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<!DOCTYPE html><html lang="en"><head><title data-react-helmet="true">Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban</title> <meta data-react-helmet="true" name="viewport" content="width=device-width, initial-scale=1, maximum-scale=5, viewport-fit=cover"/><meta data-react-helmet="true" property="og:site_name" content="scite.ai"/><meta data-react-helmet="true" property="og:type" content="website"/><meta data-react-helmet="true" property="twitter:card" content="summary_large_image"/><meta data-react-helmet="true" name="twitter:site" content="@scite"/><meta data-react-helmet="true" property="title" content="Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban"/><meta data-react-helmet="true" property="og:title" content="Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban"/><meta data-react-helmet="true" property="twitter:title" content="Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban"/><meta data-react-helmet="true" property="og:image" content="http://image.thum.io/get/ogImage/https://scite.ai/reports/single-dose-ciraparantag-safely-and-completely-m5QADr?bannerClosed=true&onboardingOff=true&paywallOff=true&v=2"/><meta data-react-helmet="true" property="twitter:image" content="http://image.thum.io/get/ogImage/https://scite.ai/reports/single-dose-ciraparantag-safely-and-completely-m5QADr?bannerClosed=true&onboardingOff=true&paywallOff=true&v=2"/><meta data-react-helmet="true" name="description" content="Supporting: 2, Mentioning: 87 - SummaryOf the new direct oral anticoagulants, direct factor Xa inhibitors are limited by the absence of a proven reversal agent. We assessed the safety, tolerability and impact on anticoagulation reversal of ciraparantag (PER977) alone and following a 60 mg dose of the FXa inhibitor edoxaban. Escalating, single IV doses of ciraparantag were administered alone and following a 60 mg oral dose of edoxaban in a double-blind, placebo-controlled fashion to healthy subjects. Serial assessments of the pharmacokinetics and pharmacodynamic effects of ciraparantag were performed. Eighty male subjects completed the study. Following edoxaban (60 mg), a single IV dose of ciraparantag (100 to 300 mg) demonstrated full reversal of anticoagulation within 10 minutes and sustained for 24 hours. Fibrin diameter within clots was restored to normal 30 minutes after a single dose of 100 to 300 mg ciraparantag as determined by scanning electron microscopy and change in fibrin diameter quantified by automated image analysis. Potentially related adverse events were periorbital and facial flushing and cool sensation following IV injection of ciraparantag. Renal excretion of ciraparantag metabolite was the main elimination route. There was no evidence of procoagulant activity following ciraparantag as assessed by D-dimer, prothrombin fragments 1.2, and tissue factor pathway inhibitor levels. In conclusion, ciraparantag in healthy subjects is safe and well tolerated with minor, non-dose limiting adverse events. Baseline haemostasis was restored from the anticoagulated state with doses of 100 to 300 mg ciraparantag within 10–30 minutes of administration and sustained for at least 24 hours.Institution where the work was performed: Duke University Clinical Research Unit, Duke University Medical Center, Durham, NC USA"/><meta data-react-helmet="true" property="og:description" content="Supporting: 2, Mentioning: 87 - SummaryOf the new direct oral anticoagulants, direct factor Xa inhibitors are limited by the absence of a proven reversal agent. We assessed the safety, tolerability and impact on anticoagulation reversal of ciraparantag (PER977) alone and following a 60 mg dose of the FXa inhibitor edoxaban. Escalating, single IV doses of ciraparantag were administered alone and following a 60 mg oral dose of edoxaban in a double-blind, placebo-controlled fashion to healthy subjects. Serial assessments of the pharmacokinetics and pharmacodynamic effects of ciraparantag were performed. Eighty male subjects completed the study. Following edoxaban (60 mg), a single IV dose of ciraparantag (100 to 300 mg) demonstrated full reversal of anticoagulation within 10 minutes and sustained for 24 hours. Fibrin diameter within clots was restored to normal 30 minutes after a single dose of 100 to 300 mg ciraparantag as determined by scanning electron microscopy and change in fibrin diameter quantified by automated image analysis. Potentially related adverse events were periorbital and facial flushing and cool sensation following IV injection of ciraparantag. Renal excretion of ciraparantag metabolite was the main elimination route. There was no evidence of procoagulant activity following ciraparantag as assessed by D-dimer, prothrombin fragments 1.2, and tissue factor pathway inhibitor levels. In conclusion, ciraparantag in healthy subjects is safe and well tolerated with minor, non-dose limiting adverse events. Baseline haemostasis was restored from the anticoagulated state with doses of 100 to 300 mg ciraparantag within 10–30 minutes of administration and sustained for at least 24 hours.Institution where the work was performed: Duke University Clinical Research Unit, Duke University Medical Center, Durham, NC USA"/><meta data-react-helmet="true" property="twitter:description" content="Supporting: 2, Mentioning: 87 - SummaryOf the new direct oral anticoagulants, direct factor Xa inhibitors are limited by the absence of a proven reversal agent. We assessed the safety, tolerability and impact on anticoagulation reversal of ciraparantag (PER977) alone and following a 60 mg dose of the FXa inhibitor edoxaban. Escalating, single IV doses of ciraparantag were administered alone and following a 60 mg oral dose of edoxaban in a double-blind, placebo-controlled fashion to healthy subjects. Serial assessments of the pharmacokinetics and pharmacodynamic effects of ciraparantag were performed. Eighty male subjects completed the study. Following edoxaban (60 mg), a single IV dose of ciraparantag (100 to 300 mg) demonstrated full reversal of anticoagulation within 10 minutes and sustained for 24 hours. Fibrin diameter within clots was restored to normal 30 minutes after a single dose of 100 to 300 mg ciraparantag as determined by scanning electron microscopy and change in fibrin diameter quantified by automated image analysis. Potentially related adverse events were periorbital and facial flushing and cool sensation following IV injection of ciraparantag. Renal excretion of ciraparantag metabolite was the main elimination route. There was no evidence of procoagulant activity following ciraparantag as assessed by D-dimer, prothrombin fragments 1.2, and tissue factor pathway inhibitor levels. In conclusion, ciraparantag in healthy subjects is safe and well tolerated with minor, non-dose limiting adverse events. Baseline haemostasis was restored from the anticoagulated state with doses of 100 to 300 mg ciraparantag within 10–30 minutes of administration and sustained for at least 24 hours.Institution where the work was performed: Duke University Clinical Research Unit, Duke University Medical Center, Durham, NC USA"/><meta data-react-helmet="true" property="og:url" content="https://scite.ai/reports/single-dose-ciraparantag-safely-and-completely-m5QADr"/><meta data-react-helmet="true" name="citation_title" content="Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban"/><meta data-react-helmet="true" name="citation_doi" content="10.1160/th16-03-0224"/><meta data-react-helmet="true" name="citation_author" content="Ansell, Jack"/><meta data-react-helmet="true" name="citation_author" content="Bakhru, Sasha"/><meta data-react-helmet="true" name="citation_author" content="Laulicht, Bryan"/><meta data-react-helmet="true" name="citation_author" content="Steiner, Solomon S."/><meta data-react-helmet="true" name="citation_author" content="Grosso, Michael"/><meta data-react-helmet="true" name="citation_author" content="Brown, Karen"/><meta data-react-helmet="true" name="citation_author" content="Dishy, Victor"/><meta data-react-helmet="true" name="citation_author" content="Lanz, Hans"/><meta data-react-helmet="true" name="citation_author" content="Mercuri, Michele"/><meta data-react-helmet="true" name="citation_author" content="Noveck, Robert J."/><meta data-react-helmet="true" name="citation_author" content="Costin, James"/><meta data-react-helmet="true" name="citation_year" content="2017"/><meta data-react-helmet="true" name="citation_journal_title" content="Thrombosis and Haemostasis"/><meta data-react-helmet="true" name="citation_volume" content="117"/><meta data-react-helmet="true" name="citation_issue" content="02"/><meta data-react-helmet="true" name="citation_abstract" content="SummaryOf the new direct oral anticoagulants, direct factor Xa inhibitors are limited by the absence of a proven reversal agent. We assessed the safety, tolerability and impact on anticoagulation reversal of ciraparantag (PER977) alone and following a 60 mg dose of the FXa inhibitor edoxaban. Escalating, single IV doses of ciraparantag were administered alone and following a 60 mg oral dose of edoxaban in a double-blind, placebo-controlled fashion to healthy subjects. Serial assessments of the pharmacokinetics and pharmacodynamic effects of ciraparantag were performed. Eighty male subjects completed the study. Following edoxaban (60 mg), a single IV dose of ciraparantag (100 to 300 mg) demonstrated full reversal of anticoagulation within 10 minutes and sustained for 24 hours. Fibrin diameter within clots was restored to normal 30 minutes after a single dose of 100 to 300 mg ciraparantag as determined by scanning electron microscopy and change in fibrin diameter quantified by automated image analysis. Potentially related adverse events were periorbital and facial flushing and cool sensation following IV injection of ciraparantag. Renal excretion of ciraparantag metabolite was the main elimination route. There was no evidence of procoagulant activity following ciraparantag as assessed by D-dimer, prothrombin fragments 1.2, and tissue factor pathway inhibitor levels. In conclusion, ciraparantag in healthy subjects is safe and well tolerated with minor, non-dose limiting adverse events. Baseline haemostasis was restored from the anticoagulated state with doses of 100 to 300 mg ciraparantag within 10–30 minutes of administration and sustained for at least 24 hours.Institution where the work was performed: Duke University Clinical Research Unit, Duke University Medical Center, Durham, NC USA"/><meta data-react-helmet="true" name="citation_public_url" content="https://doi.org/10.1160/th16-03-0224"/> <link data-react-helmet="true" rel="preconnect" href="https://cdn.scite.ai" crossorigin="true"/><link data-react-helmet="true" rel="preconnect" href="https://fonts.googleapis.com"/><link data-react-helmet="true" rel="preconnect" href="https://fonts.gstatic.com" crossorigin="true"/><link data-react-helmet="true" rel="shortcut icon" href="https://cdn.scite.ai/assets/images/favicon.ico"/><link data-react-helmet="true" rel="stylesheet preload prefetch" as="style" href="https://cdn.scite.ai/assets/css/line-awesome-font-awesome.min.css?v=2"/><link data-react-helmet="true" rel="preload" as="style" href="https://fonts.googleapis.com/css2?family=IBM+Plex+Sans:wght@200;300;400;500;600&display=swap"/><link data-react-helmet="true" rel="stylesheet" as="style" href="https://fonts.googleapis.com/css2?family=IBM+Plex+Sans:wght@200;300;400;500;600&display=swap" media="print" onload="this.media='all'"/><link data-react-helmet="true" rel="canonical" href="https://scite.ai/reports/single-dose-ciraparantag-safely-and-completely-m5QADr"/> <script data-react-helmet="true" src="https://www.recaptcha.net/recaptcha/api.js?render=6LcnMGsqAAAAAJLHdGuust5QwzLk-asKPW5MWbAx"></script><script data-react-helmet="true" type="application/ld+json">{"@context":"http://schema.org","@graph":[{"@id":"#issue","@type":"PublicationIssue","issueNumber":"02","datePublished":2017,"isPartOf":{"@id":"#periodical","@type":["PublicationVolume","Periodical"],"name":"Thrombosis and Haemostasis","issn":["0340-6245","2567-689X"],"volumeNumber":"117","publisher":"Georg Thieme Verlag KG"}},{"@type":"ScholarlyArticle","isPartOf":"#issue","description":"SummaryOf the new direct oral anticoagulants, direct factor Xa inhibitors are limited by the absence of a proven reversal agent. We assessed the safety, tolerability and impact on anticoagulation reversal of ciraparantag (PER977) alone and following a 60 mg dose of the FXa inhibitor edoxaban. Escalating, single IV doses of ciraparantag were administered alone and following a 60 mg oral dose of edoxaban in a double-blind, placebo-controlled fashion to healthy subjects. Serial assessments of the pharmacokinetics and pharmacodynamic effects of ciraparantag were performed. Eighty male subjects completed the study. Following edoxaban (60 mg), a single IV dose of ciraparantag (100 to 300 mg) demonstrated full reversal of anticoagulation within 10 minutes and sustained for 24 hours. Fibrin diameter within clots was restored to normal 30 minutes after a single dose of 100 to 300 mg ciraparantag as determined by scanning electron microscopy and change in fibrin diameter quantified by automated image analysis. Potentially related adverse events were periorbital and facial flushing and cool sensation following IV injection of ciraparantag. Renal excretion of ciraparantag metabolite was the main elimination route. There was no evidence of procoagulant activity following ciraparantag as assessed by D-dimer, prothrombin fragments 1.2, and tissue factor pathway inhibitor levels. In conclusion, ciraparantag in healthy subjects is safe and well tolerated with minor, non-dose limiting adverse events. Baseline haemostasis was restored from the anticoagulated state with doses of 100 to 300 mg ciraparantag within 10–30 minutes of administration and sustained for at least 24 hours.Institution where the work was performed: Duke University Clinical Research Unit, Duke University Medical Center, Durham, NC USA","abstract":"SummaryOf the new direct oral anticoagulants, direct factor Xa inhibitors are limited by the absence of a proven reversal agent. We assessed the safety, tolerability and impact on anticoagulation reversal of ciraparantag (PER977) alone and following a 60 mg dose of the FXa inhibitor edoxaban. Escalating, single IV doses of ciraparantag were administered alone and following a 60 mg oral dose of edoxaban in a double-blind, placebo-controlled fashion to healthy subjects. Serial assessments of the pharmacokinetics and pharmacodynamic effects of ciraparantag were performed. Eighty male subjects completed the study. Following edoxaban (60 mg), a single IV dose of ciraparantag (100 to 300 mg) demonstrated full reversal of anticoagulation within 10 minutes and sustained for 24 hours. Fibrin diameter within clots was restored to normal 30 minutes after a single dose of 100 to 300 mg ciraparantag as determined by scanning electron microscopy and change in fibrin diameter quantified by automated image analysis. Potentially related adverse events were periorbital and facial flushing and cool sensation following IV injection of ciraparantag. Renal excretion of ciraparantag metabolite was the main elimination route. There was no evidence of procoagulant activity following ciraparantag as assessed by D-dimer, prothrombin fragments 1.2, and tissue factor pathway inhibitor levels. In conclusion, ciraparantag in healthy subjects is safe and well tolerated with minor, non-dose limiting adverse events. Baseline haemostasis was restored from the anticoagulated state with doses of 100 to 300 mg ciraparantag within 10–30 minutes of administration and sustained for at least 24 hours.Institution where the work was performed: Duke University Clinical Research Unit, Duke University Medical Center, Durham, NC USA","sameAs":"https://doi.org/10.1160/th16-03-0224","pagination":"238-245","name":"Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban","headline":"Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban","author":["Jack Ansell","Sasha Bakhru","Bryan Laulicht","Solomon S. Steiner","Michael Grosso","Karen Brown","Victor Dishy","Hans Lanz","Michele Mercuri","Robert J. Noveck","James Costin"],"publisher":{"@type":"Organization","name":"Georg Thieme Verlag KG"},"datePublished":2017}]}</script> <link data-chunk="main" rel="stylesheet" href="https://cdn.scite.ai/assets/dist/main.2a4a881c9257077826c8.css"> <link data-chunk="Report" rel="stylesheet" href="https://cdn.scite.ai/assets/dist/6901.00ffb5a62514ad11206f.css"> <link data-chunk="Report" rel="stylesheet" href="https://cdn.scite.ai/assets/dist/6392.ee3f7fe674ceac954f77.css"> </head> <body><div id="scite-app"><div class="ReportApp__layout___ljMuO"><div><nav class="NavBar__navBarContainer___skQfv"><div class="NavBar__navBar___ELwVq NavBar__notStatic___bzily" style="transform:translate3d(0,0%,0)"><div class="NavBar__navContents___X2u7r"><a class="NavBar__logo___aYKoi" href="/"><img alt="scite logo" width="115px" height="38px" class="NavBar__logoDesktop___Cwo_2" style="filter:contrast(2.15)" src="https://cdn.scite.ai/assets/images/logo-blue.svg"/><img alt="scite logo" width="64px" height="38px" 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aria-label="https://www.linkedin.com/company/sciteai/"><i class="icon icon-linkedin-new"></i></a></div></div><div class="TitlePaper__paperTitle___zucih"><span><h1 class="Header__h1___YjMd5 TitlePaper__paperTitleHeader___p1alj">Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban</h1></span></div><div class="Authors__authors___uWMEz"><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/jack-ansell-ejL4VZ"><span>Jack Ansell</span></a><sup class="Authors__affiliationSup___Vvflj">1</sup><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/sasha-bakhru-3nDvdb"><span>Sasha Bakhru</span></a><sup class="Authors__affiliationSup___Vvflj">2</sup><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/bryan-laulicht-4L9eMY"><span>Bryan Laulicht</span></a><sup class="Authors__affiliationSup___Vvflj">3</sup><span> </span></div><span class="Authors__link___k07oy">et al.</span></div><div class="TitlePaper__abstractWrapper___S7D_F"><span><h2 class="Header__h2___MuBOH TitlePaper__abstract___GrSZl"><strong>Abstract:</strong>   <span>SummaryOf the new direct oral anticoagulants, direct factor Xa inhibitors are limited by the absence of a proven reversal agent. We assessed the safety, tolerability and impact on anticoagulation reversal of ciraparantag (PER977) alone and following a 60 mg dose of the FXa inhibitor edoxaban. Escalating, single IV doses of ciraparantag were administered alone and following a 60 mg oral dose of edoxaban in a double-blind, placebo-controlled fashion to healthy subjects. Serial assessments of the pharmacokinetics…</span><span class="TitlePaper__expandAbstract___O_45M" role="button" tabindex="0">  Show more</span></h2></span></div><a class="TitlePaper__helpMeCta___oNbp1 Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j TitlePaper__helpMeCta___oNbp1" tabindex="0" role="button">Help me understand this report</a></div></div><div class="ReportDropdown__dropdownMenuContainer___G8S6M"><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div><div><div class="ReportPanel__mainLayout___kuDP5"><div class="ReportPanel__filtersLayout___KAxUi"><div class="Filters__filters___FcFPI"><div class="Filters__loadingLayout___i7nI3" style="opacity:0;pointer-events:auto"><div data-testid="circle-spinner" class="CircleSpinner__sciteLoadingRing___nlTrH" style="width:80px;height:80px"><div class="CircleSpinner__ringComponent____iKPi" style="border-color:#0062ff transparent transparent 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d="M4.516 7.548c0.436-0.446 1.043-0.481 1.576 0l3.908 3.747 3.908-3.747c0.533-0.481 1.141-0.446 1.574 0 0.436 0.445 0.408 1.197 0 1.615-0.406 0.418-4.695 4.502-4.695 4.502-0.217 0.223-0.502 0.335-0.787 0.335s-0.57-0.112-0.789-0.335c0 0-4.287-4.084-4.695-4.502s-0.436-1.17 0-1.615z"></path></svg></div></div></div></div><div class="CheckRowCount__sectionRow___vyiE6"><label class="CheckRow__checkRow___Wumpa"><input class="fa fa-lg fa-check Checkbox__checkbox___dGd5x " type="checkbox"/><span class="CheckRow__checkRowLabel___ax_ST">Ciraparantag</span></label><span><span>2</span></span></div><div class="CheckRowCount__sectionRow___vyiE6"><label class="CheckRow__checkRow___Wumpa"><input class="fa fa-lg fa-check Checkbox__checkbox___dGd5x " type="checkbox"/><span class="CheckRow__checkRowLabel___ax_ST">Reversal Of Oral Anti-factor Xa Agents</span></label><span><span>1</span></span></div><div class="CheckRowCount__sectionRow___vyiE6"><label class="CheckRow__checkRow___Wumpa"><input class="fa 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0-1.615z"></path></svg></div></div></div></div></div></div><div class="CitationsHeader__settingsButtonLayout___SCS1l"><button class="SettingsButton__btn___P6KmW Button__btn___k1xtO Button__btn--transparent___XnBIC Button__size--medium___yX63r Button__tiny___hya9X" aria-label="Settings button"><i class="SettingsButton__icon___w15lK fa fa-sliders-h"></i><span>Settings</span></button></div></div><div class="PapersList__citationList___nW0RR"><div style="opacity:1;pointer-events:auto"><div class="PaperCard__paperCard___Tkx_L PaperCard__card___rYfBl"><div><div><div class="Citation__citation___I7BGj Citation__citationGrid___yNzom"><div class="Citation__rightCol___rqdSW"><div class="Citation__snippetLayout___VCTXv"><div class="Snippet__snippetWrapper___pL8c1"><span><span><div>“…<cite data-doi="10.1056/nejmc1411800">164</cite> In healthy volunteers, it was found to completely reverse the anticoagulant effects of both enoxaparin and edoxaban. <cite class="target" data-doi="10.1160/th16-03-0224">165,</cite><cite data-doi="10.1016/j.thromres.2016.07.008">166</cite> However, further clinical studies are needed before both of these compounds will become available.…”</div></span></span></div></div><div class="Citation__citeInfo___v24kU"><span class="Citation__section___YjAW3"><b>Section</b>: Reversal Of Oral Anti-factor Xa Agents</span><span class="Citation__typeInfo___s7iNF"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="Citation__citationType___LuRbr">mentioning</span><div class="Tooltip__reference___hgPSY"><div class="Citation__classificationDetails___xRtK5"><span class="Citation__classificationDetail___vPtBx">confidence: 99%</span></div></div></span></div></div><div class="Citation__actions___STMoF"><div class="Tooltip__reference___hgPSY"><i class="CopyButton__copyButton___I1ybw fa fa-copy" role="button" tabindex="0"></i></div><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div></div><div aria-hidden="true" class="PaperCard__expandingWrapper___JmHu_" style="overflow:hidden;height:0;opacity:0"><div style="width:fit-content"></div></div></div><div class="PaperCard__grid___NMQAD"><div class="PaperCard__abstractWrapper___Yq394"><div class="Paper__paper___CWi0y"><a class="Paper__title___WkJQP Link__link___plGt2 Link__bold___JGJNO Paper__title___WkJQP" tabindex="0" href="/reports/regional-anesthesia-in-the-patient-68lkWgr"><h3 class="Paper__title___WkJQP">Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy</h3></a><div class="Paper__referenceLine___quVTP"><div class="Authors__authors___uWMEz Paper__lineItem___FXrg7"><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/terese-t-horlocker-y85LzM"><span>Horlocker</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/mayo-clinic-4YK6E">1</a></sup></div><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/erik-vandermeuelen-0GZMV9"><span>Vandermeuelen</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/ku-leuven-5YeG">2</a></sup></div><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/sandra-l-kopp-Kvxk1"><span>Kopp</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/mayo-clinic-4YK6E">3</a></sup></div><span> </span></div><span class="Authors__link___k07oy">et al.</span><span> 2018</span></div><span class="Paper__lineItem___FXrg7"><span class="Reference__reference___AIzFu"><span><a class="Link__link___plGt2 Link__underline___K1Y7j" tabindex="0" href="/journals/regional-anesthesia-pain-medicine-YZQJz"><em>Regional Anesthesia and Pain Medicine</em></a></span></span></span></div><div class="Paper__tallyLayout___k19c4"><a class="HorizontalTally__horizontalTally___gMrpx" href="/reports/regional-anesthesia-in-the-patient-68lkWgr"><div class="HorizontalTally__inner___AzKR8"><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--publications___MBaqU icon-publications"></i><span class="HorizontalTally__count___ZuxQA">733</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--supporting___ru3vm icon-supporting"></i><span class="HorizontalTally__count___ZuxQA">1</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="HorizontalTally__count___ZuxQA">106</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--contradicting___BpYwd icon-contradicting"></i><span class="HorizontalTally__count___ZuxQA">0</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--notices___g0cwl icon-pen"></i><span class="HorizontalTally__count___ZuxQA">2</span></div></div></div></a></div><div class="Paper__linksLayout___Ql9Qd"><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" href="https://doi.org/10.1097/aap.0000000000000763" tabindex="0" role="link" target="_blank" rel="noopener noreferrer nofollow">View full text</a><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" tabindex="0" role="button">Add to dashboard</a><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" tabindex="0" role="button">Cite</a></div></div><div aria-hidden="true" style="overflow:hidden;height:0;opacity:0"><div style="width:auto"><p class="Abstract__abstract___V8wNr Abstract__noAbstract___b7A9r PaperCard__abstract___lR5RS Paragraph__body____m5FY">No abstract</p></div></div></div><div class="PaperCard__menu___wXkM0"><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div></div><div class="PapersList__paywalledCites___XIuJQ"><div class="PapersList__paperCardsLayout___dtzN9"><div class="PaperCard__paperCard___Tkx_L PaperCard__card___rYfBl"><div><div><div class="Citation__citation___I7BGj Citation__citationGrid___yNzom"><div class="Citation__rightCol___rqdSW"><div class="Citation__snippetLayout___VCTXv"><div class="Snippet__snippetWrapper___pL8c1"><span><span><div>“…<cite data-doi="10.1056/nejmc1411800">164</cite> In healthy volunteers, it was found to completely reverse the anticoagulant effects of both enoxaparin and edoxaban. <cite class="target" data-doi="10.1160/th16-03-0224">165,</cite><cite data-doi="10.1016/j.thromres.2016.07.008">166</cite> However, further clinical studies are needed before both of these compounds will become available.…”</div></span></span></div></div><div class="Citation__citeInfo___v24kU"><span class="Citation__section___YjAW3"><b>Section</b>: Reversal Of Oral Anti-factor Xa Agents</span><span class="Citation__typeInfo___s7iNF"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="Citation__citationType___LuRbr">mentioning</span><div class="Tooltip__reference___hgPSY"><div class="Citation__classificationDetails___xRtK5"><span class="Citation__classificationDetail___vPtBx">confidence: 99%</span></div></div></span></div></div><div class="Citation__actions___STMoF"><div class="Tooltip__reference___hgPSY"><i class="CopyButton__copyButton___I1ybw fa fa-copy" role="button" tabindex="0"></i></div><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div></div><div aria-hidden="true" class="PaperCard__expandingWrapper___JmHu_" style="overflow:hidden;height:0;opacity:0"><div style="width:fit-content"></div></div></div><div class="PaperCard__grid___NMQAD"><div class="PaperCard__abstractWrapper___Yq394"><div class="Paper__paper___CWi0y"><a class="Paper__title___WkJQP Link__link___plGt2 Link__bold___JGJNO Paper__title___WkJQP" tabindex="0" href="/reports/regional-anesthesia-in-the-patient-68lkWgr"><h3 class="Paper__title___WkJQP">Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy</h3></a><div class="Paper__referenceLine___quVTP"><div class="Authors__authors___uWMEz Paper__lineItem___FXrg7"><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/terese-t-horlocker-y85LzM"><span>Horlocker</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/mayo-clinic-4YK6E">1</a></sup></div><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/erik-vandermeuelen-0GZMV9"><span>Vandermeuelen</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/ku-leuven-5YeG">2</a></sup></div><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/sandra-l-kopp-Kvxk1"><span>Kopp</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/mayo-clinic-4YK6E">3</a></sup></div><span> </span></div><span class="Authors__link___k07oy">et al.</span><span> 2018</span></div><span class="Paper__lineItem___FXrg7"><span class="Reference__reference___AIzFu"><span><a class="Link__link___plGt2 Link__underline___K1Y7j" tabindex="0" href="/journals/regional-anesthesia-pain-medicine-YZQJz"><em>Regional Anesthesia and Pain Medicine</em></a></span></span></span></div><div class="Paper__tallyLayout___k19c4"><a class="HorizontalTally__horizontalTally___gMrpx" href="/reports/regional-anesthesia-in-the-patient-68lkWgr"><div class="HorizontalTally__inner___AzKR8"><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--publications___MBaqU icon-publications"></i><span class="HorizontalTally__count___ZuxQA">733</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--supporting___ru3vm icon-supporting"></i><span class="HorizontalTally__count___ZuxQA">1</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="HorizontalTally__count___ZuxQA">106</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--contradicting___BpYwd icon-contradicting"></i><span class="HorizontalTally__count___ZuxQA">0</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--notices___g0cwl icon-pen"></i><span class="HorizontalTally__count___ZuxQA">2</span></div></div></div></a></div><div class="Paper__linksLayout___Ql9Qd"><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" href="https://doi.org/10.1097/aap.0000000000000763" tabindex="0" role="link" target="_blank" rel="noopener noreferrer nofollow">View full text</a><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" tabindex="0" role="button">Add to dashboard</a><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" tabindex="0" role="button">Cite</a></div></div><div aria-hidden="true" style="overflow:hidden;height:0;opacity:0"><div style="width:auto"><p class="Abstract__abstract___V8wNr Abstract__noAbstract___b7A9r PaperCard__abstract___lR5RS Paragraph__body____m5FY">No abstract</p></div></div></div><div class="PaperCard__menu___wXkM0"><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div></div><div class="PaperCard__paperCard___Tkx_L PaperCard__card___rYfBl"><div><div><div class="Citation__citation___I7BGj Citation__citationGrid___yNzom"><div class="Citation__rightCol___rqdSW"><div class="Citation__snippetLayout___VCTXv"><div class="Snippet__snippetWrapper___pL8c1"><span><span><div>“…Scanning electron micrographs also demonstrated a dose‐dependent increase in fibrin structure formation following ciraparantag administration. There was no evidence of procoagulant effects following administration of ciraparantag as assessed by D‐dimer, prothrombin fragment 1 + 2 and tissue factor pathway inhibitor (TFPI) levels <cite data-doi="10.1056/nejmc1411800 10.1160/th16-03-0224 10.1016/j.thromres.2016.07.008"></cite>. Ciraparantag is currently under further investigation in phase 2 clinical trials (NCT03288454, NCT03172910).…”</div></span></span></div></div><div class="Citation__citeInfo___v24kU"><span class="Citation__section___YjAW3"><b>Section</b>: Investigational Doac Reversal Agents</span><span class="Citation__typeInfo___s7iNF"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="Citation__citationType___LuRbr">mentioning</span><div class="Tooltip__reference___hgPSY"><div class="Citation__classificationDetails___xRtK5"><span class="Citation__classificationDetail___vPtBx">confidence: 99%</span></div></div></span></div></div><div class="Citation__actions___STMoF"><div class="Tooltip__reference___hgPSY"><i class="CopyButton__copyButton___I1ybw fa fa-copy" role="button" tabindex="0"></i></div><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div><div class="Citation__citation___I7BGj Citation__citationGrid___yNzom"><div class="Citation__rightCol___rqdSW"><div class="Citation__snippetLayout___VCTXv"><div class="Snippet__snippetWrapper___pL8c1"><span><span><div>“…102 Ciraparantag has been assessed in healthy volunteers following administration of a single 60-mg dose of edoxaban. <cite data-doi="10.1056/nejmc1411800">103,</cite><cite class="target" data-doi="10.1160/th16-03-0224">104</cite> In a placebo-controlled, double blind, escalating dose study involving 80 healthy subjects, whole-blood clotting time (WBCT) was used to assess the effects of edoxaban on coagulation and reversal with ciraparantag which reduced the WBCT to within 10% of baseline at 10 minutes post-administration and persisted for 24 hours. Clot structure (as assessed by scanning electron microscopy) was restored to baseline following a single 100 mg IV dose of ciraparantag.…”</div></span></span></div></div><div class="Citation__citeInfo___v24kU"><span class="Citation__section___YjAW3"><b>Section</b>: Ciraparantag</span><span class="Citation__typeInfo___s7iNF"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="Citation__citationType___LuRbr">mentioning</span><div class="Tooltip__reference___hgPSY"><div class="Citation__classificationDetails___xRtK5"><span class="Citation__classificationDetail___vPtBx">confidence: 99%</span></div></div></span></div></div><div class="Citation__actions___STMoF"><div class="Tooltip__reference___hgPSY"><i class="CopyButton__copyButton___I1ybw fa fa-copy" role="button" tabindex="0"></i></div><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div></div><div aria-hidden="true" class="PaperCard__expandingWrapper___JmHu_" style="overflow:hidden;height:0;opacity:0"><div style="width:fit-content"><div class="Citation__citation___I7BGj Citation__citationGrid___yNzom"><div class="Citation__rightCol___rqdSW"><div class="Citation__snippetLayout___VCTXv"><div class="Snippet__snippetWrapper___pL8c1"><span><span><div>“…There was no evidence of procoagulant effects following administration of ciraparantag as assessed by D-dimer, prothrombin fragment 1 + 2 and tissue factor pathway inhibitor (TFPI) levels. <cite data-doi="10.1056/nejmc1411800">[103]</cite><cite class="target" data-doi="10.1160/th16-03-0224">[104]</cite><cite data-doi="10.1016/j.thromres.2016.07.008">[105]</cite> Ciraparantag is currently under further investigation in phase 2 clinical trials (NCT03288454, NCT03172910).…”</div></span></span></div></div><div class="Citation__citeInfo___v24kU"><span class="Citation__section___YjAW3"><b>Section</b>: Ciraparantag</span><span class="Citation__typeInfo___s7iNF"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="Citation__citationType___LuRbr">mentioning</span><div class="Tooltip__reference___hgPSY"><div class="Citation__classificationDetails___xRtK5"><span class="Citation__classificationDetail___vPtBx">confidence: 99%</span></div></div></span></div></div><div class="Citation__actions___STMoF"><div class="Tooltip__reference___hgPSY"><i class="CopyButton__copyButton___I1ybw fa fa-copy" role="button" tabindex="0"></i></div><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div></div></div></div><span class="PaperCard__expandCard___m8Yf4" role="button" tabindex="0"><div class="OpenerIcon__folder___jiKx6 false undefined"><i class="OpenerIcon__angleDown___QHC0i icon icon-down-carret"></i></div>See 1 more Smart Citation</span><div class="PaperCard__grid___NMQAD"><div class="PaperCard__abstractWrapper___Yq394"><div class="Paper__paper___CWi0y"><a class="Paper__title___WkJQP Link__link___plGt2 Link__bold___JGJNO Paper__title___WkJQP" tabindex="0" href="/reports/pharmacological-reversal-of-the-direct-YZk98xG"><h3 class="Paper__title___WkJQP">Pharmacological reversal of the direct oral anticoagulants—A comprehensive review of the literature</h3></a><div class="Paper__referenceLine___quVTP"><div class="Authors__authors___uWMEz Paper__lineItem___FXrg7"><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/joseph-r-shaw-45rOw"><span>Shaw</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/ottawa-hospital-56KV">1</a></sup></div><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/deborah-siegal-1ZmV5V"><span>Siegal</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/mcmaster-university-aY9">2</a></sup></div><span> </span></div><span> 2018</span></div><span class="Paper__lineItem___FXrg7"><span class="Reference__reference___AIzFu"><span><a class="Link__link___plGt2 Link__underline___K1Y7j" tabindex="0" href="/journals/research-and-practice-in-thrombosis-n65MN"><em>Research and Practice in Thrombosis and Haemostasis</em></a></span></span></span></div><div class="Paper__tallyLayout___k19c4"><a class="HorizontalTally__horizontalTally___gMrpx" href="/reports/pharmacological-reversal-of-the-direct-YZk98xG"><div class="HorizontalTally__inner___AzKR8"><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--publications___MBaqU icon-publications"></i><span class="HorizontalTally__count___ZuxQA">40</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--supporting___ru3vm icon-supporting"></i><span class="HorizontalTally__count___ZuxQA">0</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="HorizontalTally__count___ZuxQA">27</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--contradicting___BpYwd icon-contradicting"></i><span class="HorizontalTally__count___ZuxQA">0</span></div></div></div></a></div><div class="Paper__linksLayout___Ql9Qd"><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" href="https://doi.org/10.1002/rth2.12089" tabindex="0" role="link" target="_blank" rel="noopener noreferrer nofollow">View full text</a><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" tabindex="0" role="button">Add to dashboard</a><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" tabindex="0" role="button">Cite</a></div></div><div aria-hidden="true" style="overflow:hidden;height:0;opacity:0"><div style="width:auto"><p class="Abstract__abstract___V8wNr PaperCard__abstract___lR5RS Paragraph__body____m5FY"><span><span>Essentials There remains clinical concern regarding the optimal management of direct oral (DOAC) anticoagulant effect for emergencies such as bleeding or urgent surgery/procedures.Idarucizumab is the preferred agent for urgent reversal of dabigatran for severe bleeding or urgent surgeries/procedures.There are currently no commercially available specific reversal agents for direct Xa inhibitors.Evidence for prothrombin complex concentrate (PCC), activated PCC (aPCC), and recombinant VIIa (rVIIa) is limited primarily to animal bleeding models and studies in human volunteer subjects.PCC, aPCC, or rVIIa may contribute to hemostasis for severe bleeding or urgent surgery/procedures in patients receiving factor Xa inhibitors, or dabigatran if idarucizumab is unavailable but benefits and harms are uncertain. The direct oral anticoagulants (DOACs) are used for stroke prevention in atrial fibrillation (SPAF) and the prevention and treatment of venous thromboembolic disease (VTE). Although DOAC‐associated bleeding events are less frequent as compared to vitamin K antagonists, there is significant concern surrounding physicians’ ability to evaluate and manage DOAC‐associated bleeding when it does occur. Idarucizumab is a specific reversal agent for dabigatran and is the agent of choice for dabigatran reversal in the setting of major bleeding or urgent surgery/procedures. There are no commercially available specific reversal agents for the direct Xa inhibitors. Although they have not been rigorously studied in DOAC‐treated patients requiring urgent anticoagulant reversal, limited evidence from in vitro studies, animal bleeding models, human volunteer studies (in vivo and in vitro) and case series suggest that coagulation factor replacement with prothrombin complex concentrate (PCC) and activated PCC (FEIBA) may contribute to hemostasis. However, the safety and efficacy of these agents and the optimal dosing strategies remain uncertain.</span></span></p></div></div></div><div class="PaperCard__menu___wXkM0"><a class="PaperCard__textButton___ncs_Z" tabindex="0">show abstract</a><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div></div><div class="PaperCard__paperCard___Tkx_L PaperCard__card___rYfBl"><div><div><div class="Citation__citation___I7BGj Citation__citationGrid___yNzom"><div class="Citation__rightCol___rqdSW"><div class="Citation__snippetLayout___VCTXv"><div class="Snippet__snippetWrapper___pL8c1"><span><span><div>“…In addition, andexanet alfa (a truncated form of enzymatically inactive factor Xa which binds factor Xa inhibitors and reverses their anticoagulant effects) was investigated for the reversal of oral factor Xa inhibitors <cite data-doi="10.1160/th14-11-0982">65</cite> . Also under development is ciraparantag <cite class="target" data-doi="10.1160/th16-03-0224">66</cite> , which is at an earlier stage of development as a universal reversal agent for all NOACs.…”</div></span></span></div></div><div class="Citation__citeInfo___v24kU"><span class="Citation__section___YjAW3"><b>Section</b>: Anticoagulation In Patients With Atrial Fibrillation</span><span class="Citation__typeInfo___s7iNF"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="Citation__citationType___LuRbr">mentioning</span><div class="Tooltip__reference___hgPSY"><div class="Citation__classificationDetails___xRtK5"><span class="Citation__classificationDetail___vPtBx">confidence: 99%</span></div></div></span></div></div><div class="Citation__actions___STMoF"><div class="Tooltip__reference___hgPSY"><i class="CopyButton__copyButton___I1ybw fa fa-copy" role="button" tabindex="0"></i></div><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div></div><div aria-hidden="true" class="PaperCard__expandingWrapper___JmHu_" style="overflow:hidden;height:0;opacity:0"><div style="width:fit-content"></div></div></div><div class="PaperCard__grid___NMQAD"><div class="PaperCard__abstractWrapper___Yq394"><div class="Paper__paper___CWi0y"><a class="Paper__title___WkJQP Link__link___plGt2 Link__bold___JGJNO Paper__title___WkJQP" tabindex="0" href="/reports/recent-advances-in-the-understanding-edJ16m"><h3 class="Paper__title___WkJQP">Recent advances in the understanding and management of atrial fibrillation: a focus on stroke prevention</h3></a><div class="Paper__referenceLine___quVTP"><div class="Authors__authors___uWMEz Paper__lineItem___FXrg7"><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/farhan-shahid-y5GZp"><span>Shahid</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/university-of-birmingham-88Q">1</a></sup></div><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/eduard-shantsila-vJMeL4"><span>Shantsila</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/university-of-birmingham-88Q">2</a></sup></div><span>, </span></div><div class="Authors__author___TTnHS"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/authors/gregory-y-h-lip-MVbe3m"><span>Lip</span></a><div class="Tooltip__reference___hgPSY"><sup class="Authors__affiliationSup___Vvflj"><a class="Link__link___plGt2 Link__blueLink___BhE5_" tabindex="0" href="/affiliations/aalborg-university-bn28">3</a></sup></div><span> </span></div><span> 2016</span></div><span class="Paper__lineItem___FXrg7"><span class="Reference__reference___AIzFu"><span><a class="Link__link___plGt2 Link__underline___K1Y7j" tabindex="0" href="/journals/f1000research-zREdb"><em>F1000Res</em></a></span></span></span></div><div class="Paper__tallyLayout___k19c4"><a class="HorizontalTally__horizontalTally___gMrpx" href="/reports/recent-advances-in-the-understanding-edJ16m"><div class="HorizontalTally__inner___AzKR8"><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--publications___MBaqU icon-publications"></i><span class="HorizontalTally__count___ZuxQA">6</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--supporting___ru3vm icon-supporting"></i><span class="HorizontalTally__count___ZuxQA">0</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--mentioning___zHr8j icon-mentioning"></i><span class="HorizontalTally__count___ZuxQA">3</span></div></div><div class="HorizontalTally__column___d6ltY"><div class="Tooltip__reference___hgPSY"><i class="undefined TypeIcon__typeIcon___USGCh icon TypeIcon__typeIcon--contradicting___BpYwd icon-contradicting"></i><span class="HorizontalTally__count___ZuxQA">0</span></div></div></div></a></div><div class="Paper__linksLayout___Ql9Qd"><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" href="https://doi.org/10.12688/f1000research.10176.1" tabindex="0" role="link" target="_blank" rel="noopener noreferrer nofollow">View full text</a><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" tabindex="0" role="button">Add to dashboard</a><a class="Paper__link___YsYPi Link__link___plGt2 Link__blueLink___BhE5_ Link__underline___K1Y7j Paper__link___YsYPi" tabindex="0" role="button">Cite</a></div></div><div aria-hidden="true" style="overflow:hidden;height:0;opacity:0"><div style="width:auto"><p class="Abstract__abstract___V8wNr PaperCard__abstract___lR5RS Paragraph__body____m5FY"><span><span>Atrial fibrillation (AF) is associated with an increased risk of stroke compared with the general population. It is anticipated that by 2030 an estimated 14–17 million patients will be diagnosed with this most prevalent arrhythmia within the European Union. AF-related stroke confers a higher mortality and morbidity risk, and thus early detection and assessment for the initiation of effective stroke prevention with oral anticoagulation (OAC) is crucial. Recent guidelines point to the use of non-vitamin K antagonist OACs (NOACs) where appropriate in stroke prevention of patients with non-valvular AF. At present, there are four NOACS available, with no direct head-to-head comparisons to suggest the superiority of one drug over another. Simple and practical risk assessment tools have evolved over the years to facilitate stroke and bleeding risk assessment in busy clinics and wards to aid decision-making. At present, the CHA 2DS 2VASc (congestive heart failure, hypertension, age 65–74/>75, diabetes mellitus, stroke/transient ischemic attack/thromboembolism, vascular disease, female sex) score is recommended by many international guidelines as a simple and practical method of assessing stroke risk in such patients. Alongside this, use of the HAS BLED (hypertension systolic blood pressure >160 mmHg, abnormal liver/renal function [with creatinine ≥200 μmol/L], stroke, bleeding history or predisposition, labile international normalized ratio [range <60% of the time], elderly [>65], concomitant drugs/alcohol) score aims to identify patients at high risk of bleeding for more regular review and follow-up and draws attention to potentially reversible bleeding risk factors. The aim of this review article is to provide an overview of recent advances in the understanding and management of AF with a focus on stroke prevention.</span></span></p></div></div></div><div class="PaperCard__menu___wXkM0"><a class="PaperCard__textButton___ncs_Z" tabindex="0">show abstract</a><div class=""><i class="fa fa-2x fa-ellipsis-h DropdownMenu__dropdownMenuIcon___LGAcI"></i></div></div></div></div></div></div></div><div class="PapersList__loading___Yxc5F" style="opacity:0;pointer-events:none"><div data-testid="circle-spinner" class="CircleSpinner__sciteLoadingRing___nlTrH" style="width:80px;height:80px"><div class="CircleSpinner__ringComponent____iKPi" style="border-color:#0062ff transparent transparent transparent;width:64px;height:64px;margin:8px;border-width:8px"></div><div class="CircleSpinner__ringComponent____iKPi" style="border-color:#0062ff transparent transparent transparent;width:64px;height:64px;margin:8px;border-width:8px"></div><div class="CircleSpinner__ringComponent____iKPi" style="border-color:#0062ff transparent transparent transparent;width:64px;height:64px;margin:8px;border-width:8px"></div><div class="CircleSpinner__ringComponent____iKPi" style="border-color:#0062ff transparent transparent transparent;width:64px;height:64px;margin:8px;border-width:8px"></div></div></div></div></div></div></div></div></div></div></div><div class="Footer__layout___jrAhC"><div class="Footer__mainLayout___MVOfi"><div class="Footer__aboutContainer___TwE0S"><img width="128px" height="41px" alt="scite logo" src="https://cdn.scite.ai/assets/images/logo.svg"/><p class="Paragraph__body____m5FY">scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.</p><div class="Footer__contact___DGc_M"><h6 class="Header__h6___QzBvp">Contact Info</h6><div><p class="Footer__address___VMUTY Paragraph__body____m5FY">customersupport@researchsolutions.com</p><p class="Footer__address___VMUTY Paragraph__body____m5FY">10624 S. 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of oral anti-factor xa agents","type":"mentioning","typeConfidence":1,"snippet":"\u003Ccite data-doi=\"10.1056\u002Fnejmc1411800\"\u003E164\u003C\u002Fcite\u003E In healthy volunteers, it was found to completely reverse the anticoagulant effects of both enoxaparin and edoxaban. \u003Ccite data-doi=\"10.1160\u002Fth16-03-0224\"\u003E165,\u003C\u002Fcite\u003E\u003Ccite data-doi=\"10.1016\u002Fj.thromres.2016.07.008\"\u003E166\u003C\u002Fcite\u003E However, further clinical studies are needed before both of these compounds will become available.","lang":"en","langConfidence":"0.9700000286102295","refLocation":"b168\u002F1","memberId":239,"selfCites":[],"snippetHidden":false},{"id":1700560846,"source":"10.1002\u002Frth2.12089","target":"10.1160\u002Fth16-03-0224","negative":0.034890170395374294,"positive":0.02247053198516369,"neutral":1,"section":"investigational doac reversal agents","type":"mentioning","typeConfidence":1,"snippet":"Scanning electron micrographs also demonstrated a dose‐dependent increase in fibrin structure formation following ciraparantag administration. There was no evidence of procoagulant effects following administration of ciraparantag as assessed by D‐dimer, prothrombin fragment 1 + 2 and tissue factor pathway inhibitor (TFPI) levels \u003Ccite data-doi=\"10.1056\u002Fnejmc1411800 10.1160\u002Fth16-03-0224 10.1016\u002Fj.thromres.2016.07.008\"\u003E\u003C\u002Fcite\u003E. Ciraparantag is currently under further investigation in phase 2 clinical trials (NCT03288454, NCT03172910).","lang":"en","langConfidence":"0.8899999856948853","refLocation":"rth212089-bib-0104\u002F2","memberId":78,"selfCites":[],"snippetHidden":false},{"id":1753158390,"source":"10.1002\u002Frth2.12089","target":"10.1160\u002Fth16-03-0224","negative":0.013020548969507217,"positive":0.008286386728286743,"neutral":1,"section":"ciraparantag","type":"mentioning","typeConfidence":1,"snippet":"102 Ciraparantag has been assessed in healthy volunteers following administration of a single 60-mg dose of edoxaban. \u003Ccite data-doi=\"10.1056\u002Fnejmc1411800\"\u003E103,\u003C\u002Fcite\u003E\u003Ccite data-doi=\"10.1160\u002Fth16-03-0224\"\u003E104\u003C\u002Fcite\u003E In a placebo-controlled, double blind, escalating dose study involving 80 healthy subjects, whole-blood clotting time (WBCT) was used to assess the effects of edoxaban on coagulation and reversal with ciraparantag which reduced the WBCT to within 10% of baseline at 10 minutes post-administration and persisted for 24 hours. Clot structure (as assessed by scanning electron microscopy) was restored to baseline following a single 100 mg IV dose of ciraparantag.","lang":"en","langConfidence":"0.9300000071525574","refLocation":"b103\u002F1","memberId":78,"selfCites":[],"snippetHidden":false},{"id":1753158393,"source":"10.1002\u002Frth2.12089","target":"10.1160\u002Fth16-03-0224","negative":0.009271304681897163,"positive":0.013438915833830833,"neutral":1,"section":"ciraparantag","type":"mentioning","typeConfidence":1,"snippet":"There was no evidence of procoagulant effects following administration of ciraparantag as assessed by D-dimer, prothrombin fragment 1 + 2 and tissue factor pathway inhibitor (TFPI) levels. \u003Ccite data-doi=\"10.1056\u002Fnejmc1411800\"\u003E[103]\u003C\u002Fcite\u003E\u003Ccite data-doi=\"10.1160\u002Fth16-03-0224\"\u003E[104]\u003C\u002Fcite\u003E\u003Ccite data-doi=\"10.1016\u002Fj.thromres.2016.07.008\"\u003E[105]\u003C\u002Fcite\u003E Ciraparantag is currently under further investigation in phase 2 clinical trials (NCT03288454, NCT03172910).","lang":"en","langConfidence":"0.9100000262260437","refLocation":"b103\u002F2","memberId":78,"selfCites":[],"snippetHidden":false},{"id":1436711068,"source":"10.12688\u002Ff1000research.10176.1","target":"10.1160\u002Fth16-03-0224","negative":0.01182398982346058,"positive":0.011581504717469215,"neutral":1,"section":"anticoagulation in patients with atrial fibrillation","type":"mentioning","typeConfidence":1,"snippet":"In addition, andexanet alfa (a truncated form of enzymatically inactive factor Xa which binds factor Xa inhibitors and reverses their anticoagulant effects) was investigated for the reversal of oral factor Xa inhibitors\n \u003Ccite data-doi=\"10.1160\u002Fth14-11-0982\"\u003E65\u003C\u002Fcite\u003E . Also under development is ciraparantag\n \u003Ccite data-doi=\"10.1160\u002Fth16-03-0224\"\u003E66\u003C\u002Fcite\u003E , which is at an earlier stage of development as a universal reversal agent for all NOACs.","lang":"en","langConfidence":"0.9399999976158142","refLocation":"ref-66\u002F1","memberId":2560,"selfCites":[],"snippetHidden":false},{"source":"10.1001\u002Fjamasurg.2018.0374","target":"10.1160\u002Fth16-03-0224","selfCites":[],"dataSource":"CR"},{"source":"10.1002\u002F2327-6924.12494","target":"10.1160\u002Fth16-03-0224","selfCites":[],"dataSource":"KALA"},{"source":"10.1002\u002F9781118492390.ch7","target":"10.1160\u002Fth16-03-0224","selfCites":[],"dataSource":"CR"},{"source":"10.1002\u002Falr.22210","target":"10.1160\u002Fth16-03-0224","selfCites":[],"dataSource":"CR"},{"source":"10.1002\u002Fcpt.1024","target":"10.1160\u002Fth16-03-0224","selfCites":[],"dataSource":"CR"}],"citationTallies":{"10.1097\u002Faap.0000000000000763":{"total":150,"supporting":1,"contradicting":0,"mentioning":106,"unclassified":43,"doi":"10.1097\u002Faap.0000000000000763","citingPublications":733},"10.12688\u002Ff1000research.10176.1":{"total":3,"supporting":0,"contradicting":0,"mentioning":3,"unclassified":0,"doi":"10.12688\u002Ff1000research.10176.1","citingPublications":6},"10.1002\u002Frth2.12089":{"total":28,"supporting":0,"contradicting":0,"mentioning":27,"unclassified":1,"doi":"10.1002\u002Frth2.12089","citingPublications":40},"10.1001\u002Fjamasurg.2018.0374":{"total":25,"supporting":0,"contradicting":0,"mentioning":24,"unclassified":1,"doi":"10.1001\u002Fjamasurg.2018.0374","citingPublications":30},"10.1002\u002F2327-6924.12494":{"total":7,"supporting":0,"contradicting":0,"mentioning":7,"unclassified":0,"doi":"10.1002\u002F2327-6924.12494","citingPublications":6},"10.1002\u002F9781118492390.ch7":{"total":0,"supporting":0,"contradicting":0,"mentioning":0,"unclassified":0,"doi":"10.1002\u002F9781118492390.ch7","citingPublications":0},"10.1002\u002Falr.22210":{"total":36,"supporting":4,"contradicting":2,"mentioning":28,"unclassified":2,"doi":"10.1002\u002Falr.22210","citingPublications":17},"10.1002\u002Fcpt.1024":{"total":20,"supporting":0,"contradicting":0,"mentioning":20,"unclassified":0,"doi":"10.1002\u002Fcpt.1024","citingPublications":26}},"metadata":{"totalCitationCount":90,"restrictedCitationCount":5,"distinctSourceCount":139},"papers":{"10.1097\u002Faap.0000000000000763":{"id":241827998,"doi":"10.1097\u002Faap.0000000000000763","slug":"regional-anesthesia-in-the-patient-68lkWgr","type":"journal-article","title":"Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy","authors":[{"family":"Horlocker","given":"Terese T.","affiliation":"Mayo Clinic","authorSlug":"terese-t-horlocker-y85LzM","authorName":"Terese T. Horlocker","authorID":"5044620","authorLastKnownAffiliationId":9647,"authorSequenceNumber":1,"affiliationSlug":"mayo-clinic-4YK6E","affiliationID":"240386"},{"family":"Vandermeuelen","given":"Erik","affiliation":"KU Leuven","authorSlug":"erik-vandermeuelen-0GZMV9","authorName":"Erik Vandermeuelen","authorID":"6841212","authorLastKnownAffiliationId":4225,"authorSequenceNumber":2,"affiliationSlug":"ku-leuven-5YeG","affiliationID":"4225"},{"family":"Kopp","given":"Sandra L.","affiliation":"Mayo Clinic","authorSlug":"sandra-l-kopp-Kvxk1","authorName":"Sandra L. Kopp","authorID":"1177735","authorLastKnownAffiliationId":4797,"authorSequenceNumber":3,"affiliationSlug":"mayo-clinic-4YK6E","affiliationID":"240386"},{"family":"Gogarten","given":"W.","affiliation":"Klinikum Bielefeld","authorSlug":"w-gogarten-keL0NM","authorName":"W. Gogarten","authorID":"4807568","authorLastKnownAffiliationId":182663,"authorSequenceNumber":4,"affiliationSlug":"klinikum-bielefeld-Dx2We","affiliationID":"182663"},{"family":"Leffert","given":"Lisa","affiliation":"Massachusetts General Hospital","authorSlug":"lisa-leffert-3nkNRK","authorName":"Lisa Leffert","authorID":"5633500","authorLastKnownAffiliationId":199271,"authorSequenceNumber":5,"affiliationSlug":"massachusetts-general-hospital-LDZRE","affiliationID":"191484"},{"family":"Benzon","given":"Honorio T.","affiliation":"Northwestern University","authorSlug":"honorio-t-benzon-ejZXP6","authorName":"Honorio T. Benzon","authorID":"6048155","authorLastKnownAffiliationId":184755,"authorSequenceNumber":6,"affiliationSlug":"northwestern-university-Y0NE","affiliationID":"17807"}],"keywords":["Regional anesthesia and acute pain: Special article"],"year":2018,"shortJournal":"Regional Anesthesia and Pain Medicine","publisher":"BMJ","issue":"3","volume":"43","page":"263-309","retracted":false,"memberId":239,"issns":["1098-7339"],"editorialNotices":[{"status":"Comment","date":"2018-4","noticeDoi":"10.1097\u002Faap.0000000000000771","doi":"10.1097\u002Faap.0000000000000763"},{"status":"Has erratum","date":"2018-7","noticeDoi":"10.1097\u002Faap.0000000000000807","doi":"10.1097\u002Faap.0000000000000763"}],"journalSlug":"regional-anesthesia-pain-medicine-YZQJz","journal":"Regional Anesthesia and Pain Medicine","preprintLinks":[],"publicationLinks":[],"normalizedTypes":["article"]},"10.12688\u002Ff1000research.10176.1":{"id":111602811,"doi":"10.12688\u002Ff1000research.10176.1","slug":"recent-advances-in-the-understanding-edJ16m","type":"journal-article","title":"Recent advances in the understanding and management of atrial fibrillation: a focus on stroke prevention","abstract":"Atrial fibrillation (AF) is associated with an increased risk of stroke compared with the general population. It is anticipated that by 2030 an estimated 14–17 million patients will be diagnosed with this most prevalent arrhythmia within the European Union. AF-related stroke confers a higher mortality and morbidity risk, and thus early detection and assessment for the initiation of effective stroke prevention with oral anticoagulation (OAC) is crucial. Recent guidelines point to the use of non-vitamin K antagonist OACs (NOACs) where appropriate in stroke prevention of patients with non-valvular AF. At present, there are four NOACS available, with no direct head-to-head comparisons to suggest the superiority of one drug over another. Simple and practical risk assessment tools have evolved over the years to facilitate stroke and bleeding risk assessment in busy clinics and wards to aid decision-making. At present, the CHA\n2DS\n2VASc (congestive heart failure, hypertension, age 65–74\u002F\u003E75, diabetes mellitus, stroke\u002Ftransient ischemic attack\u002Fthromboembolism, vascular disease, female sex) score is recommended by many international guidelines as a simple and practical method of assessing stroke risk in such patients. Alongside this, use of the HAS BLED (hypertension systolic blood pressure \u003E160 mmHg, abnormal liver\u002Frenal function [with creatinine ≥200 μmol\u002FL], stroke, bleeding history or predisposition, labile international normalized ratio [range \u003C60% of the time], elderly [\u003E65], concomitant drugs\u002Falcohol) score aims to identify patients at high risk of bleeding for more regular review and follow-up and draws attention to potentially reversible bleeding risk factors. The aim of this review article is to provide an overview of recent advances in the understanding and management of AF with a focus on stroke prevention.","authors":[{"family":"Shahid","given":"Farhan","affiliation":"University of Birmingham","authorSlug":"farhan-shahid-y5GZp","authorName":"Farhan Shahid","authorID":"1324320","authorLastKnownAffiliationId":181635,"authorSequenceNumber":1,"affiliationSlug":"university-of-birmingham-88Q","affiliationID":"365"},{"family":"Shantsila","given":"Eduard","affiliation":"University of Birmingham","authorSlug":"eduard-shantsila-vJMeL4","authorName":"Eduard Shantsila","authorID":"6062053","authorLastKnownAffiliationId":273109,"authorSequenceNumber":2,"affiliationSlug":"university-of-birmingham-88Q","affiliationID":"365"},{"family":"Lip","given":"Gregory Y. H.","affiliation":"Aalborg University","authorSlug":"gregory-y-h-lip-MVbe3m","authorName":"Gregory Y. H. Lip","authorID":"5732996","authorLastKnownAffiliationId":273109,"authorSequenceNumber":3,"affiliationSlug":"aalborg-university-bn28","affiliationID":"25215"}],"keywords":["Review"],"year":2016,"shortJournal":"F1000Res","publisher":"F1000 Research Ltd","volume":"5","page":"2887","retracted":false,"memberId":2560,"issns":["2046-1402"],"editorialNotices":[],"journalSlug":"f1000research-zREdb","journal":"F1000Research","preprintLinks":[],"publicationLinks":[],"normalizedTypes":["article"]},"10.1002\u002Frth2.12089":{"id":230178407,"doi":"10.1002\u002Frth2.12089","slug":"pharmacological-reversal-of-the-direct-YZk98xG","type":"journal-article","title":"Pharmacological reversal of the direct oral anticoagulants—A comprehensive review of the literature","abstract":"Essentials\nThere remains clinical concern regarding the optimal management of direct oral (DOAC) anticoagulant effect for emergencies such as bleeding or urgent surgery\u002Fprocedures.Idarucizumab is the preferred agent for urgent reversal of dabigatran for severe bleeding or urgent surgeries\u002Fprocedures.There are currently no commercially available specific reversal agents for direct Xa inhibitors.Evidence for prothrombin complex concentrate (PCC), activated PCC (aPCC), and recombinant VIIa (rVIIa) is limited primarily to animal bleeding models and studies in human volunteer subjects.PCC, aPCC, or rVIIa may contribute to hemostasis for severe bleeding or urgent surgery\u002Fprocedures in patients receiving factor Xa inhibitors, or dabigatran if idarucizumab is unavailable but benefits and harms are uncertain.\n\nThe direct oral anticoagulants (DOACs) are used for stroke prevention in atrial fibrillation (SPAF) and the prevention and treatment of venous thromboembolic disease (VTE). Although DOAC‐associated bleeding events are less frequent as compared to vitamin K antagonists, there is significant concern surrounding physicians’ ability to evaluate and manage DOAC‐associated bleeding when it does occur. Idarucizumab is a specific reversal agent for dabigatran and is the agent of choice for dabigatran reversal in the setting of major bleeding or urgent surgery\u002Fprocedures. There are no commercially available specific reversal agents for the direct Xa inhibitors. Although they have not been rigorously studied in DOAC‐treated patients requiring urgent anticoagulant reversal, limited evidence from in vitro studies, animal bleeding models, human volunteer studies (in vivo and in vitro) and case series suggest that coagulation factor replacement with prothrombin complex concentrate (PCC) and activated PCC (FEIBA) may contribute to hemostasis. However, the safety and efficacy of these agents and the optimal dosing strategies remain uncertain.","authors":[{"family":"Shaw","given":"Joseph R.","affiliation":"Ottawa Hospital","authorSlug":"joseph-r-shaw-45rOw","authorName":"Joseph R. Shaw","authorID":"1040142","authorLastKnownAffiliationId":140222,"authorSequenceNumber":1,"affiliationSlug":"ottawa-hospital-56KV","affiliationID":"13769"},{"family":"Siegal","given":"Deborah","affiliation":"McMaster University","authorSlug":"deborah-siegal-1ZmV5V","authorName":"Deborah Siegal","authorID":"5186803","authorLastKnownAffiliationId":13769,"authorSequenceNumber":2,"affiliationSlug":"mcmaster-university-aY9","affiliationID":"239"}],"keywords":["Review Article"],"year":2018,"shortJournal":"Research and Practice in Thrombosis and Haemostasis","publisher":"Elsevier BV","issue":"2","volume":"2","page":"251-265","retracted":false,"memberId":78,"issns":["2475-0379"],"editorialNotices":[],"journalSlug":"research-and-practice-in-thrombosis-n65MN","journal":"Research and Practice in Thrombosis and Haemostasis","preprintLinks":[],"publicationLinks":[],"normalizedTypes":["article"]},"10.1001\u002Fjamasurg.2018.0374":{"id":222625419,"doi":"10.1001\u002Fjamasurg.2018.0374","slug":"what-surgeons-should-know-about-D1WKllw","type":"journal-article","title":"What Surgeons Should Know About Non–Vitamin K Oral Anticoagulants","abstract":"The anticoagulant effect of NOAC agents is predictable but not readily measurable in routine clinical practice. A number of uncertainties remain surrounding the use of these agents in the perioperative setting. Ongoing prospective studies and randomized clinical trials will provide greater clarity on these management issues in the near future.","authors":[{"family":"Ha","given":"Andrew C.T.","affiliation":"University of Toronto","authorSlug":"andrew-c-t-ha-RVPRGW","authorName":"Andrew C.T. Ha","authorID":"6639370","authorLastKnownAffiliationId":10775,"authorSequenceNumber":2,"affiliationSlug":"university-of-toronto-xWjA","affiliationID":"12922"},{"family":"Rutka","given":"James T.","affiliation":"University of Toronto","authorSlug":"james-t-rutka-K6Gkrl","authorName":"James T. Rutka","authorID":"5735579","authorLastKnownAffiliationId":24405,"authorSequenceNumber":3,"affiliationSlug":"university-of-toronto-xWjA","affiliationID":"12922"},{"family":"Verma","given":"Subodh","affiliation":"University of Toronto","authorSlug":"subodh-verma-0Gv4db","authorName":"Subodh Verma","authorID":"5719712","authorLastKnownAffiliationId":4141,"authorSequenceNumber":4,"affiliationSlug":"university-of-toronto-xWjA","affiliationID":"12922"}],"keywords":[],"year":2018,"shortJournal":"JAMA Surg","publisher":"American Medical Association (AMA)","issue":"6","volume":"153","page":"577","retracted":false,"memberId":10,"issns":["2168-6254"],"editorialNotices":[],"journalSlug":"jama-surgery-Nlyam","journal":"JAMA Surgery","preprintLinks":[],"publicationLinks":[],"normalizedTypes":["article"]},"10.1002\u002F2327-6924.12494":{"id":240780338,"doi":"10.1002\u002F2327-6924.12494","slug":"use-of-direct-oral-anticoagulants-V0GWzQE","type":"journal-article","title":"Use of direct oral anticoagulants for stroke prevention in elderly patients with nonvalvular atrial fibrillation","abstract":"Background and purpose\nFour direct oral anticoagulants (DOACs) are available for the prevention of stroke in nonvalvular atrial fibrillation (NVAF): dabigatran (a direct thrombin inhibitor); and rivaroxaban, apixaban, and edoxaban (factor Xa inhibitors). This article summarizes the safety and efficacy of DOACs for the prevention of stroke in elderly NVAF patients.\nMethods\nPubMed was searched to identify published results of randomized, controlled trials evaluating DOACs for stroke prevention in elderly NVAF patients. Pharmacologic and dose recommendations were obtained from the package inserts.\nConclusions\nDOACs are at least as effective as warfarin for stroke prevention in elderly patients with NVAF. Compared with warfarin, DOACs were associated with reduced risk of intracranial hemorrhage, while some DOACs demonstrated an increase in other bleeding events (e.g., gastrointestinal). The faster onset and offset of action and fewer food and drug interactions of DOACs may be an advantage over warfarin for some patients.\nImplications for practice\nDOACs are an alternative to warfarin with overall equivalent safety and efficacy in elderly patients with NVAF, and may be preferable for some. Stroke risk must always be balanced against potential bleeding risk when determining an optimal anticoagulation treatment plan. Patients’ needs and preferences will also impact this decision.","authors":[{"family":"Oertel","given":"Lynn B.","affiliation":"Massachusetts General Hospital","authorSlug":"lynn-b-oertel-gZaGAz","authorName":"Lynn B. Oertel","authorID":"6830514","authorLastKnownAffiliationId":191484,"authorSequenceNumber":1,"affiliationSlug":"massachusetts-general-hospital-LDZRE","affiliationID":"191484"},{"family":"Fogerty","given":"Annemarie E.","affiliation":"Massachusetts General Hospital","authorSlug":"annemarie-e-fogerty-pn5DLx","authorName":"Annemarie E. Fogerty","authorID":"5064974","authorLastKnownAffiliationId":191484,"authorSequenceNumber":2,"affiliationSlug":"massachusetts-general-hospital-LDZRE","affiliationID":"191484"}],"keywords":["Stroke","atrial fibrillation","anticoagulant agents","direct oral anticoagulants","nurse practitioners","advanced practice nurses Correspondence Lynn Oertel, MS, NP-BC, CACP, Anticoagulant"],"year":2017,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","volume":"29","page":"551-561","retracted":false,"memberId":276,"issns":["2327-6924"],"editorialNotices":[],"journalSlug":"journal-of-the-american-association-2NEQx","journal":"Journal of the American Association of Nurse Practitioners","preprintLinks":[],"publicationLinks":[],"normalizedTypes":["article"]},"10.1002\u002F9781118492390.ch7":{"id":246960938,"doi":"10.1002\u002F9781118492390.ch7","slug":"unusual-causes-of-ischemic-stroke-V0dljGz","type":"other","title":"Unusual causes of ischemic stroke and transient ischemic attack","authors":[{"family":"Caprio","given":"Fan Z.","affiliation":"Northwestern University","authorSlug":"fan-z-caprio-385y22","authorName":"Fan Z. Caprio","authorID":"8713800","authorLastKnownAffiliationId":17807,"authorSequenceNumber":1,"affiliationSlug":"northwestern-university-Y0NE","affiliationID":"17807"},{"family":"Lin","given":"Chen","affiliation":"Northwestern University","authorSlug":"chen-lin-K6Rkj2","authorName":"Chen Lin","authorID":"6927035","authorLastKnownAffiliationId":6865,"authorSequenceNumber":2,"affiliationSlug":"northwestern-university-Y0NE","affiliationID":"17807"}],"year":2019,"publisher":"Wiley","page":"345-398","retracted":false,"memberId":311,"issns":[],"editorialNotices":[],"journal":"Warlow's Stroke","preprintLinks":[],"publicationLinks":[],"normalizedTypes":["other"]},"10.1002\u002Falr.22210":{"id":244789599,"doi":"10.1002\u002Falr.22210","slug":"management-and-outcome-of-epistaxis-ejlNE0p","type":"journal-article","title":"Management and outcome of epistaxis under direct oral anticoagulants: a comparison with warfarin","abstract":"\u003CRRH\u003EEpistaxis under DOAs\u003C\u002FRRH\u003E \u003CBOX\u003E\u003CABS\u003EBackground: Epistaxis is one of the more common reasons for emergency room visits. The main risk factor for epistaxis is anticoagulant therapy. Until recently, the main culprit was oral intake of a vitamin K antagonist, such as warfarin, which has a number of side effects. Even more recently, several direct oral anticoagulants, rivaroxaban and dabigatran, have been approved for use.We investigated the possible differences between treatment of epistaxis with direct oral anticoagulants and vitamin K antagonists.\nMethods:We conducted a retrospective cohort study at a tertiary referral center in Germany. All patients who were admitted within a 1-year period were included. Patient files were used to obtain the information.Results: Overall, 677 patients were included in our study. Of these, 159 had been treated with vitamin K antagonists and 49 with direct oral anticoagulants. There were no significant differences in terms of age (p = 0.592), sex (p = 0.372), vital signs, bloodwork, or location of bleeding (p = 0.372). Management of epistaxis between the groups was also comparable (p = 0.399), with similar hospital admission rates (37.1% vs 24.5%; p = 0.145) and duration of stay (3.5 ± 2.1 days vs 3.8 ± 3.3 days; p = 0.650).","authors":[{"family":"Send","given":"Thorsten","affiliation":"University Hospital Bonn","authorSlug":"thorsten-send-YgKd2x","authorName":"Thorsten Send","authorID":"8116407","authorLastKnownAffiliationId":212651,"authorSequenceNumber":1,"affiliationSlug":"university-hospital-bonn-kbZL","affiliationID":"17524"},{"family":"Bertlich","given":"Mattis","affiliation":"München Klinik","authorSlug":"mattis-bertlich-5YjGrW","authorName":"Mattis Bertlich","authorID":"8777069","authorLastKnownAffiliationId":24291,"authorSequenceNumber":2,"affiliationSlug":"munchen-klinik-1gnPe","affiliationID":"177647"},{"family":"Horlbeck","given":"Fritz","affiliation":"University Hospital Bonn","authorSlug":"fritz-horlbeck-PzZKM0","authorName":"Fritz Horlbeck","authorID":"11193401","authorLastKnownAffiliationId":17524,"authorSequenceNumber":3,"affiliationSlug":"university-hospital-bonn-kbZL","affiliationID":"17524"},{"family":"Schafigh","given":"Darius","affiliation":"University Hospital Bonn","authorSlug":"darius-schafigh-YDzEkE","authorName":"Darius Schafigh","authorID":"14967995","authorLastKnownAffiliationId":163536,"authorSequenceNumber":4,"affiliationSlug":"university-hospital-bonn-kbZL","affiliationID":"17524"},{"family":"Freytag","given":"Saskia","affiliation":"Walter and Eliza Hall Institute of Medical Research","authorSlug":"saskia-freytag-vJ3gmv","authorName":"Saskia Freytag","authorID":"5198097","authorLastKnownAffiliationId":4776,"authorSequenceNumber":5,"affiliationSlug":"walter-and-eliza-hall-institute-2WEm","affiliationID":"4776"},{"family":"Eichhorn","given":"Klaus","affiliation":"University Hospital Bonn","authorSlug":"klaus-eichhorn-zR0vAE","authorName":"Klaus Eichhorn","authorID":"6087506","authorLastKnownAffiliationId":212651,"authorSequenceNumber":6,"affiliationSlug":"university-hospital-bonn-kbZL","affiliationID":"17524"},{"family":"Gräff","given":"Ingo","affiliation":"University Hospital Bonn","authorSlug":"ingo-graff-bO9Kjp","authorName":"Ingo Gräff","authorID":"8336615","authorLastKnownAffiliationId":17524,"authorSequenceNumber":7,"affiliationSlug":"university-hospital-bonn-kbZL","affiliationID":"17524"},{"family":"Bootz","given":"Friedrich","affiliation":"University Hospital Bonn","authorSlug":"friedrich-bootz-V01GNz","authorName":"Friedrich Bootz","authorID":"6258938","authorLastKnownAffiliationId":212651,"authorSequenceNumber":8,"affiliationSlug":"university-hospital-bonn-kbZL","affiliationID":"17524"},{"family":"Jakob","given":"Mark","affiliation":"München Klinik","authorSlug":"mark-jakob-0GkdwL","authorName":"Mark Jakob","authorID":"5656212","authorLastKnownAffiliationId":14015,"authorSequenceNumber":9,"affiliationSlug":"munchen-klinik-1gnPe","affiliationID":"177647"}],"keywords":[],"year":2018,"shortJournal":"Int Forum Allergy Rhinol","publisher":"Wiley","issue":"1","volume":"9","page":"120-124","retracted":false,"memberId":311,"issns":["2042-6976","2042-6984"],"editorialNotices":[],"journalSlug":"international-forum-of-allergy-wmK3M","journal":"International Forum of Allergy &Amp; Rhinology","preprintLinks":[],"publicationLinks":[],"normalizedTypes":["article"]},"10.1002\u002Fcpt.1024":{"id":242509118,"doi":"10.1002\u002Fcpt.1024","slug":"underuse-of-vitamin-k-antagonist-dvYbj1j","type":"journal-article","title":"Underuse of Vitamin K Antagonist and Direct Oral Anticoagulants for Stroke Prevention in Patients With Atrial Fibrillation: A Contemporary Review","abstract":"Atrial fibrillation (AF) is a leading cause of stroke. Oral anticoagulant (OAC) therapy can significantly reduce the risk of stroke in patients with AF, but underuse of OACs for stroke prevention continues to be a serious clinical problem, with significant deleterious impact on outcomes. We review the studies demonstrating OAC underutilization and evaluating strategies for promoting the increased use of OAC therapy for stroke prevention in nonvalvular AF (NVAF) patients, including in special patient populations.","authors":[{"family":"Hsu","given":"Jonathan C.","affiliation":"University of California San Diego Medical Center","authorSlug":"jonathan-c-hsu-G3rlG1","authorName":"Jonathan C. Hsu","authorID":"6003513","authorLastKnownAffiliationId":6762,"authorSequenceNumber":1,"affiliationSlug":"university-of-california-san-diego-YZ6NG","affiliationID":"147507"},{"family":"Freeman","given":"James V.","affiliation":"Yale University","authorSlug":"james-v-freeman-dvmXrb","authorName":"James V. Freeman","authorID":"6390018","authorLastKnownAffiliationId":8068,"authorSequenceNumber":2,"affiliationSlug":"yale-university-kyQE","affiliationID":"8068"}],"keywords":[],"year":2018,"shortJournal":"Clin Pharma and Therapeutics","publisher":"Wiley","issue":"2","volume":"104","page":"301-310","retracted":false,"memberId":311,"issns":["0009-9236","1532-6535"],"editorialNotices":[],"journalSlug":"clinical-pharmacology-therapeutics-mOmrY","journal":"Clinical Pharmacology &Amp; Therapeutics","preprintLinks":[],"publicationLinks":[],"normalizedTypes":["article"]},"10.1160\u002Fth16-03-0224":{"id":106662187,"doi":"10.1160\u002Fth16-03-0224","slug":"single-dose-ciraparantag-safely-and-completely-m5QADr","type":"journal-article","title":"Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban","abstract":"SummaryOf the new direct oral anticoagulants, direct factor Xa inhibitors are limited by the absence of a proven reversal agent. We assessed the safety, tolerability and impact on anticoagulation reversal of ciraparantag (PER977) alone and following a 60 mg dose of the FXa inhibitor edoxaban. Escalating, single IV doses of ciraparantag were administered alone and following a 60 mg oral dose of edoxaban in a double-blind, placebo-controlled fashion to healthy subjects. Serial assessments of the pharmacokinetics and pharmacodynamic effects of ciraparantag were performed. Eighty male subjects completed the study. Following edoxaban (60 mg), a single IV dose of ciraparantag (100 to 300 mg) demonstrated full reversal of anticoagulation within 10 minutes and sustained for 24 hours. Fibrin diameter within clots was restored to normal 30 minutes after a single dose of 100 to 300 mg ciraparantag as determined by scanning electron microscopy and change in fibrin diameter quantified by automated image analysis. Potentially related adverse events were periorbital and facial flushing and cool sensation following IV injection of ciraparantag. Renal excretion of ciraparantag metabolite was the main elimination route. There was no evidence of procoagulant activity following ciraparantag as assessed by D-dimer, prothrombin fragments 1.2, and tissue factor pathway inhibitor levels. In conclusion, ciraparantag in healthy subjects is safe and well tolerated with minor, non-dose limiting adverse events. Baseline haemostasis was restored from the anticoagulated state with doses of 100 to 300 mg ciraparantag within 10–30 minutes of administration and sustained for at least 24 hours.Institution where the work was performed: Duke University Clinical Research Unit, Duke University Medical Center, Durham, NC USA","authors":[{"family":"Ansell","given":"Jack","authorSlug":"jack-ansell-ejL4VZ","authorName":"Jack Ansell","authorID":"4850455","authorLastKnownAffiliationId":23381,"authorSequenceNumber":1},{"family":"Bakhru","given":"Sasha","authorSlug":"sasha-bakhru-3nDvdb","authorName":"Sasha Bakhru","authorID":"6749800","authorLastKnownAffiliationId":162979,"authorSequenceNumber":2},{"family":"Laulicht","given":"Bryan","authorSlug":"bryan-laulicht-4L9eMY","authorName":"Bryan Laulicht","authorID":"7131786","authorLastKnownAffiliationId":256420,"authorSequenceNumber":3},{"family":"Steiner","given":"Solomon S.","authorSlug":"solomon-s-steiner-Owd24","authorName":"Solomon S. 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