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Senior Acquisitions Editor: Sharon Zinner Editorial Coordinator: Lauren Pecarich Production Project Manager: Linda Van Pelt Design Coordinator: Holly McLaughlin Manufacturing Coordinator: Beth Welsh Marketing Manager: Rachel Mante Leung Prepress Vendor: S4Carlisle Publishing Services Copyright © 2018 Wolters Kluwer All rights reserved This book is protected by copyright No part of this book may be reproduced or transmitted in any form or by any means, including as photocopies or scanned-in or other electronic copies, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotations embodied in critical articles and reviews Materials appearing in this book prepared by individuals as part of their official duties as U.S government employees are not covered by the above-mentioned copyright To request permission, please contact Wolters Kluwer at Two Commerce Square, 2001 Market Street, Philadelphia, PA 19103, via e-mail at permissions@lww.com, or via our website at lww.com (products and services) 9 8 7 6 5 4 3 2 1 Printed in China Library of Congress Cataloging-in-Publication Data Names: Herzog, Eyal, editor Title: Herzog’s CCU book / [edited by] Eyal Herzog Other titles: CCU book | Cardiac care unit book Description: Philadelphia: Wolters Kluwer Health, [2018] | Includes bibliographical references and index Identifiers: LCCN 2017044559 | eISBN 9781496362681 Subjects: | MESH: Heart Diseases | Critical Care Classification: LCC RC682 | NLM WG 210 | DDC 616.1/2—dc23 LC record available at https://lccn.loc.gov/2017044559 This work is provided “as is,” and the publisher disclaims any and all warranties, express or implied, including any warranties as to accuracy, comprehensiveness, or currency of the content of this work This work is no substitute for individual patient assessment based upon health care professionals’ examination of each patient and consideration of, among other things, age, weight, gender, current or prior medical conditions, medication history, laboratory data, and other factors unique to the patient The publisher does not provide medical advice or guidance, and this work is merely a reference tool Health care professionals, and not the publisher, are solely responsible for the use of this work, including all medical judgments, and for any resulting diagnosis and treatments Given continuous, rapid advances in medical science and health information, independent professional verification of medical diagnoses, indications, appropriate pharmaceutical selections and dosages, and treatment options should be made and health care professionals should consult a variety of sources When prescribing medication, health care professionals are advised to consult the product information sheet (the manufacturer’s package insert) accompanying each drug to verify, among other things, conditions of use, warnings, and side effects and identify any changes in dosage schedule or contraindications, particularly if the medication to be administered is new, infrequently used, or has a narrow therapeutic range To the maximum extent permitted under applicable law, no responsibility is assumed by the publisher for any injury and/or damage to persons or property, as a matter of products liability, negligence law or otherwise, or from any reference to or use by any person of this work LWW.com To my family, patients, colleagues, and trainees who have taught me so much over the years Eyal Herzog Contributors Eric Adler, MD Medical Director Cardiac Transplant Clinical Professor of Medicine University of California San Diego La Jolla, California Jeanine Albu, MD, FACP Chief Division of Endocrinology, Diabetes and Nutrition Mount Sinai St Luke’s and Mount Sinai West Hospitals Professor of Medicine Icahn School of Medicine at Mount Sinai New York, New York Diana Anca, MD Cardiothoracic Anesthesiologist Assistant Clinical Professor of Anesthesiology Icahn School of Medicine at Mount Sinai Mount Sinai St Luke’s Hospital New York, New York Edgar Argulian, MD, MPH, FACC, FASE Assistant Professor of Medicine Co-Director Echocardiography Laboratory Mount Sinai St Luke’s Hospital Mount Sinai Heart Institute Icahn School of Medicine at Mount Sinai New York, New York Emad F Aziz, DO, MBCHB, FACC, FHRS Director Cardiovascular Research Associate Director of Cardiovascular Fellowship Associate Professor of Medicine Icahn School of Medicine at Mount Sinai New York, New York Joshua Aziz, BMEs Rutgers University New Brunswick, New Jersey May Bakir, MD Department of Cardiology Mount Sinai St Luke’s Hospital New York, New York Sandhya K Balaram, MD, PhD Associate Professor of Surgery Department of Cardiovascular Surgery Icahn School of Medicine at Mount Sinai Mount Sinai St Luke’s Hospital New York, New York Gabriela Bambrick-Santoyo, MD Director of Simulation Associate Program Director Internal Medicine Residency Program Hackensack University Medical Center Mountainside Hospital 15 min PCC preferred option in patients with TBI and/or ICH a Evidence does not support complete reversal of the anticoagulant effect Use clinical judgment and consider other treatment options FFP, fresh frozen plasma; ICH, intracranial hemorrhage; INR, international normalized ratio; IV, intravenously; PCC, prothrombin complex concentrate; PO, per oral; TBI, traumatic brain injury TABLE 31.6 Protamine Sulfate Dosing for Low-Molecular-Weight and Unfractionated Heparins TIME SINCE LAST LMWH DOSE PROTAMINE DOSE FOR EACH: DALTEPARIN 100 UNITS OR ENOXAPARIN 1 MG 12 h Not likely useful (consider 25 mg fixed dose) TIME SINCE LAST HEPARIN DOSE PROTAMINE DOSE FOR EACH 100 UNITS OF HEPARIN Immediate 1 mg (or 25 mg fixed dose) 30 min 0.5 mg (or 10 mg fixed dose) >2 h 0.25 mg (or 10 mg fixed dose) Consider a second protamine dose (50% of first dose) if prolonged aPTT continues aPTT, activated partial thromboplastin time; LMWH, low-molecular-weight heparin The source of bleeding has to be appropriately identified, managed, and treated such that rapid reversal of anticoagulation will not necessarily solve the underlying bleeding.4 Thus, once bleeding is identified, the first priority is to locate the source and discontinue the anticoagulant agent The clinical stability of the patient should serve as a guide for the next steps For example, significant blood loss causing hypovolemic shock from a gastrointestinal bleed may require volume administered with blood transfusions In addition, directly reversing the anticoagulant effect may also aid in restoring the bleeding diathesis On the other hand, an intracranial hemorrhage generally requires less volume, but directly reversing the anticoagulant effect may be preferred Volume restoration during hemorrhage, for example, with crystalloids, colloids, and/or blood transfusion protocols is beyond the scope of this chapter, but an overview of anticoagulant reversal agents is provided Reversal agents and strategies discussed include idarucizumab for dabigatran, andexanet alfa (andexanet) for anti-FXa NOACs and LMWHs, prothrombin complex concentrates (PCCs) with vitamin K for warfarin, and protamine sulfate for UFH Andexanet is currently in later phases of premarketing clinical trials An additional agent, ciraparantag, is in very early stages of development with a broader spectrum of anticoagulants potentially reversed by this agent IDARUCIZUMAB FOR DABIGATRAN REVERSAL Idarucizumab is a monoclonal antibody fragment that binds dabigatran with a 350-fold or so higher affinity to that of thrombin.18 As a result, idarucizumab adheres to thrombin-bound dabigatran and neutralizes its activity Currently, idarucizumab is approved by the US FDA for the reversal of the anticoagulant effects of dabigatran, needed for emergency surgery/urgent procedures or in lifethreatening or uncontrollable bleeding The RE-VERSE AD trial examined the safety and reversal capacity of idarucizumab on dabigatran in patients who had a serious bleeding event or required reversal for an urgent procedure.18 Serious bleeding was defined as overt, uncontrollable, or life-threatening bleeding that was judged by the treating clinician to require a reversal agent, and an urgent procedure was defined as requiring surgery or other invasive procedures that could not be delayed for at least hours and for which normal hemostasis was required.18 Idarucizumab was administered as a 5-g dose divided into two separate bolus infusions of 2.5 g in 50 mL within 15 minutes of one another The results demonstrated rapid and complete reversal effects of dabigatran in 88% to 98% of patients.18 Idarucizumab is not without potential side effects that may include direct effects of the agent such as anaphylaxis, other hypersensitivity reactions, and serious reactions with hereditary fructose intolerance because sorbitol is a component of the preparation A prothrombotic effect of dabigatran reversal by idarucizumab leading to thrombosis may also occur once the anticoagulant effects have been reversed, for example, in those with a high CHA2DS2-VASc score In some patients, a delayed increase in dabigatran serum concentrations, such as 12 to 24 hours after idarucizumab administration, may reflect an increase in clotting time markers possibly due to intravascular redistribution of dabatran.18 It is unknown whether additional doses of idarucizumab would be effective and safe in such scenarios.18 Because the cost of each dose of idarucizumab is currently in the several thousands of US dollars, it may be fiscally prudent for hospitals and health systems to create multidisciplinary policies, procedures, and standardized protocols Components of such consensus documents may include selecting appropriate clinical scenarios for use, monitoring parameters and frequencies, procurement quantities, and location of refrigerator storage within the institution to avoid waste ANDEXANET ALFA FOR FACTOR XA INHIBITOR REVERSAL Not yet approved by the US FDA, andexanet alfa (andexanet) is a recombinant modified human FXa decoy protein that reverses the inhibitory effects of antiFXa agents.19 These counteractive effects of FXa inhibition by NOACs and LMWHs restore FXa activity and therefore the potential for clot formation The ANNEXA-4 trial is actively evaluating the activity of andexanet in patients with acute major bleeding within 18 hours of the administration of an FXa inhibitor, including apixaban, edoxaban, rivaroxaban, and enoxaparin.19 Andexanet was administered by an initial bolus infusion over 15 to 30 minutes followed by a 2-hour infusion to maintain activity against the anti-FXa agent Doses were relatively lower for patients who had taken apixaban or rivaroxaban more than 7 hours before the administration of andexanet and higher for patients who had taken enoxaparin, edoxaban, or rivaroxaban 7 hours or less before the administration of the bolus dose or at an unknown time Clinical monitoring parameters for efficacy endpoints included changes in anti-FXa activity and hemostasis within a 12-hour period.19 The most updated preliminary analysis of this ongoing trial demonstrated 79% of patients with relatively effective hemostasis after receiving the bolus and 2-hour infusion of andexanet There were no reported serious side effects attributed directly to andexanet; however, thrombotic events occurred in 18% of patients.19 Additional data from the ongoing ANNEXA-4 trials, as well as from controlled trials, are needed to determine the safety of thrombotic event frequency compared with what is expected.19 Further research is necessary to understand how this antidote will be used in clinical practice PROTHROMBIN COMPLEX CONCENTRATES WITH VITAMIN K FOR WARFARIN REVERSAL The traditional approach to treat bleeding associated with warfarin is to administer fresh frozen plasma (FFP) However, there are significant drawbacks with using FFP All clotting factors are included in FFP, derived from human plasma, which often contains numerous antibodies This increases the risk of infusion-related reactions, with the most severe consequence being transfusionrelated acute lung injury In addition, an extensive volume (15 mL/kg per unit) is required for reversal, which may be a limiting factor for volume-restricted patients with poor cardiovascular status FFP also possesses its own intrinsic INR ranging from 1.5 to 1.7, owing to the presence of all clotting factors PCC is a concentrated form of factors II, VII, IX, and X and proteins C and S, which specifically targets all mechanisms involved with warfarin and includes those involved with NOACs This product requires a higher degree of purity for processing compared with FFP, which dramatically lessens the likelihood of transfusion-related complications The major advantages of PCC is that reversal requires much smaller volumes (1 to mL/kg per unit), which can be infused over a shorter period of time Vitamin K may be administered as an individual agent in the setting of INR elevations with warfarin without significant bleeding When administered as a single agent as intravenous or po, it is extremely slow to reverse the effects of INR, which will not be evident until approximately 24 to 48 hours after administration Over time, concentrated vitamin-K–dependent clotting factors have been used until recently with the introduction of 4-factor (4F)-PCC with vitamin K In a multicenter, open-label, randomized, plasma-controlled noninferiority clinical trial using FFP versus 4F-PCC in patients with acute bleeding associated with VKA therapy for the achievement of effective hemostasis within 24 hours was evaluated Superiority was also examined through reduction of INR to ≤1.3 within 30 minutes of the completed infusion.20 Effective hemostasis was defined as cessation of bleeding within hours of the end of the infusion and no additional coagulation intervention required within 24 hours Within 24 hours, hemostasis was achieved in 72.4% of those receiving 4F-PCC versus 65.4% receiving FFP, demonstrating noninferiority.20 There was no statistically significant difference detected for mortality or length of stay between 4F-PCC and FFP Serious adverse events associated with reversal of VKAs with 4F-PCC were reported in 31% of patients, of which only 10 were deemed directly related to treatment.20 When compared with FFP, rates of serious adverse events appeared similar; however, no clinical trial has been powered to specifically evaluate differences in safety Tables 31.4 and 31.5 outline the specific information regarding the dosing for FFP, PCC, and vitamin K for anticoagulation reversal PROTAMINE FOR REVERSAL OF HEPARINS Particularly relevant to those patients requiring bridging with UFH when initiating therapy with warfarin, protamine will provide an effective means for stopping acute bleeding There is no role for the use of protamine for reversal of NOACs Protamine provides complete reversal of anticoagulant effects from UFH and partial reversal with LMWH, enoxaparin and dalteparin See Table 31.6 for dosing recommendations for protamine, which is based on administration times for each anticoagulant Protamine should be administered slowly, with a maximum dose of 50 mg over 10 minutes to minimize the adverse effect of hypotension If outcomes are promising from the future reversal agent in the pipeline, ciraparantag may end up replacing protamine for these agents, noting its broad effect upon reversal of anticoagulants REINITIATING ANTICOAGULATION POST BLEEDING When bleeding occurs, especially from the gastrointestinal or urinary tracts, the presence of an underlying occult lesion should always be considered.3 Once hemostasis is achieved, the decision whether and when to reinitiate anticoagulation therapy after reversing the anticoagulant effects for a severe bleeding episode may be necessary and should be considered on an individualized basis.4 The ongoing use of the CHADS2-DS2-VASc and HASBLED systems together may provide guidance in this particular decision-making process In patients for whom anticoagulation therapy is needed after hospitalization for a gastrointestinal bleed, reinitiating anticoagulation within 90 days of the event demonstrated positive outcomes on thrombotic events and death.21, 22 PERIOPERATIVE BRIDGING FOR SURGERY AND PROCEDURES When chronic anticoagulation therapy is required, such as in AF, adequate anticoagulation before and after surgery or an invasive procedure may be needed, particularly when the risk of thromboembolism is high The concept of anticoagulant “bridging” is essentially administering a short-acting anticoagulant (eg, UFH or LMWH) during the time when a long-acting warfarin is being withheld before the surgery, then continued after the surgery or procedure until the long-acting anticoagulant is again within the target therapeutic range.23 Because the NOACs have a faster offset of action compared with warfarin and a rapid onset of action, bridging with UFH or an LMWH may not be necessary, unless the patient is not able to take oral therapy such as with gastric resection or postoperative ileus.23 Not all procedures require anticoagulants to be held, for example, minor dental and skin procedures, cataract extraction, and selected cardiac device implantation.23 The NOACs need to generally be held for 1 to 4 days before the procedure, with the interruption interval depending on the specific agent, patient’s renal function, and type of bleeding risk of the procedure.24 Table 31.7 provides recommendations by the manufacturers and from clinical trials for the timing of discontinuing anticoagulants before surgery or procedures Postoperative resumption of NOACs should take into account their rapid onset of action (1 to hours postingestion), and can be restarted approximately 24 hours after low-bleed risk and 48 to 72 hours after high-bleed risk procedures.24 With urgent surgery, there is no evidence suggesting higher bleeding rates with NOACs as compared with patients treated with warfarin.24 The BRIDGE investigators conducted a randomized, double-blind, placebocontrolled trial to determine whether foregoing anticoagulant bridge therapy in patients with AF treated with warfarin is noninferior to bridging with the LMWH dalteparin and superior with respect to major bleeding.25 The mean CHADS2 score was 2.3 (CHA2DS2-VASc score was not used for risk stratification at the time of the trial) with only about one-third with a score of 3 or higher, suggesting a relatively lower risk of thrombosis It is important to point out that patients at high risk for thrombosis, such as those with CHA2DS2VASc scores or greater, and/or those requiring higher intensity warfarin, for example, with mechanical mitral valves may still require perioperative bridge therapy because these scenarios were excluded in the study.25 In addition, surgical procedures associated with high risks of thrombosis, such as carotid endarterectomy, major cancer surgery, cardiac surgery, or neurosurgery were excluded from the trial The results of this trial, demonstrated in patients with AF on warfarin therapy, that LMWH perioperative bridge therapy did not prevent thromboembolic events, but did increase the risk of major bleeding It therefore may be reasonable to forego bridging warfarin with UFH or an LMWH in patients at relatively low thromboembolic risk and undergoing procedures to avoid clinically significant bleeding Using this approach, the patient would therefore discontinue warfarin usually until the INR decreases to below 1.5 (approximately days) before the procedure without being additionally anticoagulated The perioperative treatment plan should therefore be designed in collaboration with the operating clinician and the patient ANTIPLATELET THERAPIES WITH ATRIAL FIBRILLATION The Stroke Prevention in Atrial Fibrillation-1 (SPAF-1) trial from the early 1990s is the only trial among eight or so evaluated in a meta-analysis to show the benefit of aspirin alone in preventing stroke among patients with AF.4 The dose seemingly effective was aspirin 325 mg once daily Aspirin was not effective in those older than 75 years of age, did not prevent severe stroke, and has not been studied in low-risk populations.4 Clopidogrel 75 mg once daily plus aspirin 75 to 100 mg once daily was evaluated for stroke prevention in the Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE-W) trial and terminated early because in patients with a mean CHADS2 score of 2, the combination of antiplatelet agents was inferior to warfarin (target INR 2 to 3).4 The ACTIVE-A trial compared clopidogrel plus aspirin versus aspirin alone and demonstrated superiority in stroke prevention of the combination antiplatelet therapy to aspirin alone; however, the benefits were diminished by the increases in severe bleeding rates The AVERROES study was a direct comparison between aspirin and the FXa inhibitor apixaban.4, 26 This double-blind study of 5,599 patients deemed unsuitable for warfarin therapy were randomized to apixaban 5 mg twice daily (2.5 mg twice daily for those who had two of the following three: age ≥ 80 years, weight ≤ 60 kg, serum creatinine ≥ 1.5 mg/dL) or to aspirin 81 or 325 mg once daily The trial was prematurely terminated owing to the observed superiority of apixaban over aspirin for the occurrence of any stroke or systemic embolism Major bleeding rates were similar between apixaban and aspirin With respect to triple antithrombotic therapy with concomitant dual antiplatelet agents and NOACs, there is a paucity of literature for evaluation Several landmark trials that studied NOACs for stroke prophylaxis with NVAF excluded the combination of aspirin with a P2Y12 inhibitor (eg, clopidogrel, prasugrel, ticagrelor).8–11,26 Therefore, an important remaining unanswered question is in patients with AF requiring anticoagulation and at the same time dual antiplatelet therapy with aspirin and a P2Y12 inhibitor for coronary intervention such as stenting The SAFE-A study that compares 1-month versus 6-month P2Y12 inhibitor therapy in combination with aspirin and apixaban, in patients with AF who undergo drug-eluding stent implantation, is currently under way.27 The primary outcome will be the incidence of all bleeding complications occurring within 12 months Ultimately, this study will provide data that may guide the optimal management of triple antithrombotic therapy Additional medications that have antiplatelet properties should be used with caution when taken concomitantly with NOACs Such agents include NSAIDs, such as naproxen, ibuprofen, celecoxib, diclofenac, and meloxicam In addition, selective serotonin reuptake inhibitors (SSRIs) commonly used as antidepressants, such as paroxetine, fluoxetine, sertraline, citalopram, and escitalopram, and serotonin norepinephrine reuptake inhibitors (SNRIs) commonly used as antidepressants and neurogenic pain analgesics, such as duloxetine and venlafaxine, should be used with caution ABILITY TO PAY AND LIKELY TO ADHERE TO THERAPY Perhaps the greatest risk factor for thrombotic events with AF is the inability to take the prescribed anticoagulant on a daily basis.4 This is particularly important with NOACs because the duration of action is shorter than that of warfarin, so missing even one dose of a NOAC increases the risk of thrombosis The reasons for nonadherence to a drug therapy regimen are multifaceted and highly individualized Barriers that cause patients not to take their medication as prescribed may include the health literacy of the patient and/or caregiver, emotional state and acceptance of the need for chronic daily medications, side effects and intolerances, and the inability to obtain the drug because of cost or other reasons Discontinuing a NOAC should not occur without proper anticoagulant coverage, such as with warfarin and/or LMWH for patients who will still require treatment.4 During the transitions of care when patients are admitted to and discharged from the hospital and/or patient care units, it is critical to accurately reconcile the medication regimen, including anticoagulant therapy to avoid thromboembolic events from omission errors Prescribers are encouraged to discuss outpatient prescription drug coverage and the patient’s intentions and ability to continue the oral anticoagulant therapy upon hospital discharge REFERENCES You JJ, Singer, DE, Howard PA, et al Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines Chest 2012;141:e531S-e575S Hart RG, Pearce LA, Aguilar MI Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation Ann Intern Med 2007;146:857-867 Ageno W, Gallus AS, Wittkowsky A, et al Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines Chest 2012;141:e44S-e88S January CT, Wann LS, Alpert JS, et al 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary JACC 2014;64(21):2246–2280 Kirchhof P, Benussi S, Kotecha D, et al 2016 ESC Guidelines for the management of atrial fibrillation development in collaboration with EACTS The Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC) Endorsed by the European Stroke Organisation (ESO) Eur Heart J 2016;37:2893-2962 doi:10.1093/eurheartj/ehw210 Whitlock RP, Sun JC, Fremes SE, et al Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines Chest 2012;141:e567S-e600S Nutescu EA, Shapiro NL, Chevalier A, et al A pharmacological overview of current and emerging anticoagulants Cleve Clin J Med 2005;72(Suppl 1):S2-S6 Connolly SJ, Ezekowitz MD, Yusuf S, et al; RE-LY Steering Committee and Investigators Dabigatran versus warfarin in patients with atrial fibrillation N Engl J Med 2009;361:1139-1151 Granger CB, Alexander JH, McMurray JV, et al; ARISTOTLE Committees and Investigators Apixaban versus warfarin in patients with atrial fibrillation N Engl J Med 2011;365:981-992 10 Giugliano RP, Ruff CY, Braunwald E, et al; ENGAGE AF-TIMI 48 Investigators Edoxaban versus warfarin in patients with atrial fibrillation N Engl J Med 2013;369:2093-2104 11 Patel MR, Mahaffey KW, Garg J, et al; ROCKET AF Investigators Rivaroxaban versus warfarin in nonvalvular atrial fibrillation N Engl J Med 2011;365:883-891 12 Apostolakis S, Lane D, Gao Y, Buller H, Lip GY Performance of the HEMORR2HAGES, ATRIA and HAS-BLED bleeding risk prediction scores in anticoagulated patients with atrial fibrillation: The AMADEUS study J Am Coll Cardiol 2012;60:861-867 13 Roldan V, Martin F, Fernandez H, et al Predictive value of the HAS-BLED and ATRIA bleeding scores for the risk of serious bleeding in a “real-world” population with atrial fibrillation receiving anticoagulant therapy Chest 2013;143(1):179-184 14 Gronberg T, Harika J, Nuotio I, et al Anticoagulation, CHA2DS2VASc score, and thromboembolic risk of cardioversion of acute atrial fibrillation (from the FinCV study) Am J Cardiol 2016;117:12941298 15 Lau Y, Proietti M, Guiducci E, et al Atrial fibrillation and thromboembolism in patients with chronic kidney disease J Am CollCardiol 2016;68(13):1452-1464 16 Schaefer JK, McBane RD, Wysokinski WE How to choose appropriate direct oral anticoagulant for patient with nonvalvular atrial fibrillation Ann Hematol 2016;95:437-449 17 Ageno W, Büller HR, Falanga A, et al Managing reversal of direct oral anticoagulants in emergency situations Anticoagulation Education Task Force White Paper Thromb Haemost 2016;116:1003-1010 doi:10.1160/TH16-05-0363 18 Pollack CV, Reilly PA, Eikelboom J, et al Idarucizumab for dabigatran reversal (RE-VERSE AD) N Engl J Med 2015;373:511-520 19 Connolly SJ, Milling TJ, Eikelboom JW, et al Andexanet alfa for acute major bleeding associated with factor Xa inhibitors (ANNEXA-4 study) N Engl J Med 2016;375:1131-1141 doi:10.1056/NEJMoa1607887 http://www.NEJM.org/doi/full/10.1056/NEJMoa1607887 Published August 30, 2016 Accessed July 11, 2017 20 Sarode RS, Milling TJ, Refaai MA, et al Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study Circulation 2013;128:1234-1243 21 Staerk L, Lip GYH, Olesen JB, et al Stroke and recurrent haemorrhage associated with antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation: nationwide cohort study BMJ 2015;351:h5876 22 Witt DM, Delate T, Garcia, DA, et al Risk of thromboembolism, recurrent hemorrhage, and death after warfarin therapy interruption for gastrointestinal tract bleeding Arch Intern Med 2012;172(19):14841491 23 Spyropoulos AC, Douketis JD How I treat anticoagulated patients undergoing an elective procedure or surgery Blood 2012;120(15):2954-2962 24 Bell BR, Spyropoulos AC, Douketis JD Perioperative management of the direct oral anticoagulants: a case-based review Hematol Oncol Clin North Am 2016;30:1073-1084 25 Douketis JD, Spyropoulos AC, Kaatz S, et al Perioperative bridging anticoagulation in patients with atrial fibrillation N Engl J Med 2015;373:823-833 26 Connolly SJ, Eikelboom J, Joyner C, et al; AVERROES Steering Committee and Investigators Apixaban in patients with atrial fibrillation N Engl J Med 2011;364:806-817 27 Hoshi T, Sato A, Nogami A, et al Rationale and design of the SAFE-A study: SAFety and Effectiveness trial of Apixaban use in association with dual antiplatelet therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention [published online ahead of print July 18, 2016] J Cardiol 2017;69:648-651 doi:10.1016/j.jjcc.2016.06.007 Patient and Family Information for: MODERN ANTICOAGULATION THERAPY ATRIAL FIBRILLATION AF is an irregular heart beat that increases the risk of forming a blood clot in the heart If the blood clot travels from the heart, it can cause a stroke Anticoagulants are medications that lower the chances of having a stroke by thinning the blood and therefore helping to prevent clots from forming A patient who stops taking the prescribed anticoagulant may have an increased risk of forming a clot in the heart and bloodstream Do not stop taking the prescribed anticoagulant without talking to the doctor who prescribed it Missing even one dose may increase the chances of forming a blood clot In case the anticoagulant medicine has to be stopped, be sure to tell the doctor TAKING ANTICOAGULANT MEDICATIONS Take medication exactly as prescribed by the doctor If the instructions are not clear, ask the doctor or pharmacist to explain • Do not change the dose or stop taking the anticoagulant unless the doctor says so • The doctor will tell how much medicine to take and when to take it • The doctor may change the dose if needed SIDE EFFECTS All medications have the potential to cause side effects, and anticoagulants are no exception There is a difference between an allergic reaction and a side effect Allergic reactions are types of side effects, for example, a rash, which usually means the patient never takes the medicine again Side effects, for example, bleeding or an upset stomach, due to an anticoagulant are usually dealt with simply by stopping the medication or changing to another similar alternative It is important to report any side effects the patient may think he or she is having and to get medical help right away if the patient thinks he or she is bleeding It is important to learn the signs or symptoms of bleeding Anticoagulants can cause bleeding in the brain that can be serious and can cause internal bleeding, which on rare occasions lead to death This is because anticoagulants are blood thinner medications that reduce blood clotting While on anticoagulants, the patient is likely to bruise more easily and it may take longer for the bleeding to stop Do not stop taking the anticoagulant without notifying the doctor on noticing bruising SIGNS AND SYMPTOMS OF BLEEDING Examples of unexpected bleeding or bleeding that lasts a long time may include the following: • Unusual bleeding from the gums • Nose bleeds that happen often • Menstrual bleeding that is heavier than normal or vaginal bleeding • Bleeding that is severe or cannot be controlled • Red, pink, or brown urine • Bright red or black tarry stools • Coughing up blood or blood clots • Vomiting blood or the vomit looks like “coffee grounds” • Headaches and feeling dizzy or weak • Pain, swelling, or new drainage at wound sites DRUG INTERACTIONS There is a chance that while on anticoagulants the patient may have a higher likelihood of bleeding if he or she takes other medicines that cause bleeding These medications may include aspirin or aspirin-containing products, clopidogrel (Plavix), prasugrel (Effient), ticagrelor (Brilinta), NSAIDs, SSRIs, SNRIs, or any other medicines to prevent or treat blood clots Inform the doctor about taking any of these medicines and ask the doctor or pharmacist if unsure whether the medicine is one among those listed earlier Also ask the doctor or pharmacist before taking any new medications, over-the-counter medications, vitamins, or herbal supplements SPINAL OR EPIDURAL BLOOD CLOTS People who take a blood thinner medicine and have an injection into their spinal and epidural area or have a spinal puncture have a risk of forming a blood clot that can cause long-term or permanent loss of the ability to move It is important to recognize the signs and symptoms of spinal or epidural blood clots if receiving spinal anesthesia or a spinal puncture Tell the doctor immediately in case of back pain, tingling, numbness, muscle weakness (especially in the legs and feet), and loss of control of the bowels or bladder (incontinence) Do not take an anticoagulant, without first talking to the doctor, under the following conditions: • If the patient has certain types of abnormal bleeding • If the patient is allergic to the prescribed medication or any of the ingredients; a pharmacist can help identify these ingredients What to tell the doctor before taking an anticoagulant medication: Inform the doctor about the following: • • • • • Bleeding problems Liver or kidney problems Any other medical condition Being pregnant or planning to become pregnant Breastfeeding or plan to breastfeed Tell the doctor about all the medicines the patient takes, including prescription and nonprescription medicines, vitamins, and herbal supplements Also inform all the doctors and dentists about taking an anticoagulant medication They should talk to the doctor who prescribed the anticoagulant before the patient has any surgery and medical or dental procedure How to take anticoagulant medications: • Take the medication exactly as prescribed by the doctor • Do not change the dose or stop taking the anticoagulant unless the doctor says so • The doctor will tell how much anticoagulant to take and when to take it • The doctor may change the dose if needed How to store anticoagulant medication: • Anticoagulant medications should be stored at room temperature between 68°F to 77°F (20°C to 25°C) • Be sure to keep all medicines out of the reach of children ... Description: Philadelphia: Wolters Kluwer Health, [2 018 ] | Includes bibliographical references and index Identifiers: LCCN 2 017 044559 | eISBN 97 814 963626 81 Subjects: | MESH: Heart Diseases | Critical Care Classification: LCC RC682 | NLM WG 210 | DDC 616 .1/ 2—dc23 LC record... Commerce Square, 20 01 Market Street, Philadelphia, PA 19 103, via e-mail at permissions@lww.com, or via our website at lww.com (products and services) 9 8 7 6 5 4 3 2 1 Printed in China Library of Congress Cataloging-in-Publication Data... Subjects: | MESH: Heart Diseases | Critical Care Classification: LCC RC682 | NLM WG 210 | DDC 616 .1/ 2—dc23 LC record available at https://lccn.loc.gov/2 017 044559 This work is provided “as is,” and the publisher disclaims any and all warranties, express or implied,