Rivaroxaban-Associated Intraparenchymal Hemorrhage Managed with 4-Factor Prothrombin Complex Concentrate

Purpose of Review Background: Rivaroxaban is a Xa inhibitor and one of the direct acting oral anticoagulants (DOAC) that currently does not have evidence-based guidelines for its reversal. Prothrombin complex concentrate (PCC) has been recommended as a potential reversal agent for life-threatening b...

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Published in:Current emergency and hospital medicine reports Vol. 6; no. 2; pp. 62 - 68
Main Authors: Patel, Jayme S. K., Rahbar, Aryan J., Patel, Ketan, Sigal, Tiffany W.
Format: Journal Article
Language:English
Published: New York Springer US 01.06.2018
Springer Nature B.V
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ISSN:2167-4884, 2167-4884
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Abstract Purpose of Review Background: Rivaroxaban is a Xa inhibitor and one of the direct acting oral anticoagulants (DOAC) that currently does not have evidence-based guidelines for its reversal. Prothrombin complex concentrate (PCC) has been recommended as a potential reversal agent for life-threatening bleeds. With no direct antidote and its widespread usage, the attempt to manage life-threatening hemorrhages with procoagulant drugs will continue to rise. Recent Findings Case report :A 55-year-old male on rivaroxaban and clopidogrel presented to another facility with ataxia, confusion, and lateralizing weakness. Computed tomography (CT) scan of the brain showed a large intraparenchymal hemorrhage. He was intubated, given mannitol and nicardipine, and transferred to our tertiary care facility. His coagulation studies upon arrival were normal. He was given 50 units/kg of PCC in an attempt to reverse rivaroxaban and one unit of platelets for clopidogrel reversal. A repeat CT 18 h later showed extension of the bleed. Neurosurgical intervention was not done, and 4 days into his stay, a right cephalic vein thrombosis was found. During his hospital stay, the patient developed encephalopathy and required a tracheostomy tube and gastrostomy tube. A CT on day 36 showed stabilization of the bleeds, and on day 42, he was transferred to a skilled nursing facility. Summary Why should an emergency physician be aware of this? Novel oral anticoagulants are becoming ever popular due to their ease in management and lack of required monitoring when compared to conventional therapy. But, they are still associated with hemorrhages, which is their most common complication. Due to the lack of antidotes and reversal agents for DOACs, prothrombotic agents are being frequently utilized in the setting of life-threatening hemorrhages. While various case reports have been published on the usage of varying dosages of PCC to treat rivaroxaban-associated bleeds, no strong evidence exists to its clinical efficacy. Our case adds to the growing body of evidence showing a lack of clinical efficacy in the reversal of the anticoagulation effects of oral factor Xa inhibitors in addition to a complication in utilizing this potential reversal agent (J Crit Care 33:252–6, 2016; J Thromb Heamost 12:1428–1436, 2014; World Neurosurg 84(6)1956–1961, 2015)
AbstractList Purpose of ReviewBackground: Rivaroxaban is a Xa inhibitor and one of the direct acting oral anticoagulants (DOAC) that currently does not have evidence-based guidelines for its reversal. Prothrombin complex concentrate (PCC) has been recommended as a potential reversal agent for life-threatening bleeds. With no direct antidote and its widespread usage, the attempt to manage life-threatening hemorrhages with procoagulant drugs will continue to rise.Recent FindingsCase report :A 55-year-old male on rivaroxaban and clopidogrel presented to another facility with ataxia, confusion, and lateralizing weakness. Computed tomography (CT) scan of the brain showed a large intraparenchymal hemorrhage. He was intubated, given mannitol and nicardipine, and transferred to our tertiary care facility. His coagulation studies upon arrival were normal. He was given 50 units/kg of PCC in an attempt to reverse rivaroxaban and one unit of platelets for clopidogrel reversal. A repeat CT 18 h later showed extension of the bleed. Neurosurgical intervention was not done, and 4 days into his stay, a right cephalic vein thrombosis was found. During his hospital stay, the patient developed encephalopathy and required a tracheostomy tube and gastrostomy tube. A CT on day 36 showed stabilization of the bleeds, and on day 42, he was transferred to a skilled nursing facility.SummaryWhy should an emergency physician be aware of this? Novel oral anticoagulants are becoming ever popular due to their ease in management and lack of required monitoring when compared to conventional therapy. But, they are still associated with hemorrhages, which is their most common complication. Due to the lack of antidotes and reversal agents for DOACs, prothrombotic agents are being frequently utilized in the setting of life-threatening hemorrhages. While various case reports have been published on the usage of varying dosages of PCC to treat rivaroxaban-associated bleeds, no strong evidence exists to its clinical efficacy. Our case adds to the growing body of evidence showing a lack of clinical efficacy in the reversal of the anticoagulation effects of oral factor Xa inhibitors in addition to a complication in utilizing this potential reversal agent (J Crit Care 33:252–6, 2016; J Thromb Heamost 12:1428–1436, 2014; World Neurosurg 84(6)1956–1961, 2015)
Purpose of Review Background: Rivaroxaban is a Xa inhibitor and one of the direct acting oral anticoagulants (DOAC) that currently does not have evidence-based guidelines for its reversal. Prothrombin complex concentrate (PCC) has been recommended as a potential reversal agent for life-threatening bleeds. With no direct antidote and its widespread usage, the attempt to manage life-threatening hemorrhages with procoagulant drugs will continue to rise. Recent Findings Case report :A 55-year-old male on rivaroxaban and clopidogrel presented to another facility with ataxia, confusion, and lateralizing weakness. Computed tomography (CT) scan of the brain showed a large intraparenchymal hemorrhage. He was intubated, given mannitol and nicardipine, and transferred to our tertiary care facility. His coagulation studies upon arrival were normal. He was given 50 units/kg of PCC in an attempt to reverse rivaroxaban and one unit of platelets for clopidogrel reversal. A repeat CT 18 h later showed extension of the bleed. Neurosurgical intervention was not done, and 4 days into his stay, a right cephalic vein thrombosis was found. During his hospital stay, the patient developed encephalopathy and required a tracheostomy tube and gastrostomy tube. A CT on day 36 showed stabilization of the bleeds, and on day 42, he was transferred to a skilled nursing facility. Summary Why should an emergency physician be aware of this? Novel oral anticoagulants are becoming ever popular due to their ease in management and lack of required monitoring when compared to conventional therapy. But, they are still associated with hemorrhages, which is their most common complication. Due to the lack of antidotes and reversal agents for DOACs, prothrombotic agents are being frequently utilized in the setting of life-threatening hemorrhages. While various case reports have been published on the usage of varying dosages of PCC to treat rivaroxaban-associated bleeds, no strong evidence exists to its clinical efficacy. Our case adds to the growing body of evidence showing a lack of clinical efficacy in the reversal of the anticoagulation effects of oral factor Xa inhibitors in addition to a complication in utilizing this potential reversal agent (J Crit Care 33:252–6, 2016; J Thromb Heamost 12:1428–1436, 2014; World Neurosurg 84(6)1956–1961, 2015)
Author Patel, Jayme S. K.
Rahbar, Aryan J.
Patel, Ketan
Sigal, Tiffany W.
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  surname: Sigal
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  organization: Department of Emergency Medicine, UNLV School of Medicine
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Cites_doi 10.1007/s00392-013-0560-7
10.1160/TH12-03-0179
10.1111/jth.12599
10.1016/j.jemermed.2013.03.016
10.1160/TH12-12-0907
10.1016/j.ajem.2014.01.042
10.1093/eurheartj/ehs408
10.1056/NEJMoa0905561
10.1097/ALN.0b013e318238c036
10.1056/NEJMoa1007903
10.1016/j.ajem.2013.11.044
10.1016/j.jemermed.2016.11.011
10.1056/NEJMoa0800374
10.1056/NEJMoa1302507
10.1111/jth.12236
10.1016/j.thromres.2014.01.017
10.1056/NEJMoa1607887
10.1016/S0140-6736(08)60880-6
10.1177/1076029613494468
10.1002/phar.1270
10.1136/postgradmedj-2016-134486
10.1007/s11936-013-0238-5
10.2146/ajhp150810
10.3949/ccjm.80a.13025
10.1056/NEJMc1411800
10.1016/j.jcrc.2016.02.018
10.1016/j.jacc.2014.05.065
10.1056/NEJMoa1107039
10.1056/NEJMoa1306638
10.1016/j.wneu.2015.08.042
10.1056/NEJMoa1510991
10.1016/j.acvd.2013.04.009
10.1007/s40262-013-0100-7
10.1056/NEJMoa1009638
10.1586/erc.11.62
10.1056/NEJMoa1113572
10.1161/CIRCULATIONAHA.113.004450
10.1161/CIRCULATIONAHA.111.029017
10.2146/ajhp130041
10.1016/j.ajem.2014.01.049
10.1056/NEJMoa076016
10.1161/STROKEAHA.112.675231
10.1016/j.cjca.2014.01.015
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Keywords Rivaroxaban
PCC
Kcentra
Intraparenchymal hemorrhage
Prothrombin complex concentrate
Intracerebral hemorrhage
ICH
Anticoagulant reversal
Language English
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References PerzbornEHeitmeierSLauxVBuchmüllerAReversal of rivaroxaban-induced anticoagulation with prothrombin complex concentrate, activated prothrombin complex concentrate and recombinant activated factor VII in vitroThromb Res201413367168110.1016/j.thromres.2014.01.017
SiegalDCurnutteJConnollySAndexanet alfa for the reversal of factor Xa inhibitor activityN Engl J Med2015373241324241:CAS:528:DC%2BC28XitFc%3D10.1056/NEJMoa151099126559317
GonzvaJPatricelliRLignacDSpontaneous splenic rupture in a patient treated with rivaroxabanAm J Emerg Med201432950.e310.1016/j.ajem.2014.01.04924612597
AgnelliGBullerHRCohenACurtoMGallusASJohnsonMMasiukiewiczUPakRThompsonJRaskobGEWeitzJIAMPLIFY InvestigatorsOral apixaban for the treatment of acute venous thromboembolismN Engl J Med20133697998081:CAS:528:DC%2BC3sXhtlyis7fN10.1056/NEJMoa130250723808982
Hokusai-VTE InvestigatorsEdoxaban versus warfarin for the treatment of symptomatic venous thromboembolismN Engl J Med20133691406141510.1056/NEJMoa1306638
SchulmanSKakkarAKGoldhaberSZSchellongSErikssonHMismettiPChristiansenAVFriedmanJle MaulfFPeterNKearonCfor the RE-COVER II Trial Investigators*Treatment of acute venous thromboembolism with dabigatranCirculation20141297647721:CAS:528:DC%2BC2cXjtlSnsr0%3D10.1161/CIRCULATIONAHA.113.00445024344086
MueckWStampfussJKubitzaDBeckaMClinical pharmacokinetic and pharmacodynamic profile of rivaroxabanClin Pharmacokinet20145311161:CAS:528:DC%2BC2cXksVaktw%3D%3D10.1007/s40262-013-0100-723999929
KaatzSKouidesPAGarciaDAGuidance on the emergent reversal of oral thrombin and factor 317 Xa inhibitorsAm J Hematol201289S414S145
PernodGAlbaladejoPGodierASamamaCMSusenSGruelYBlaisNFontanaPCohenALlauJVRosencherNSchvedJFde MaistreESamamaMMMismettiPSiéPWorking Group on Perioperative HaemostasisManagement of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor Xa 320 inhibitors: proposals of the Working Group on Perioperative Haemostasis (GIHP) – March 2013Arch Cardiovasc Dis201310638239310.1016/j.acvd.2013.04.00923810130
SteinerTBohmMDichgansMRecommendations for the emergency management of complications associated with the new direct oral anticoagulants (DOACs), apixaban, dabigatran, and rivaroxabanClin Res Cardiol20131023994121:CAS:528:DC%2BC3sXnvFSqt7s%3D10.1007/s00392-013-0560-723669868
CukerASiegalDCrowtherMLaboratory measurement of the anticoagulant activity of the non-vitamin K oral anticoagulantsJ Am Coll Cardiol201464112811391:CAS:528:DC%2BC2cXhsFerurjL10.1016/j.jacc.2014.05.065252126484167772
MaoGKingLYoungSKaplanRFactor eight inhibitor bypassing agent (FIEBA) for reversal of target specific oral anticoagulants in life-threatening intracranial bleedingJ EmergMed201752573173710.1016/j.jemermed.2016.11.011
GrangerCBAlexanderJHMcMurrayJLopesRDHylekEMHannaMal-KhalidiHRAnsellJAtarDAvezumABahitMCDiazREastonJDEzekowitzJAFlakerGGarciaDGeraldesMGershBJGolitsynSGotoSHermosilloAGHohnloserSHHorowitzJMohanPJanskyPLewisBSLopez-SendonJLPaisPParkhomenkoAVerheugtFWZhuJWallentinLARISTOTLE Committees and InvestigatorsApixaban versus warfarin in patients with atrial fibrillationN Engl J Med20113659819921:CAS:528:DC%2BC3MXhtF2ms7rN10.1056/NEJMoa110703921870978
AgenoWGallusASWittkowskyAOral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice GuidelinesChest20122Supple445e885
ErikssonBIBorrisLCFriedmanRJHaasSHuismanMVKakkarAKBandelTJBeckmannHMuehlhoferEMisselwitzFGeertsWRECORD1 Study GroupRivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplastyN Engl J Med2008358276527751:CAS:528:DC%2BD1cXnvFahtbo%3D10.1056/NEJMoa080037418579811
EerenbergESKamphuisenPWSijpkensMKReversal of rivaroxaban and dabigatran by 337 prothrombin complex concentrate. A randomized, placebo-controlled, crossover study in healthy 338 subjectsCirculation2011124157315791:CAS:528:DC%2BC3MXht1GjsLfO10.1161/CIRCULATIONAHA.111.02901721900088This study reports a complete reversal of elevated prothrombin time (PT) and normalization of endogenous thrombin potential (ETP) following administration of 4-factor PCC in humans given rivaroxaban. In summary, this study provides evidence for successful reversal of rivaroxaban with 4-factor PCC via markers of PT and ETP.
GrandhiRNewmanCZhangXAdministration of 4-factor prothrombin complex concentrate as in antidote for intracranial bleeding in patients taking direct factor Xa inhibitorsWorld Neurosurg20158461956196110.1016/j.wneu.2015.08.04226341438
PerzbornEGruberATinelHMarzecUMBuetehornUBuchmuellerAHeitmeierSLauxVReversal of rivaroxaban anticoagulation by haemostatic agents in rats and primatesThromb Haemost20131101621721:CAS:528:DC%2BC3sXhtFKls7jL10.1160/TH12-12-090723636219
AnsellJBakhruSLaulichtBUse of PER977 to reverse the anticoagulant effect of edoxabanN Engl J Med20143712141214210.1056/NEJMc141180025371966
SiegalDMCrowtherMAAcute management of bleeding in patients on novel oral anticoagulantsEur 313 Heart J2013344895001:CAS:528:DC%2BC3sXivFaqtLk%3D10.1093/eurheartj/ehs408
PatelMRMahaffeyKWGargJRivaroxaban versus warfarin in nonvalvular atrial fibrillationN 302 Engl J Med20113658838911:CAS:528:DC%2BC3MXhtFKhsLnI10.1056/NEJMoa1009638
KakkarAKBrennerBDahlOEErikssonBIMouretPMuntzJSoglianAGPapÁFMisselwitzFHaasSExtended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomized controlled trialLancet200837231391:CAS:528:DC%2BD1cXotlWqsrg%3D10.1016/S0140-6736(08)60880-618582928
RileyTGauthier-LewisMSanchezCRole of agents for reversing the effects of target-specific oral anticoagulantsAm J Health-Syst Pharm2017742546110.2146/ajhp15081027895055This article looked at the various different mechanisms for reversing oral anticoagulants. It also reviewed the latest information on the new reversal agents that are still currently in early trials, but may show some promising effects for reversing oral anticoagulants, especially factor Xa inhibitors.
FawoleADawHACrowtherMAPractical management of bleeding due to the anticoagulants dabigatran, rivaroxaban, and apixabanCleve Clin J Med21038044345110.3949/ccjm.80a.13025
PollackCVManaging bleeding in anticoagulated patients in the emergency care settingJ Emerg Med20134546747710.1016/j.jemermed.2013.03.01623786779
KalusJSPharmacologic interventions for reversing the effects of oral anticoagulantsAm J Health-Syst Pharm201370S12S211:CAS:528:DC%2BC3sXptVWqtrY%3D10.2146/ajhp13004123640528
AkwaaFSpyropoulosACTreatment of bleeding complications when using oral anticoagulants for 332 prevention of strokesCurr Treat Options Cardiovasc Med20131528829810.1007/s11936-013-0238-523494907
LassenMRAgenoWBorrisLCLiebermanJRRosencherNBandelTJMisselwitzFTurpieAGRECORD3 InvestigatorsRivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplastyN Engl J Med2008358277627861:CAS:528:DC%2BD1cXnvFagt70%3D10.1056/NEJMoa07601618579812
LeviMMooreKCastillejosCComparison of three-factor and four-factor prothrombin complex concentrates regarding reversal of the anticoagulant effects of rivaroxaban in healthy volunteersJ Thromb Heamost201412142814361:CAS:528:DC%2BC2cXhsFCjurzP10.1111/jth.12599This study was unable to completely reverse the PT as described in the Eerenberg study. In addition, 4-factor PCC did not produce as robust of a reversal of ETP that 3-factor PCC did. Both 3-factor and 4-factor PCC did not have an effect on activated partial thromboplastin time (APTT). In summary, this study presents evidence for a more muted response to PCC as compared to the Eerenberg study.
ZhouWZornMNawrothPButehornUPerzbornEHeitmeierSVeltkampRHemostatic therapy in experimental intracerebral hemorrhage associated with rivaroxabanStroke2013447717781:CAS:528:DC%2BC3sXms1ylt70%3D10.1161/STROKEAHA.112.67523123339956
The EINSTEIN InvestigatorsOral rivaroxaban for symptomatic venous thromboembolismN Engl J Med20103632499251010.1056/NEJMoa1007903
MarluRHodajEParisAAlbaladejoPCrackowskiJPernodGEffect of non-specific agents on anticoagulant activity of dabigatran and rivaroxabanThromb Haemost20121082172241:CAS:528:DC%2BC38Xht1GitbrN10.1160/TH12-03-017922627883
EINSTEIN InvestigatorsOral rivaroxaban for sympotomatic venous thromboembolismN Engl J Med20103632499251010.1056/NEJMoa1007903
MangramAOguntoduODzanduJIs there a difference in efficacy, safety and cost-effectiveness between 3-factor and 4-factor prothrombin complex concentrates among trauma patients on oral anticoagulants?J Crit Care2016332522561:CAS:528:DC%2BC28Xks1yksbg%3D10.1016/j.jcrc.2016.02.01827021851
MillerMPTrujilloTCNordenholzKEPractical considerations in emergency management of bleeding in the setting of target-specific oral anticoagulantsAm J Emerg Med20143237538210.1016/j.ajem.2013.11.04424512886
RomualdiEDonadiniMPAgenoWOral rivaroxaban after symptomatic venous thromboembolism: the continued treatment study (EINSTEIN-extension study)Expert Rev Cardiovasc Ther201198418441:CAS:528:DC%2BC3MXps1ygt78%3D10.1586/erc.11.6221809964
KnepperJHorneDObiAWakefieldTWA systemic update on the state of novel anticoagulants a primer on reversal and bridgingJ Vasc Surg: Venous and Lym Dis20131418426
ConnollySJEzekowitzMDYusufSEikelboomJOldgrenJParekhAPogueJReillyPAThemelesEVarroneJWangSAlingsMXavierDZhuJDiazRLewisBSDariusHDienerHCJoynerCDWallentinLRE-LY Steering Committee and InvestigatorsDabigatran versus warfarin in patients with atrial fibrillationN Engl J Med2009361113911511:CAS:528:DC%2BD1MXhtFOjsLnN10.1056/NEJMoa090556119717844
KörberMLangerEZiemerSMeasurement and reversal of prophylactic and therapeutic peak levels of rivaroxaban: an in vitro studyClin Appl Thromb Hemost20142073574010.1177/107602961349446823832064
ConnollySMillingTEikelboomJANNEXA-4 investigators. Adenanet alfa for acute major bleeding associated with the factor XA inhibitorsN Engl Med2016375113111411:CAS:528:DC%2BC28XhvF2ksrnM10.1056/NEJMoa1607887
ThigenJLLimdiNAReversal of oral anticoagulati
Hokusai-VTE Investigators (157_CR14) 2013; 369
A Cuker (157_CR31) 2014; 64
G Agnelli (157_CR13) 2013; 369
J Dinkelaar (157_CR33) 2013; 11
SJ Connolly (157_CR9) 2009; 361
F Akwaa (157_CR27) 2013; 15
157_CR1
BI Eriksson (157_CR2) 2008; 358
DM Siegal (157_CR19) 2013; 34
S Connolly (157_CR47) 2016; 375
D Siegal (157_CR46) 2015; 373
T Riley (157_CR44) 2017; 74
JL Thigen (157_CR26) 2013; 33
S Balla (157_CR30) 2017; 93
MR Patel (157_CR6) 2011; 365
W Mueck (157_CR15) 2014; 53
CV Pollack (157_CR18) 2013; 45
R Marlu (157_CR34) 2012; 108
CB Granger (157_CR10) 2011; 365
ES Eerenberg (157_CR32) 2011; 124
G Pernod (157_CR22) 2013; 106
R Grandhi (157_CR29) 2015; 84
M Körber (157_CR36) 2014; 20
S Kaatz (157_CR21) 2012; 89
W Zhou (157_CR37) 2013; 44
J Knepper (157_CR28) 2013; 1
E Perzborn (157_CR35) 2014; 133
The EINSTEIN-PE Investigators (157_CR8) 2012; 366
W Ageno (157_CR17) 2012; 2
EINSTEIN Investigators (157_CR12) 2010; 363
A Fawole (157_CR24) 2103; 80
S Schulman (157_CR11) 2014; 129
A Mangram (157_CR16) 2016; 33
JS Kalus (157_CR23) 2013; 70
157_CR41
J Gonzva (157_CR42) 2014; 32
157_CR45
A Godier (157_CR39) 2012; 116
AK Kakkar (157_CR3) 2008; 372
T Steiner (157_CR25) 2013; 102
M Levi (157_CR40) 2014; 12
The EINSTEIN Investigators (157_CR7) 2010; 363
MP Miller (157_CR20) 2014; 32
G Mao (157_CR43) 2017; 52
J Ansell (157_CR48) 2014; 371
E Romualdi (157_CR5) 2011; 9
E Perzborn (157_CR38) 2013; 110
MR Lassen (157_CR4) 2008; 358
References_xml – reference: ZhouWZornMNawrothPButehornUPerzbornEHeitmeierSVeltkampRHemostatic therapy in experimental intracerebral hemorrhage associated with rivaroxabanStroke2013447717781:CAS:528:DC%2BC3sXms1ylt70%3D10.1161/STROKEAHA.112.67523123339956
– reference: MueckWStampfussJKubitzaDBeckaMClinical pharmacokinetic and pharmacodynamic profile of rivaroxabanClin Pharmacokinet20145311161:CAS:528:DC%2BC2cXksVaktw%3D%3D10.1007/s40262-013-0100-723999929
– reference: KnepperJHorneDObiAWakefieldTWA systemic update on the state of novel anticoagulants a primer on reversal and bridgingJ Vasc Surg: Venous and Lym Dis20131418426
– reference: Janssen Pharmaceuticals, Inc. XARELTO® (rivaroxaban) package insert. Titusville, NJ: Bayer Healthcare AG; August 2014.
– reference: PollackCVManaging bleeding in anticoagulated patients in the emergency care settingJ Emerg Med20134546747710.1016/j.jemermed.2013.03.01623786779
– reference: KaatzSKouidesPAGarciaDAGuidance on the emergent reversal of oral thrombin and factor 317 Xa inhibitorsAm J Hematol201289S414S145
– reference: ErikssonBIBorrisLCFriedmanRJHaasSHuismanMVKakkarAKBandelTJBeckmannHMuehlhoferEMisselwitzFGeertsWRECORD1 Study GroupRivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplastyN Engl J Med2008358276527751:CAS:528:DC%2BD1cXnvFahtbo%3D10.1056/NEJMoa080037418579811
– reference: ThigenJLLimdiNAReversal of oral anticoagulationPharmacotherapy2013331199121310.1002/phar.1270
– reference: FawoleADawHACrowtherMAPractical management of bleeding due to the anticoagulants dabigatran, rivaroxaban, and apixabanCleve Clin J Med21038044345110.3949/ccjm.80a.13025
– reference: GonzvaJPatricelliRLignacDSpontaneous splenic rupture in a patient treated with rivaroxabanAm J Emerg Med201432950.e310.1016/j.ajem.2014.01.04924612597
– reference: Lauw M, Coppens M, Eikelboom J. Recent advances in antidotes for direct oral anticoagulants: their arrival is imminent. Can J Cardiol 2014. Accepted manuscript pending publication.
– reference: PerzbornEHeitmeierSLauxVBuchmüllerAReversal of rivaroxaban-induced anticoagulation with prothrombin complex concentrate, activated prothrombin complex concentrate and recombinant activated factor VII in vitroThromb Res201413367168110.1016/j.thromres.2014.01.017
– reference: AgenoWGallusASWittkowskyAOral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice GuidelinesChest20122Supple445e885
– reference: RileyTGauthier-LewisMSanchezCRole of agents for reversing the effects of target-specific oral anticoagulantsAm J Health-Syst Pharm2017742546110.2146/ajhp15081027895055This article looked at the various different mechanisms for reversing oral anticoagulants. It also reviewed the latest information on the new reversal agents that are still currently in early trials, but may show some promising effects for reversing oral anticoagulants, especially factor Xa inhibitors.
– reference: MangramAOguntoduODzanduJIs there a difference in efficacy, safety and cost-effectiveness between 3-factor and 4-factor prothrombin complex concentrates among trauma patients on oral anticoagulants?J Crit Care2016332522561:CAS:528:DC%2BC28Xks1yksbg%3D10.1016/j.jcrc.2016.02.01827021851
– reference: LeviMMooreKCastillejosCComparison of three-factor and four-factor prothrombin complex concentrates regarding reversal of the anticoagulant effects of rivaroxaban in healthy volunteersJ Thromb Heamost201412142814361:CAS:528:DC%2BC2cXhsFCjurzP10.1111/jth.12599This study was unable to completely reverse the PT as described in the Eerenberg study. In addition, 4-factor PCC did not produce as robust of a reversal of ETP that 3-factor PCC did. Both 3-factor and 4-factor PCC did not have an effect on activated partial thromboplastin time (APTT). In summary, this study presents evidence for a more muted response to PCC as compared to the Eerenberg study.
– reference: EerenbergESKamphuisenPWSijpkensMKReversal of rivaroxaban and dabigatran by 337 prothrombin complex concentrate. A randomized, placebo-controlled, crossover study in healthy 338 subjectsCirculation2011124157315791:CAS:528:DC%2BC3MXht1GjsLfO10.1161/CIRCULATIONAHA.111.02901721900088This study reports a complete reversal of elevated prothrombin time (PT) and normalization of endogenous thrombin potential (ETP) following administration of 4-factor PCC in humans given rivaroxaban. In summary, this study provides evidence for successful reversal of rivaroxaban with 4-factor PCC via markers of PT and ETP.
– reference: DinkelaarJMolenaarPJNinivaggiMde LaatBBrinkmanHJMLeyteAIn vitro assessment using thrombin generation of the applicability of prothrombin complex concentrate as an antidote for rivaroxabanJ Thromb Haemost 341201311111111181:CAS:528:DC%2BC3sXht12jurbI10.1111/jth.12236
– reference: AkwaaFSpyropoulosACTreatment of bleeding complications when using oral anticoagulants for 332 prevention of strokesCurr Treat Options Cardiovasc Med20131528829810.1007/s11936-013-0238-523494907
– reference: BallaSKoerberSFlakerGManagement of bleeding in patients receiving non-vitamin K antagonistsPostgrad Med J201793109822122510.1136/postgradmedj-2016-13448627986971
– reference: AgnelliGBullerHRCohenACurtoMGallusASJohnsonMMasiukiewiczUPakRThompsonJRaskobGEWeitzJIAMPLIFY InvestigatorsOral apixaban for the treatment of acute venous thromboembolismN Engl J Med20133697998081:CAS:528:DC%2BC3sXhtlyis7fN10.1056/NEJMoa130250723808982
– reference: EINSTEIN InvestigatorsOral rivaroxaban for sympotomatic venous thromboembolismN Engl J Med20103632499251010.1056/NEJMoa1007903
– reference: Hokusai-VTE InvestigatorsEdoxaban versus warfarin for the treatment of symptomatic venous thromboembolismN Engl J Med20133691406141510.1056/NEJMoa1306638
– reference: GrangerCBAlexanderJHMcMurrayJLopesRDHylekEMHannaMal-KhalidiHRAnsellJAtarDAvezumABahitMCDiazREastonJDEzekowitzJAFlakerGGarciaDGeraldesMGershBJGolitsynSGotoSHermosilloAGHohnloserSHHorowitzJMohanPJanskyPLewisBSLopez-SendonJLPaisPParkhomenkoAVerheugtFWZhuJWallentinLARISTOTLE Committees and InvestigatorsApixaban versus warfarin in patients with atrial fibrillationN Engl J Med20113659819921:CAS:528:DC%2BC3MXhtF2ms7rN10.1056/NEJMoa110703921870978
– reference: SchulmanSKakkarAKGoldhaberSZSchellongSErikssonHMismettiPChristiansenAVFriedmanJle MaulfFPeterNKearonCfor the RE-COVER II Trial Investigators*Treatment of acute venous thromboembolism with dabigatranCirculation20141297647721:CAS:528:DC%2BC2cXjtlSnsr0%3D10.1161/CIRCULATIONAHA.113.00445024344086
– reference: PernodGAlbaladejoPGodierASamamaCMSusenSGruelYBlaisNFontanaPCohenALlauJVRosencherNSchvedJFde MaistreESamamaMMMismettiPSiéPWorking Group on Perioperative HaemostasisManagement of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor Xa 320 inhibitors: proposals of the Working Group on Perioperative Haemostasis (GIHP) – March 2013Arch Cardiovasc Dis201310638239310.1016/j.acvd.2013.04.00923810130
– reference: The EINSTEIN InvestigatorsOral rivaroxaban for symptomatic venous thromboembolismN Engl J Med20103632499251010.1056/NEJMoa1007903
– reference: ConnollySMillingTEikelboomJANNEXA-4 investigators. Adenanet alfa for acute major bleeding associated with the factor XA inhibitorsN Engl Med2016375113111411:CAS:528:DC%2BC28XhvF2ksrnM10.1056/NEJMoa1607887
– reference: KalusJSPharmacologic interventions for reversing the effects of oral anticoagulantsAm J Health-Syst Pharm201370S12S211:CAS:528:DC%2BC3sXptVWqtrY%3D10.2146/ajhp13004123640528
– reference: Purruckeer JC, Capper D, Behrens L, Veltkamp R. Secondary hematoma expansion in intracerebral hemorrhage during rivaroxaban therapy. Am J Emerg Med 2014;947e3947.e5.
– reference: PatelMRMahaffeyKWGargJRivaroxaban versus warfarin in nonvalvular atrial fibrillationN 302 Engl J Med20113658838911:CAS:528:DC%2BC3MXhtFKhsLnI10.1056/NEJMoa1009638
– reference: GrandhiRNewmanCZhangXAdministration of 4-factor prothrombin complex concentrate as in antidote for intracranial bleeding in patients taking direct factor Xa inhibitorsWorld Neurosurg20158461956196110.1016/j.wneu.2015.08.04226341438
– reference: ConnollySJEzekowitzMDYusufSEikelboomJOldgrenJParekhAPogueJReillyPAThemelesEVarroneJWangSAlingsMXavierDZhuJDiazRLewisBSDariusHDienerHCJoynerCDWallentinLRE-LY Steering Committee and InvestigatorsDabigatran versus warfarin in patients with atrial fibrillationN Engl J Med2009361113911511:CAS:528:DC%2BD1MXhtFOjsLnN10.1056/NEJMoa090556119717844
– reference: SiegalDMCrowtherMAAcute management of bleeding in patients on novel oral anticoagulantsEur 313 Heart J2013344895001:CAS:528:DC%2BC3sXivFaqtLk%3D10.1093/eurheartj/ehs408
– reference: SteinerTBohmMDichgansMRecommendations for the emergency management of complications associated with the new direct oral anticoagulants (DOACs), apixaban, dabigatran, and rivaroxabanClin Res Cardiol20131023994121:CAS:528:DC%2BC3sXnvFSqt7s%3D10.1007/s00392-013-0560-723669868
– reference: PerzbornEGruberATinelHMarzecUMBuetehornUBuchmuellerAHeitmeierSLauxVReversal of rivaroxaban anticoagulation by haemostatic agents in rats and primatesThromb Haemost20131101621721:CAS:528:DC%2BC3sXhtFKls7jL10.1160/TH12-12-090723636219
– reference: CukerASiegalDCrowtherMLaboratory measurement of the anticoagulant activity of the non-vitamin K oral anticoagulantsJ Am Coll Cardiol201464112811391:CAS:528:DC%2BC2cXhsFerurjL10.1016/j.jacc.2014.05.065252126484167772
– reference: MillerMPTrujilloTCNordenholzKEPractical considerations in emergency management of bleeding in the setting of target-specific oral anticoagulantsAm J Emerg Med20143237538210.1016/j.ajem.2013.11.04424512886
– reference: MaoGKingLYoungSKaplanRFactor eight inhibitor bypassing agent (FIEBA) for reversal of target specific oral anticoagulants in life-threatening intracranial bleedingJ EmergMed201752573173710.1016/j.jemermed.2016.11.011
– reference: KörberMLangerEZiemerSMeasurement and reversal of prophylactic and therapeutic peak levels of rivaroxaban: an in vitro studyClin Appl Thromb Hemost20142073574010.1177/107602961349446823832064
– reference: GodierAMiclotALe BonniecBEvaluation of prothrombin complex concentrate and recombinant activated factor VII to reverse rivaroxaban in a rabbit modelAnesthesiology2012116941021:CAS:528:DC%2BC3MXhs1Gls7nN10.1097/ALN.0b013e318238c03622042412
– reference: MarluRHodajEParisAAlbaladejoPCrackowskiJPernodGEffect of non-specific agents on anticoagulant activity of dabigatran and rivaroxabanThromb Haemost20121082172241:CAS:528:DC%2BC38Xht1GitbrN10.1160/TH12-03-017922627883
– reference: The EINSTEIN-PE InvestigatorsOral rivaroxaban for the treatment of symptomatic pulmonary embolismN Engl J Med20123661287129710.1056/NEJMoa1113572
– reference: SiegalDCurnutteJConnollySAndexanet alfa for the reversal of factor Xa inhibitor activityN Engl J Med2015373241324241:CAS:528:DC%2BC28XitFc%3D10.1056/NEJMoa151099126559317
– reference: AnsellJBakhruSLaulichtBUse of PER977 to reverse the anticoagulant effect of edoxabanN Engl J Med20143712141214210.1056/NEJMc141180025371966
– reference: RomualdiEDonadiniMPAgenoWOral rivaroxaban after symptomatic venous thromboembolism: the continued treatment study (EINSTEIN-extension study)Expert Rev Cardiovasc Ther201198418441:CAS:528:DC%2BC3MXps1ygt78%3D10.1586/erc.11.6221809964
– reference: KakkarAKBrennerBDahlOEErikssonBIMouretPMuntzJSoglianAGPapÁFMisselwitzFHaasSExtended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomized controlled trialLancet200837231391:CAS:528:DC%2BD1cXotlWqsrg%3D10.1016/S0140-6736(08)60880-618582928
– reference: LassenMRAgenoWBorrisLCLiebermanJRRosencherNBandelTJMisselwitzFTurpieAGRECORD3 InvestigatorsRivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplastyN Engl J Med2008358277627861:CAS:528:DC%2BD1cXnvFagt70%3D10.1056/NEJMoa07601618579812
– volume: 102
  start-page: 399
  year: 2013
  ident: 157_CR25
  publication-title: Clin Res Cardiol
  doi: 10.1007/s00392-013-0560-7
– volume: 108
  start-page: 217
  year: 2012
  ident: 157_CR34
  publication-title: Thromb Haemost
  doi: 10.1160/TH12-03-0179
– volume: 12
  start-page: 1428
  year: 2014
  ident: 157_CR40
  publication-title: J Thromb Heamost
  doi: 10.1111/jth.12599
– volume: 45
  start-page: 467
  year: 2013
  ident: 157_CR18
  publication-title: J Emerg Med
  doi: 10.1016/j.jemermed.2013.03.016
– volume: 110
  start-page: 162
  year: 2013
  ident: 157_CR38
  publication-title: Thromb Haemost
  doi: 10.1160/TH12-12-0907
– ident: 157_CR41
  doi: 10.1016/j.ajem.2014.01.042
– volume: 34
  start-page: 489
  year: 2013
  ident: 157_CR19
  publication-title: Eur 313 Heart J
  doi: 10.1093/eurheartj/ehs408
– volume: 361
  start-page: 1139
  year: 2009
  ident: 157_CR9
  publication-title: N Engl J Med
  doi: 10.1056/NEJMoa0905561
– volume: 116
  start-page: 94
  year: 2012
  ident: 157_CR39
  publication-title: Anesthesiology
  doi: 10.1097/ALN.0b013e318238c036
– volume: 363
  start-page: 2499
  year: 2010
  ident: 157_CR7
  publication-title: N Engl J Med
  doi: 10.1056/NEJMoa1007903
– volume: 32
  start-page: 375
  year: 2014
  ident: 157_CR20
  publication-title: Am J Emerg Med
  doi: 10.1016/j.ajem.2013.11.044
– volume: 52
  start-page: 731
  issue: 5
  year: 2017
  ident: 157_CR43
  publication-title: J EmergMed
  doi: 10.1016/j.jemermed.2016.11.011
– volume: 358
  start-page: 2765
  year: 2008
  ident: 157_CR2
  publication-title: N Engl J Med
  doi: 10.1056/NEJMoa0800374
– volume: 369
  start-page: 799
  year: 2013
  ident: 157_CR13
  publication-title: N Engl J Med
  doi: 10.1056/NEJMoa1302507
– volume: 2
  start-page: e445
  issue: Suppl
  year: 2012
  ident: 157_CR17
  publication-title: Chest
– volume: 11
  start-page: 1111
  year: 2013
  ident: 157_CR33
  publication-title: J Thromb Haemost 341
  doi: 10.1111/jth.12236
– volume: 133
  start-page: 671681
  year: 2014
  ident: 157_CR35
  publication-title: Thromb Res
  doi: 10.1016/j.thromres.2014.01.017
– volume: 375
  start-page: 1131
  year: 2016
  ident: 157_CR47
  publication-title: N Engl Med
  doi: 10.1056/NEJMoa1607887
– volume: 372
  start-page: 31
  year: 2008
  ident: 157_CR3
  publication-title: Lancet
  doi: 10.1016/S0140-6736(08)60880-6
– volume: 20
  start-page: 735
  year: 2014
  ident: 157_CR36
  publication-title: Clin Appl Thromb Hemost
  doi: 10.1177/1076029613494468
– volume: 33
  start-page: 1199
  year: 2013
  ident: 157_CR26
  publication-title: Pharmacotherapy
  doi: 10.1002/phar.1270
– volume: 93
  start-page: 221
  issue: 1098
  year: 2017
  ident: 157_CR30
  publication-title: Postgrad Med J
  doi: 10.1136/postgradmedj-2016-134486
– volume: 15
  start-page: 288
  year: 2013
  ident: 157_CR27
  publication-title: Curr Treat Options Cardiovasc Med
  doi: 10.1007/s11936-013-0238-5
– volume: 74
  start-page: 54
  issue: 2
  year: 2017
  ident: 157_CR44
  publication-title: Am J Health-Syst Pharm
  doi: 10.2146/ajhp150810
– volume: 80
  start-page: 443
  year: 2103
  ident: 157_CR24
  publication-title: Cleve Clin J Med
  doi: 10.3949/ccjm.80a.13025
– volume: 371
  start-page: 2141
  year: 2014
  ident: 157_CR48
  publication-title: N Engl J Med
  doi: 10.1056/NEJMc1411800
– volume: 33
  start-page: 252
  year: 2016
  ident: 157_CR16
  publication-title: J Crit Care
  doi: 10.1016/j.jcrc.2016.02.018
– ident: 157_CR1
– volume: 64
  start-page: 1128
  year: 2014
  ident: 157_CR31
  publication-title: J Am Coll Cardiol
  doi: 10.1016/j.jacc.2014.05.065
– volume: 365
  start-page: 981
  year: 2011
  ident: 157_CR10
  publication-title: N Engl J Med
  doi: 10.1056/NEJMoa1107039
– volume: 369
  start-page: 1406
  year: 2013
  ident: 157_CR14
  publication-title: N Engl J Med
  doi: 10.1056/NEJMoa1306638
– volume: 89
  start-page: S414
  year: 2012
  ident: 157_CR21
  publication-title: Am J Hematol
– volume: 84
  start-page: 1956
  issue: 6
  year: 2015
  ident: 157_CR29
  publication-title: World Neurosurg
  doi: 10.1016/j.wneu.2015.08.042
– volume: 373
  start-page: 2413
  year: 2015
  ident: 157_CR46
  publication-title: N Engl J Med
  doi: 10.1056/NEJMoa1510991
– volume: 106
  start-page: 382
  year: 2013
  ident: 157_CR22
  publication-title: Arch Cardiovasc Dis
  doi: 10.1016/j.acvd.2013.04.009
– volume: 53
  start-page: 1
  issue: 1
  year: 2014
  ident: 157_CR15
  publication-title: Clin Pharmacokinet
  doi: 10.1007/s40262-013-0100-7
– volume: 365
  start-page: 883
  year: 2011
  ident: 157_CR6
  publication-title: N 302 Engl J Med
  doi: 10.1056/NEJMoa1009638
– volume: 1
  start-page: 418
  year: 2013
  ident: 157_CR28
  publication-title: J Vasc Surg: Venous and Lym Dis
– volume: 9
  start-page: 841
  year: 2011
  ident: 157_CR5
  publication-title: Expert Rev Cardiovasc Ther
  doi: 10.1586/erc.11.62
– volume: 366
  start-page: 1287
  year: 2012
  ident: 157_CR8
  publication-title: N Engl J Med
  doi: 10.1056/NEJMoa1113572
– volume: 129
  start-page: 764
  year: 2014
  ident: 157_CR11
  publication-title: Circulation
  doi: 10.1161/CIRCULATIONAHA.113.004450
– volume: 124
  start-page: 1573
  year: 2011
  ident: 157_CR32
  publication-title: Circulation
  doi: 10.1161/CIRCULATIONAHA.111.029017
– volume: 363
  start-page: 2499
  year: 2010
  ident: 157_CR12
  publication-title: N Engl J Med
  doi: 10.1056/NEJMoa1007903
– volume: 70
  start-page: S12
  year: 2013
  ident: 157_CR23
  publication-title: Am J Health-Syst Pharm
  doi: 10.2146/ajhp130041
– volume: 32
  start-page: 950.e3
  year: 2014
  ident: 157_CR42
  publication-title: Am J Emerg Med
  doi: 10.1016/j.ajem.2014.01.049
– volume: 358
  start-page: 2776
  year: 2008
  ident: 157_CR4
  publication-title: N Engl J Med
  doi: 10.1056/NEJMoa076016
– volume: 44
  start-page: 771
  year: 2013
  ident: 157_CR37
  publication-title: Stroke
  doi: 10.1161/STROKEAHA.112.675231
– ident: 157_CR45
  doi: 10.1016/j.cjca.2014.01.015
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Snippet Purpose of Review Background: Rivaroxaban is a Xa inhibitor and one of the direct acting oral anticoagulants (DOAC) that currently does not have evidence-based...
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SubjectTerms Anticoagulants
Blood pressure
Cardiac arrhythmia
Creatinine
Drug dosages
Emergency medical care
Emergency Medicine
FDA approval
Heart rate
Hemorrhage
Medicine
Medicine & Public Health
Ostomy
Oxygen saturation
Patients
Plasma
Section Editor
Thrombosis
Thrombosis (D Slattery
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Title Rivaroxaban-Associated Intraparenchymal Hemorrhage Managed with 4-Factor Prothrombin Complex Concentrate
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