Amicar (contact pharmacy (adult dose=15ml/kg) Administration /Miscellaneous single adult single plasmaadult dose= 10-15ml/kg plasma can plasma be used if is 4FPCC unavailable. FFP 2 or may require more adult dosesfor total reversalmayexceed and 6 hours PlasmaConsider o o FFP: IfINR remains elevatedsingle post dose theand/or isstill patient experiencing uncontrolled bleeding, redosing ofcan PCCbe considered. Max dose is 5000 Redosingunits. K ofVitamin is rarely indicated, but may be12 given after hoursof original dose. IV minsslowly~over 10 Beware anaphylactoidreaction;>50mg/dose See UFH care;Supportivecomponents,blood factor (Kcentra4 PCC )contains 25units/kg interventionsIfnotinitial control bleeding, do consider: forPlatelet > 50 major count surgery/100kfor neurosurgical/ophthalmic. DDAVP mcg/kg0.3 in 50mlNS mins over15-30 Platelet transfusions have shownbeen not improve to outcomes; clinical however, recommendations the provided are based on the recent most neuro/critical care guidelines. with repeat dose of 25 units/kg(max 5000 5000 units) of 25 units/kg(max dose repeat with use IfTXA contraindicated- fordosing) mg/dl 150 Keepfibrinogen> 50mg iai 0m IV vitamin Kmg 10 PLUS 0.3 mcg/kg IV 0.3mcg/kg x 1

off label-but optionoff is label-but an in threateninglife Reversal Recommendation Reversal (1adult 5 pooleddose = units) (max 5000 units; Hold theanticoagulant. Consider laboratory additional analysis PCC 4 factorPCC(Kcentra) 4 1500 IVunits (single adultdose= 1unit)(single Phytonadione K)(Vitamin IV10 mg over30 minutes .) Vit K K Vit ALONE can significantly reversethewithin INR to change 6-8 should so hours) be sole considered agentif as intervention no is needed time. until that Dosemay(max be repeated 5000 units) o o Non-urgent: on INR. 1 based mgx PO Consider KVitamin 10 reassessand bleeding risks. Urgent: Emergent: over minutes 30 max dose= mins; 10 of IV heparin infusedover protamine/1001mg units repeating calculated to amount protamine give 1mg 8hrs; protamine/mg Activity 60% neutralized< by protamine; give protamine/1mg 0.5mg enoxaparin - 8hrs > Lastenoxaparin. dose Second dose needed: after0.5mg hrs ofenoxaparinprotamine/1mg thefirst.2-4 None thefollowing(None of products has shownreducebeen to bleeding in these however,pts; antidote is nodirect therefor ) over 8 hours followedby gtt 1gm IVTXA 1gm over bolus 10 mins dose 1 Cryoprecipitate Platelets Vitamin is K NOT effective careSupportive factor (Kcentra4 25 PCC dose of repeat heparin)contains 25 with units/kg Platelets with single Start unit (single unit= 1 adult dose) plateletUtility of transfusioncritical in bleeding remainspatients under investigation. DDAVP overload)(caution: fluid Idarucizumab 5g, each providedcontaining two2.5g/50ml;as vials separate giveonethe after other. Limited data administrationsupports ofan additional of(Praxbind)5g idarucizumab units/kg if if needed units/kg situation & Anticoagulant AntiplateletReversal Medication 1: Identify the Identify 1: StopmedicationConfirmmedication the 2: time 3: of dose last days Half-life (t1/2)Half-life 13 hrs 13 21 hours21 - -2hs~ upon renal 7-12 hrs function 17 ~5min & 5-9 elderlyhrs 11- 1) 8-15 hrs 2) 9-11 hrs 3) 19-25 hrs 4) ~6 hrs 1) ~7 hrs 2) ~7 hrs 3) ~8 4) (t1/2=12-17 hours but longerrenalmuch with impairment) : Xa; - Monitor hoursor greater oeta nevninwti -2hours: 6-12 within potentialintervention 24 Immediateaction needed: - /INRless(if normal, 12 Monitor PT/INR 20-60 hrs Determine risk (emergent, Determinerisk for appropriateurgent, non-urgent intervention) hrs 20-60 PT/INR Monitor minutes 90 aPTT Platelets aPTT anti-Xa;Monitor platelets plateletsMonitor anti thrombocytopenia is rare. neurologicMonitor aPTT,exam; PTand fibrinogen, platelets. PT likely drug that is contributing ongoingto bleeding) bleeding,Monitor Hct, testing. function platelet APTT:less(if normal, likely drug that is contributing ongoingto bleeding) - ) ) 12 ) 12 12 : oral bleeding patientbleeding - Heparin (UFH);Heparin enoxaparin fondaparinux recombinant non - ulant: Drug: AgentType Drug: Revised 4-2020 Revised Feb 22, 2018 Page 1 Page Reversal Medication Deaconess Anticoagulant Antiplatelet &sheet cheat Protocol 201822, Feb urgent - Emergent- Life threatening Life bleeding- Emergent- necessary values and if baseline therapy. modifyto Therapy the may to be prior initiated lab (seebelow) table Considerlaboratory analysis for Hold specificgivingand consider a and/or apro-coagulantantidote agent being results posted bleeding- Urgent-non-life-threatening anticoagulantshold and considerspecificgivinga and/orantidote aagentpro-coagulant(see table below)Consider laboratory analysis and if values for necessarybaseline modify to therapy.the Non anticoagulant.Hold the additionalConsider laboratoryanalysisreassess and bleedingrisks. Vitamin antagonist:K factorsCoagulation II, IX,VII, anticoagulant X; proteins C, S Anticoagulant: to binds ; Xa;IIa; inactivates inactivates thrombinindirect inhibitor Anticoagulant: (Lovenox;LMWH); to binds antithrombin; inactivates Xa Anticoag (Arixtra); bindsto antithrombin; Xa; inactivates a . Thrombolytic: plasminogentissue activator XaFactor inhibitor (Xarelto) 1. (Eliquis) 2. (Savaysa) 3. (Bevyxxa) 4. platelet Oral inhibitors: P2Y (Plavix- 1. -P2Y (Effient 2. (Brilinta-P2Y 3. (Zontivity Vorapaxar -Par1) 4. thrombinDirect inhibitor: (oral) (Pradaxa)

Circulation

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Reversal ofrivaroxaban and dabigatranconcentrate: prothrombinby a placebo-controlled, randomized, complex study crossover healthy in subjects. Individualized dosingregimenfor prothrombin concentratecomplex effectivemore thantreatment standardtherapy:theanticoagulant in reversalof oral An Safetyof prothrombin complex concentrateforrapid anticoagulation reversalof vitamin anticoagulation:K meta-analysis. A

ThrombosisResearch. 313-320. 118: 2006; . Reversal. theofofinhibitory fondaparinuxeffect on generationaPCC by andrFVIIa, PCC. The The effectivenessand fixedsafety of lowprothrombin dose complex concentrates patientsin requiringurgentreversalof . versusFixedvariable dose prothrombinofcomplex concentrate for counteracting antagonistvitamin K therapy. forGuidelinesreversalof intracranialinhemorrhage. A systematicA of review prothrombin complex concentrate dosingstrategiesto vitamin reverse antagonistK therapy. Managementof non-vitamin patients on antagonistK oral anticoagulants inthe andacute care periprocedural setting: Heart scientific a statement from the American Edoxabanoneffects bleeding following biopsypunch prothrombinanda complex4-factor reversal by concentrate. Evaluation doseof fixed 4-factorprothrombin complex concentrate warfarinfor emergent reversal. An observational, An prospective, comparison two-cohort ofdosingfixed variable a versus strategy prothrombinof concentratecomplex to counteract antagonistsvitamin K in 240 Prothrombin Complexconcentratesbleeding forin the perioperative setting Bleedingrisk and the managementof bleeding complicationsin patients undergoing anticoagulant agents. therapy: anticoagulant focusnew on Administrationof 4-factorprothrombin concentratecomplex an as antidotefor bleedingintracranial patients in taking factor direct inhibitors. Xa Haematologica 2012; 97: 97: 2012; 1501-1506. Haematologica

. Activated. prothrombin complex of concentrates thefor anticoagulant-associated reversal coagulopathy. Circulation.2017; 135: e604-e633. 135: Circulation.2017;

Desmurs-Clavel H, Desmurs-ClavelHuchonC, ChatardH, etB, al Crowther WarkentinMA, TE. Zahir VandellBrown H, KS, et AG, al. Kamphuisen Eerenberg ES, PW, Sijpkens et al. MK, 124: 1573-1579.2011; Zhang etNewman WC, X, al. 1961. Levy Ghadimi Welsby K, JH, IJ. NI, Awad Cocchio C RavalCigarroaChunget JE, AN, MK, al. Association. Klein PetersL, J, J,Miner Gorlin J. Dentali Pierfranceschi MarcheslC, F, etMG, al. 438. C, Varga Al-TouriPapadoukakis S, et S, al. Khorsand N, VeegerNJGM,Muller et al. M, van KamphuisAart Eijkhout JanL, S. HW, et al.JS, open, prospective randomized trial.controlled Khorsand N, VeegerNJGM,et al. bleeding emergencies. Khorsand N, Kooistra van Hest HAM, RM. Frontera Lewin JA, JJ,Rabenstein et al.AA etS al.Yaghi Treatment and outcomeof hemorrhagictransformation intravenousafter e343-e361. 48: inacutestroke.2017; altepase ischemic Stroke Powers RabinsteinWJ, AckersonAdeoye T, AA, BambakidisOM, BillerK, J, BrownDemaerschalk M, NC,Becker Leslie-MazwiCS,Hoh B, OvbiageleJauch TM, BM, Kidwell B, Sheth EC, Scott SoutherlandPA, KN, DV, AM,Summers Tirschwell onDL; behalfof theAmerican Association Stroke Council.Heart Guidelines 2018 theearlyfor management acuteischemic stroke: patients ofa healthcareguideline with for professionalsfrom the American Association/AmericanHeart Stroke Association. Stroke. 2018;49:eXXX

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