Intraoperative Off-Label Reversal of Apixaban by Andexanet Alfa while on VA-ECMO Immediately After Emergent Surgery for Acute Type A Aortic Dissection

The authors report a case of intraoperative reversal apixaban with andexanet alfa in patient supported venoarterial extracorporeal membrane oxygenation due to low- cardiac-output immediately after surgery for acute type A aortic dissection and massive transfusion administration procoagulants. In this patient, alfa's off-label use was not associated thrombotic complications despite being given during life support previous prothrombin complex concentrates. PRESCRIPTIONS OF direct oral anticoagulants are increasing constantly. It can be estimated that about 3% patients anticoagulated at some point will have undergo emergent procedures.1Garcia D Alexander JH Wallentin L et al.Management clinical outcomes treated vs warfarin undergoing procedures.Blood. 2014; 124: 3692-3698Crossref PubMed Scopus (114) Google Scholar Andexanet alfa, recombinant factor Xa without intrinsic activity, US Food Drug Administration–approved 2018 the inhibitors (eg, rivaroxaban) by high-affinity binding life-threatening bleeding. Its elimination half-life is 5-to-7 hours, its volume distribution approximately 5 L.2Heo YA alfa: First global approval.Drugs. 2018; 78: 1049-1055Crossref (65) Unfortunately, trials led approval drug excluded requiring urgent or surgery, which concentrates should considered as first-line agents.3Culbreth SE Rimsans J Sylvester K al.Andexanet alfa–The first 150 days.Am Hematol. 2019; 94: E21-E24Crossref (18) Some patients, however, already been before could delayed.4Culbreth KW al.Coordinating procedures alfa.Am E278-E282Crossref (4) Still, there currently no information available on either safety issues efficacy related when prior concentrate, has discouraged so far, (VA-ECMO). 69-year-old man (body weight: 162 kg, height: 189 cm) history hypertension chronic atrial fibrillation who had because while (5 mg twice day), last tablet taken 6 hours surgery. Apixaban's time peak effect 1-to-2 hours. reported onset chest pain shortness breath 15 hospital admission worsening symptoms he called an ambulance. His computed tomography angiography scan from peripheral infirmary showed extension level iliac arteries, whereby left renal artery perfused via false lumen. transthoracic echocardiograph performed transfer revealed moderate pericardial effusion. On presentation authors’ institution, apparent neurologic dysfunction. He alert fully oriented, slightly elevated respiratory rate oxygen saturation 94% O2/min facemask. heart 110/min 0.25 µg/kg/min norepinephrine support. Due high immediate mortality untreated dissection, delayed await natural clearance apixaban.5Bonser RS Ranasinghe AM Loubani M al.Evidence, lack evidence, controversy, debate provision performance dissection.J Am Coll Cardiol. 2011; 58: 2455-2474Crossref (146) During rapid-sequence induction, hemodynamics deteriorated quickly. Pericardial tamponade necessitated sternotomy. Evacuation effusion, together continuous vasopressors, bought surgeon anastomose vascular graft onto subclavian arterial cannulation. Venous access attained right femoral vein. Before going cardiopulmonary bypass, 47,500 units unfractionated heparin were administered achieve activated clotting >450 seconds. 74 minutes deep hypothermic circulatory arrest antegrade cerebral perfusion, ascending aorta hemi-aortic arch replacement carried out. secondary expansion into root only became release clamp, subsequent Bentall procedure performed. third cross-clamp necessary repair tear pulmonary artery. After 494 weaned high-dose pharmacologic VA-ECMO heparin-coated tubing implanted using same cannulation sites systemic reversed protamine 1:1 dose ratio followed attempt correct hemostasis. Despite whose core temperature ranging between 36.5°C 37°C having received 4.1 cell-saver blood, 13 packed red blood cells, 17 fresh frozen plasma, 4 platelet concentrates, 7 g fibrinogen, 3,500 IU concentrate (PCC), 30 µg desmopressin, 100 mL 10% calcium gluconate total, nonsurgical bleeding persisted such extent (800 infusion over 960 120 minutes) resort. Within initiation bolus infusion, coagulation loss, assessed clinically semiquantitatively, improved dramatically. course shown Figure 1, profiles depicted Table 1. 12-hour procedure, transferred intensive care unit open sternum, low-dose inotropic pressor support, ECMO flow 3.5 L/min. postoperative period, signs 24 1 cells given, cumulative drainage tubes mere 360 mL. Low-dose begun day (POD) day, hemodiafiltration initiated failure. POD 3, sternal vacuum-assisted closure system implanted. following day. Inotropic discontinued 10 sternum closed 15, insertion permanent pacemaker. prolonged weaning, surgical tracheostomy 18, vasopressors next Postoperative cranial small infarctions frontal lobe cerebellum described rather old injuries. When awake, able move both his legs remained paraplegic. magnetic resonance imaging spinal cord ventral ischemic damage below seventh thoracic vertebra compatible anterior syndrome. iwas sound mind, gave written informed consent publication course.Table 1Coagulation Profile Surgery Postoperatively Massive Transfusion, Replacement Coagulation Factors, Administration AlfaLaboratory Test (unit)PreoperativePostoperativeReference RangePlatelets (G/L)12554150-350PT (%)456370-125INR1.51.2aPTT (sec)386827-41Anti-Xa LMWH (IU/mL)1.870.34<0.10Fibrinogen (mg/dL)302197200-400INTEM CT (sec)188359100-240INTEM CFT (sec)11323430-110INTEM ?-angle (°)685444-66Abbreviations: anti-Xa LMWH, anti-factor activity low–molecular-weight heparin; aPTT, partial thromboplastin time; CFT, clot formation INR, international normalized ratio; INTEM CT, (thromboelastometry study); PT, time. Open table new tab Abbreviations: observation demonstrated even emergent, prolonged, complicated comprising cardiac arrest, inadequate conventional hemostatic treatment, reverse sustained anticoagulant immediately, presumably clearance. earlier PCC, management caused neither hemolysis nor thrombus within oxygenator VA-ECMO. sole factors, specifically generally recommended situations like these, capable reinstitute sufficient early reversal, Culbreth al.,3Culbreth possible hemodynamically unstable situation encountered soon anesthesia induction stabilizing bypass Additionally, PCC preoperatively lead unpredictable status resistance fact also reverses indirect Xainhibitors. This interaction requires excessive doses reach targeted heart-lung machine, incision.6Flaherty Connors JM Singh S bypass: report.A Pract. 13: 271-273Crossref Using regimen 20 U/kg other procoagulants is, risks—not mention horrendous costs (approximately $50,000) it. Postrepletion hypercoagulation, consecutive thromboembolic complications, serious concern still normal circulating X.7Gibler WB Racadio Hirsch AL Roat TW Management severe anticoagulants: Proceedings monograph Emergency Medicine Cardiac Research Education Group-International Multidisciplinary Severe Bleeding Consensus Panel October 20, 2018.Crit Pathw 18: 143-166Crossref (12) Nevertheless, opted favor it rescue therapy risk insufficient control judged clearly outweighing thrombosis point. further assumed might impeded kidney perfusion hypothermia. Postoperatively, (calibrated heparins) but dropped significantly (Table 1), plasmatic completely. infarction feared complication aorta.5Bonser Paraplegia pronounced atherosclerosis, most likely attributable impaired perfusion. However, cannot rule out may aggravated embolic luminal narrowing arteries under pre-existing limitations, result procoagulants.8Andexxa - An antidote rivaroxaban.JAMA. 320: 399-400Crossref (8) porcine polytrauma model, merely antagonized causing overactivation fibrinolysis.9Grottke O Braunschweig T Rossaint R al.Transient extended anticoagulation equally effective model.Br Anaesth. 123: 186-195Abstract Full Text PDF Anticoagulation, inhibitors, does require monitoring. viscoelastic bedside tests studies calibrated heparins provide limited degree specific assays routinely optimize treatment those major spontaneous bleeding.7Gibler None.