk assessment score, 395, 396 risk factors, 392–394 warfarin, 24, 25 Primary prophylaxis after hip replacement surgery, 89, 90 Prophylaxis, high-risk medical patients, 99 Prosthetic heart valves aortic regurgitation treatment, 256 biologic tissue valves, 256 classification, 256 contemporary mechanical valves, 256 designs, 256, 257 Hufnagel’s caged-ball valve, 256 pregnancy, 274–275 thromboembolic complications, 258 tilting disk mechanical valve design, 256 Prosthetic valve thrombogenicity hemodynamics and construction materials, 258 patient risk factors, 258 valve construction materials, 258 Prosthetic valve thrombosis, embolic complications, 273–275 Protamine sulfate, heparins, 39, 111–112, 116 Protein C deficiency, 328, 338 prothrombin time (PT), 328 type I and II deficiency, 328 VTE risk, 328 449 Protein S deficiency, 328, 329, 338 Prothrombin complex concentrates (PCCs), 23, 24, 119, 120 doses, 111 3-factor, 112, 113 4-factor, 113 FFP vs FFP transfusions, 110, 112 ion-exchange chromatography, 111 RCTs, 112 retrospective cohort study, 113 reversal of VKAs, 113 safety, 113 types, 111, 112 viral inactivation/elimination techniques, 111 VKA-associated coagulopathy, 113 VKA therapy, 110 Prothrombin gene G20210A mutation (PGM), 327, 338 Prothrombin gene mutation (PTG), 347, 356 Prothrombin time (PT), 107, 157 Puerperium, 398 Pulmonary embolism (PE) acute, 299–301 (see also Pregnancy) treatment and secondary prevention apixaban, 94, 95 direct thrombin inhibitors, 88–90 edoxaban, 95, 97 rivaroxaban, 91, 92 Pulmonary veins (PV), 242–244, 419 Purple toe syndrome, 21 Q Quality of life, 418 R Randomized clinical trials (RCTs), 105, 108 Recombinant factor VIIa (rFVIIa) administration, 114 AERS database, 115 arterial and venous thromboembolism, 114 bleeding, 114 dose, 114 ECMO lines, 115 FDA, 115 hemostatic effect, 114 intracranial hemorrhage, 114 off-label use, 115 plasma half-life, 114 prohemostatic agent, 114 RCTs, 115 rescue therapy, 115 safety, 114 thrombin burst, 114 thromboembolic events, 115 VKA-associated coagulopathy/bleeding, 115 VKA-associated intracranial hemorrhage, 114 VKA-associated major bleeding, 114 VTE events, 115 450 Recommendations for transition therapy DOACs, 143, 145 warfarin, 143–145 IV UFH, 142 parenteral anticoagulants, oral VKAs, 142 RE-LY trial, 88 RE-MEDY trial, 88, 89 Renal dysfunction, 48, 49 RE-SONATE trial, 88, 89 Retinal vein thrombosis, 318 Retrospective cohort study, 113 Reversal strategies andexanet alfa, 117 antithrombotic therapy, 105 ciraparantag, 117, 118 classes of drugs, 105 clinical trials, 106 direct oral factor Xa inhibitors, 120–122 DOACs, 106 heparin (see Heparins) oral DTIs, 119–120 parenteral DTIs, 119 pentasaccharides, 118–119 venous and arterial thromboembolism, 105 randomized clinical trials (RCTs), 105 VKAs, 106–107 VTE (see Venous thromboembolic events (VTE)) warfarin (see Warfarin) RE-VERSE AD study, 120 RIETE score, 312 Risk assessment tools, 411 Risk stratification tools, 417 Rivaroxaban, 137, 143–145, 186 DOACs, 210–212 oral factor Xa inhibitors, 223 prevention stroke and systemic embolism, non-valvular atrial fibrillation, 90, 91 VTE, hip and knee replacement surgery, 92, 93 treatment and secondary prevention DVT, 91–92 PE, 91, 92 Rivaroxaban-treated participants, 121 S Septal closure devices, 282 Sequential compression devices (SCDs), 345 Serotonin release assay (SRA), 41 Shared decision-making process, 299 Short-term parenteral therapy, 183–185 Skin necrosis, 20, 21 Splanchnic vein thrombosis, 317 ST-elevation myocardial infarction (STEMI), 65 Stroke and systemic embolism, 1, 2, 88–91, 93–96 atrial fibrillation, apixaban, 93, 94 non-valvular atrial fibrillation direct thrombin inhibitors, 88, 89 edoxaban, 94–96 rivaroxaban, 90, 91 Index ST-segment elevation myocardial infarction (STEMI), 44, 197 bivalirudin, 206–207 fondaparinux, 204–205 LMWHs, 203–204 revascularization with PCI, 200 total/near-total occlusion, 198 Subcutaneous (SC) injections, 134 Superficial vein thrombosis (SVT), 76, 318, 401 Systemic thrombolytics, dosing options, 300 T Tamoxifen, 336 TandemHeart, extracorporeal centrifugal pump, 282 Target-specific oral anticoagulants (TSOACs), see Direct oral anticoagulants (DOACs) Team-based AMS, 159–160 Telephone vs in-office AMS model, 158, 159 Temporary mechanical circulatory support, 281, 282 Therapeutic range (TTR), 141 Thrombin generation time (TGT), 118 Thrombocytopenia, 361, 365, 400, 431 See also Heparin-induced thrombocytopenia (HIT) Thromboembolism anticoagulation risks, 219–221 non-valvular AF, 218 prophylaxis, 394 warfarin, 218 Thrombolysis acute DVT, 301 acute PE, 299–301 catheter-directed, 319 contraindications, 301 dosing options, 300 Thrombophilia, 99, 317, 318, 393 acute thrombosis, 338 anticoagulants, 338 anticoagulation, 337, 339 APS, 338 ASH recommendations, 346 clinical conditions, 347 clinical events/intervention, 338 hospitalization and comorbid illness, 346 laboratory tests, 347–349 patient-related, therapy-related and laboratory-related factors, 346 venous and arterial thromboembolism, 346 Thromboprophylaxis, 33, 46–48, 51 Thrombosis, 297, 362, 363, 368, 374, 379, 382, 383, 387 cancer patients, cerebral vein, 317 DVT (see Deep vein thrombosis (DVT)) retinal vein, 318 splanchnic vein, 317 SVT, 318 venous, 317–319 Tinzaparin, 43–46, 50 Tissue factor-independent pathways, 114 Transcatheter aortic valve replacement, 272–273 Index Transfusion-related acute lung injury (TRALI), 110 Transition therapy aPTTs, 134 bridging therapy, 138–140 concept of, 137 different anticoagulants, 138 DOACs, 134, 137, 138, 141 drug development, 133 DTIs, 134, 136 heparin, 134–136 ICH, 141 ideal anticoagulant, 134 parenteral anticoagulant, 138 pentasaccharides, 136 recommendations, 142–145 RE-LY trial, 141 safety outcomes, 141 TTR, 141 UFH, 133, 138 VKAs, 133, 136–138 Triple antithrombotic therapy BMS, 415 hemorrhagic risk, 416 OAC, 415 risk of falls, 416 WOEST trial, 415 Triple oral anticoagulant therapy (TOAT), 208–209 Trousseau’s syndrome, 425 “4T score”, 202 U Unfractionated heparin (UFH), 40, 42, 115–117, 120, 122, 133, 134, 136–138, 142, 145, 161, 162, 183, 399 ACS, 201 activated AT, 200 adjustments, 200 antithrombin (AT), 32 aPTT, 33 bleeding risk, 39 complications, 201–202 heparin resistance, 40 HIT, 40, 42 osteopenia, 40 dosing, 33, 34 indications, 33 vs LMWH, 33 monitoring, 34, 35 obesity, 35–37 pharmacodynamics, 33 pharmacokinetics, 33 pregnancy, 36, 38 protamine sulfate, 39 reperfusion with fibrinolytic therapy, 201 STEMI/NSTE-ACS patients, 200 thromboembolism prevention, 38 Unstable angina (UA), 197, 201, 204 US Food and Drug Administration (FDA), 89, 115 451 V Valve repair, 269–272 Valvular atrial fibrillation, 98 Valvular heart disease, 254 clinical decision-making, 258 epidemiology, 257–258 Vascular endothelial growth factor (VEGF), 337 Venous limb gangrene, 364, 370 Venous thoracic outlet syndrome, 337, 338 Venous thromboembolism (VTE), 1, 3, 13, 24, 33, 74, 75, 92–94, 96, 115, 298, 299, 301–311, 346, 347, 352, 354, 393, 396, 411 anticoagulation options, 299 apixaban, knee and hip arthroplasty, 94, 96 bevacizumab, 337 cancer surgery, 426 catheter-associated, 317 CDC prevention, 298 cerebral vein thrombosis, 317 chemo- and immunotherapeutic agents, 427–428 clinical trials, 307–308, 313–315 CLOT trials, 426 disruptions, 297 DOACs, 428, 429 DVT (see Deep vein thrombosis (DVT)) education topics, 309 high thrombotic risk, 176–177 HIT, 76 low thrombotic risk, 178 management, 299–300 acute, 299 IVC filter, 301–304 thrombolysis (see Thrombolysis) moderate thrombotic risk, 178 OCP, 336 outpatient therapy (see VTE outpatient therapy) patient categories, 340 PE, 176 pregnancy, 336 risk assessment score, 396 thrombophilias, 393 prevention, 429, 431 abdominal surgery, 74, 75 in hip and knee replacement surgery, 92, 93 medically ill patients, 75 orthopedic surgery, 74 prevention in medical inpatients, 318–319 principal mechanisms, 325 retinal vein thrombosis, 318 risk factor, 298 risk scores, 311 splanchnic vein thrombosis, 317 SVT, 76, 318 tamoxifen, 336 thrombotic risk stratification, patients, 176, 177 treatment, 75, 312 Vitamin K, 10, 15, 17, 22, 23, 25, 27 anaphylactoid reactions, 109 anaphylaxis, 109 clinical trials, 108 Index 452 Vitamin K (cont.) guidelines, 108 IM injection, 108 INRs, 108, 109 intravenous/subcutaneous route, 108 K3, 107 low-dose oral tablets, 108 PEO-CO, 109 RCT trial, 108, 109 SC, 108 treatment, 109 vitamin K1/phytonadione, 107 vitamin K2, 107 warfarin-associated coagulopathy, 108 warfarin reversal prior to invasive procedures, 108 Vitamin K antagonists (VKAs), 2, 93, 134, 136–138, 141, 163, 370, 380, 399, 412, 428 after ACS, 208 bleeding events, 109 clotting factors, 207 diet and genetics, 207 effect of warfarin, 107 INR, 108 medications, OAC therapy, 207 optimal IV dose, 109 reversal strategies, 106 therapeutic targets, INR, 207 transition therapy, 136, 137 Vitamin K epoxide reductase (VKOR), 10, 304 Vitamin K1 therapy, 107 VKA-associated coagulopathy, 113 VTE outpatient therapy discontinuation, 316 extended prophylaxis aspirin, 316–317 DOACs, 312–316 duration, 311–315 warfarin, 311 first months cancer, 310, 311 DOACs, 306 oral anticoagulants, 304 oral drug selection, 309–310 parenteral vs oral therapy, 304 patient-specific clinical factors and individual preferences, 304 warfarin, 304–306, 309 extended treatment phase, 316 oral anticoagulants, 304–308 See also Pregnancy W Warfarin, 2, 5, 15, 16, 18–22, 88–98, 100, 136–138, 141–143, 311, 410 absorption, 10 administration, 16 adverse effects bleeding, 21, 22 purple toe syndrome, 21 skin necrosis, 20, 21 anticoagulant effect, 12 anticoagulation, 259 antithrombotic effect, 12, 107 argatroban, 381 asymptomatic patients INR > 9, 22 INR ≤ 9, 22 bleeding, 17, 22–24 breastfeeding, 25 calciphylaxis, 21 cancer, 433 clinical conditions and effects, 16 distribution, 11 DOACs, 12–14, 143–144 dosing algorithms, 166 maintenance guidelines, 15, 16 nomogram, 15, 18, 19 response factor, 15 drug interactions, 11 emergent procedures, 24 herbal and nutritional products, 12 HIT, 370, 380, 381 INR monitoring, 107, 110, 161, 259–261, 266 invasive procedures, 20 LMWH, 20 management, labor-intensive endeavor, 154 metabolism, 12 monitoring, 17, 18 patient education, 13–15 PCC, 110–114 pediatric patients, 25 perioperative management high bleeding risk, 183 short-term parenteral/bridge therapy, 183–185 surgical procedure risks, 183 vitamin K-dependent factors, 183 VTE and ATE prevention and treatment, 183 pharmacodynamics, 12, 13 pharmacokinetics, 11–13 pharmacology, 10 plasma, 110–112 pregnancy, 24–25 PT, 107, 109 regeneration, 109 renal impairment, 12 rFVIIa, 114–115 stereoisomers, 10 supratherapeutic INR, 110 therapy, 12 thromboembolic risk, 20 vitamin K, 107–109 VKAs, 109 VTE, 304–306, 309, 311 Warfarin-associated coagulopathy, 108 The Watchman device, 247, 283, 284 Waterfall\cascade model, 325 X Ximelagatran drug, 222 .. .Anticoagulation Therapy Joe F Lau • Geoffrey D Barnes Michael B Streiff Editors Anticoagulation Therapy Editors Joe F Lau, MD, PhD Associate Professor... Antagonist Therapy Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement Bridging Anticoagulation in Patients who Require Temporary Interruption of Warfarin Therapy. .. of Dual Therapy with Dabigatran vs Triple Therapy Strategy with Warfarin in Patients with NVAF that have undergone PCI with Stenting Randomized Evaluation of Long-Term Anticoagulation Therapy