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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThis article discusses the treatment of acute bleeding in patients taking old and new anticoagulants.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EThromboembolic Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EToxicology Thrombotic Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECritical Care\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EThromboembolic Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EToxicology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EEmergency Medicine\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EThrombotic Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECritical Care\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EColin G. Kaide, MD, Ohio State University, Columbus, Ohio, USA, discussed the treatment of acute bleeding in patients taking old and new anticoagulants. Warfarin reversal involves 2 phases: immediate reversal and sustained reversal. Options for immediate reversal include fresh-frozen plasma (FFP), prothrombin complex concentrate (PCC), and activated PCC (aPCC) factor VIII inhibitor bypassing activity (FEIBA; \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/15522\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/15522\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/15522\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-3\u0022 class=\u0022first-child\u0022\u003EOptions for Immediate Warfarin Reversal\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-5\u0022\u003EFor sustained reversal of warfarin, vitamin K must be given. Vitamin K promotes generation of the active forms of factors II, VII, IX, and X; it can be administered orally or intravenously [Ansell J et al. \u003Cem\u003EChest\u003C\/em\u003E. 2008].\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EUnfractionated heparin (UFH) can be reversed with protamine, which binds to and inactivates heparin. Protamine is administered at 1 mg\/100 U UFH to a maximum dose of 50 mg. Protamine is not fully effective against low-molecular-weight heparin (LMWH). For enoxaparin reversal, protamine should be administered at 1 mg\/1 mg enoxaparin if LMWH was taken within the previous 8 hours or at 0.5 mg\/1 mg enoxaparin if LMWH was taken within 8 to 12 hours, up to a maximum of 50mg. Dosing should be repeated if the bleeding has not stopped and antifactor Xa levels are elevated 2 to 4 hours after the last protamine dose [Hirsh J et al. \u003Cem\u003EChest\u003C\/em\u003E. 2001].\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EOne study found the anticoagulant effect of the fondaparinux was shown to be reversible in healthy volunteers with the administration of rVIIa dosed at 90 \u03bcg\/kg [Bijsterveld NR et al. \u003Cem\u003ECirculation\u003C\/em\u003E. 2002]. Another study found that rVIIa did not significantly reverse markers of anticoagulation for fondaparinux, whereas markers were likely improved with administration of PCC and completely reversed with aPCC (Feiba) [Desmurs-Clavel H et al. \u003Cem\u003EThromb Res.\u003C\/em\u003E 2009].\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003ESeveral new oral anticoagulants (NOACs) have been developed. Among them are the direct thrombin inhibitors, dabigatran, and the direct-factor Xa inhibitors, rivaroxaban and apixaban. Reversing the action of these agents is a challenge. Hemodialysis can stop the activity of dabigatran but not of rivaroxaban and apixaban (\u003Ca id=\u0022xref-table-wrap-2-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003ETable 2\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022T2\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/15523\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/15523\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/15523\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 2.\u003C\/span\u003E \n            \u003Cp id=\u0022p-9\u0022 class=\u0022first-child\u0022\u003EReversal of Dabigatran, Rivaroxaban, and Apixaban\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-11\u0022\u003ESpecific reversal agents for the NOACs are under development. For dabigatran, a humanized monoclonal antibody fragment is currently being investigated in several animal and in vitro studies. Clinical trials are currently underway studying the recombinant factor Xa derivative, and adexanet alfa, as a specific reversal agent for rivaroxaban [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT02220725\u0026amp;atom=%2Fspmdc%2F14%2F46%2F10.atom\u0022\u003ENCT02220725\u003C\/a\u003E] and apixaban [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT02207725\u0026amp;atom=%2Fspmdc%2F14%2F46%2F10.atom\u0022\u003ENCT02207725\u003C\/a\u003E]. This agent is a factor Xa decoy that targets and sequesters direct and indirect factor Xa inhibitors in the blood. Once bound, the factor Xa inhibitors cannot bind and inhibit native factor Xa, allowing restoration of normal hemostasis.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EPlatelet inhibitors, including salicylates, clopidogrel, and factor IIb\/IIIa inhibitors may be somewhat reversed by transfusion of platelets [Vilahur G et al. \u003Cem\u003EJ Thromb Haemost\u003C\/em\u003E. 2007] and desmopressin [Leithouser B et al. \u003Cem\u003EClin Hemorheol\u003C\/em\u003E. 2008], but there is no definitive proof. If reversal is attempted using platelets, 2 to 3 pools of platelets should be used. \u03b5-Aminocaproic acid is an antifibrinolytic agent used for hemophiliacs that might reverse fibrinolytics, but there are no data supporting this use [Stief T. \u003Cem\u003EClin Appl Thromb Hemost\u003C\/em\u003E. 2008].\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003EDr Kaide concluded that anticoagulant reversal should be attempted in situations where \u201cmaximal harm is already in progress\u201d and the risk of bleeding outweighs the risk of reversal of anticoagulation. New antidotes for the NOACs are under development and will be available in the near future.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/46\/10.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzlyw3\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzlyw3\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}