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of all cases&#41;&#46; However&#44; a priori&#44; bleeding produced by trauma should be regarded as a potentially reversible cause of mortality provided surgical damage control measures are adopted or coagulopathy associated to trauma is avoided&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3&#44;4</span></a> Nevertheless&#44; if the patient is under the effects of some anticoagulant medication&#44; the risk of bleeding increases&#8211;especially if anticoagulation cannot be quickly reverted&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Warfarin is prescribed in about 12&#46;8&#37; of the patients in the United States&#44; mostly in elderly individuals over 65 years of age with chronic atrial fibrillation &#40;AF&#41;&#44; with the purpose of avoiding cardioembolic phenomena&#44; among other problems&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> The development and increasingly widespread use of new oral anticoagulants &#40;NOAs&#41; imply a change in management strategy when patients who use these drugs suffer severe bleeding&#44; independently of its spontaneous or traumatic origin&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#44;7</span></a> At present&#44; the lack of effective means for reverting the effects of NOAs in non-scheduled situations such as after traffic accidents&#44; casual falls or aggressions&#44; where a &#8220;wait and see&#8221; approach is not possible&#44; but constitutes the most critical issue regarding these new anticoagulant drugs&#46; Although the half-life of all NOAs is about 12<span class="elsevierStyleHsp" style=""></span>h&#44; there are a number of situations such as those commented above in which we cannot wait for spontaneous reversion of their effects&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#44;7</span></a> In contrast&#44; when classical anticoagulants are used&#44; such as the vitamin K antagonists&#44; their reversion according to the available time window is well known&#46; Such a reversion or antagonization can be performed using vitamin K&#44; fresh frozen plasma &#40;FFP&#41;&#44; or prothrombin complex concentrate &#40;PCC&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">We obviously cannot forget that anticoagulation&#44; in the context of AF&#44; constitutes the main reversible cause of ischemic stroke&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> Since 1972&#44; when Miller Fisher published a series of recommendations on the management of AF&#44; many studies have attempted to define safer strategies for reducing the risk of embolic events&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">8&#44;9</span></a> Between 1989 and 1993 a total of 6 clinical trials evaluated the usefulness of warfarin versus aspirin or placebo in preventing stroke in patients with arrhythmias of this kind&#46; The data obtained from the global 2900 patients enrolled in these trials showed warfarin use to result in a decrease in cardioembolic phenomena&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a> In this regard&#44; we have established the main advantages and problems associated with the use of vitamin K antagonists&#46; As positive aspects&#44; mention must be made of their reasonable cost&#44; good efficacy&#44; the possibility of knowing their effects upon coagulation&#44; the development of point of care devices that facilitate monitoring of treatment efficacy&#44; dosing optimization through patient genetic studies&#44; and the possibility of practically immediate reversion in the event of bleeding or the need to perform some urgent procedure&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a> As inconveniences&#44; the vitamin K antagonists take time in reaching optimum therapeutic levels &#40;24&#8211;72<span class="elsevierStyleHsp" style=""></span>h&#41;&#44; with a narrow target range &#40;INR 2&#8211;3&#41;&#44; a renal clearance of 90&#37;&#44; unpredictable between- and within-patient responses&#44; the existence of interactions with certain foods and other drugs&#44; and a purported inherent increase in bleeding risk&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a> Because of the above&#44; routine monitoring of coagulation becomes mandatory in this group of patients&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The above inconveniences&#44; together with the high worldwide prevalence of AF associated to population aging &#40;between 3 and 4&#37;&#41;&#44; have probably incentivized the study and development of new drugs that optimize and facilitate adequate prevention of cardioembolic phenomena&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> In this regard&#44; since 2009 a total of four large clinical trials on the use of NOAs have been published&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">12&#8211;15</span></a><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarizes the main advantages and properties of these new drugs&#46; Firstly&#44; NOAs have been shown to offer better prevention of ischemic stroke and embolic events compared with warfarin&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">14&#8211;18</span></a> Secondly&#44; a decrease in severe spontaneous bleeding is observed&#44; especially as regards intracranial hemorrhage&#46; However&#44; it must be noted that dabigatran has been associated to an increased risk of gastrointestinal bleeding&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> Their effects do not require monitoring&#44; thereby improving patient comfort &#8211; though this may be a problem in individuals with treatment adherence problems&#46; It must be emphasized that in the case of important bleeding&#44; excessive dosing&#44; or administration before surgery&#44; we can monitor the effects of these drugs upon coagulation&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a> Nevertheless&#44; no laboratory value has yet been found to reliably determine NOA activity&#44; since some specific parameters may be under- or overestimated &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">In the same way as with the classical anticoagulants&#44; NOAs can interact with other drugs associated to glycoprotein P including diltiazem&#44; verapamil&#44; atorvastatin&#44; etc&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a> Recently&#44; Ruff et al&#46; published the results of a study that pooled the available information from phase III studies on the use of NOAs&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> The conclusions of the authors underscored the benefits of these new drug substances&#46; However&#44; despite the large sample size of the metaanalysis &#40;71&#44;683 patients&#41;&#44; we consider that it has a number of methodological limitations&#46; On one hand&#44; the populations in each study were not analogous in terms of cardiovascular risk and the probability of embolic events &#40;as assessed using the CHADS<span class="elsevierStyleInf">2</span> classification&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a> On the other hand&#44; the different NOAs cannot be pooled as a &#8220;single drug&#8221; versus warfarin&#58; in effect&#44; as can be seen in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; not all the NOAs have the same characteristics and therapeutic targets&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Independent of the above&#44; the main problem with NOAs is the control of bleeding after severe trauma&#46; The current recommendations on reversion of the effect of these drugs are set within the context of scheduled surgery and other procedures&#44; though in the case of conditions as common as trauma&#44; special care is required&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">7&#44;18&#44;19</span></a> In this respect&#44; activated charcoal is advised if the NOA was administered in the previous 2<span class="elsevierStyleHsp" style=""></span>h&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#44;7&#44;20</span></a> In the case of dabigatran&#44; the Summary of Product Characteristics contemplates the possibility of extrarenal filtration&#44; since 68&#37; of the drug is dialyzable&#46; However&#44; this is complicated to do in severe trauma patients&#44; since a specific vascular access would be needed for the dialysis technique&#44; with the patient under anticoagulation&#46; Likewise&#44; the available time window is not enough to allow complete elimination of the drug&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">20&#8211;23</span></a> Of note is the fact that fresh frozen plasma &#40;FFP&#41; does not revert thrombin inhibition&#46; Therefore&#44; since it does not improve patient coagulopathy&#44; we consider the recommendation of the European Heart Rhythm Association regarding the use of FFP as a volume expander to be questionable&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The latest European guides on the management of bleeding and coagulopathy related to trauma offer a series of recommendations referred to patients receiving anticoagulation therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> In this regard&#44; the early use of prothrombin complex concentrate &#40;PCC&#41; for the emergent reversion of patients anticoagulated with vitamin K-dependent drugs is advised &#40;grade 1B recommendation&#41;&#46; The guides indicate that if this strategy is followed&#44; PCC should be administered with thromboelastometric evidence of a delay in the activation of coagulation &#40;grade 2C recommendation&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> If the patient is being treated with NOAs&#44; the PCC dose must be greater and should be established on an individualized basis&#44; weighing thromboembolic risk against the need for rapid and effective correction of such induced coagulopathy&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#44;24&#8211;27</span></a> Recommendation number 32 of the European guides suggests the control of anti-Factor Xa activity in patients treated with rivaroxaban&#44; apixaban or edoxaban &#40;grade 2C recommendation&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> If bleeding is considered to be life-threatening&#44; the reversion of rivaroxaban&#44; apixaban and edoxaban with high-dose PCC &#40;25&#8211;50<span class="elsevierStyleHsp" style=""></span>U&#47;kg&#41; is advised &#40;grade 2C recommendation&#41;&#46; Treatment with Factor IIa antagonists &#40;dabigatran&#41; prolongs activated partial thromboplastin time &#40;aPTT&#41; and thrombin time&#8211;high PCC doses being inefficient in such situations &#40;grade 2B recommendation&#41;&#46; In these cases the participation of an experienced hematologist is advised&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> Accordingly&#44; specific treatment should be provided to revert the effects upon Factor IIa&#46; In the case of recombinant activated Factor VII &#40;rFVIIa&#41;&#44; the guides recommend &#40;recommendation 33&#41; consideration of its use after serious bleeding&#44; and if the traumatic coagulopathy persists despite conventional attempts to control the bleeding&#44; in the absence of secondary intracranial hemorrhage following isolated traumatic brain injury &#40;grade 2C recommendation&#41;&#46; However&#44; the guides make no specific mention of the use of rFVIIa in the context of patients under treatment with NOAs&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> From the clinical perspective&#44; it must be remembered that NOA interruption or reversion can imply an increased thrombotic risk&#44; because of the shorter drug half-life and the use of pro-hemostatic agents&#44; which are not true antidotes to such drugs &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">In conclusion&#44; aging of the population is associated to an increased prevalence of age-related disorders such as atrial fibrillation&#44; the management of which is in constant evolution&#46; The use of NOAs has opened new perspectives in the prevention of ischemic stroke in patients with AF or other emboligenic processes&#44; though on the other hand they indirectly increase the probability of having to deal in hospital with NOA-anticoagulated trauma patients&#46; At present we are in the wait of development of drugs or monoclonal antibodies such as idarucizumab &#40;ClinicalTrials&#46;gov identifier&#58; NCT02104947&#41;&#44; to antagonize the effects of NOAS and thus allow good overall control of treatment with these new oral anticoagulants and optimization of their use in all possible scenarios&#46;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">28&#8211;30</span></a> Once specific measures for NOA reversion after severe trauma become available&#44; we probably will have overcome the major problem of bleeding management in patients of this kind upon admission to hospital&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conflicts of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:6 [
        0 => array:3 [
          "identificador" => "xres475185"
          "titulo" => "Abstract"
          "secciones" => array:1 [
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              "identificador" => "abst0005"
            ]
          ]
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        1 => array:2 [
          "identificador" => "xpalclavsec497266"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres475186"
          "titulo" => "Resumen"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0010"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec497265"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Conflicts of interest"
        ]
        5 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2014-07-06"
    "fechaAceptado" => "2014-09-10"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec497266"
          "palabras" => array:5 [
            0 => "New oral anticoagulants"
            1 => "Trauma"
            2 => "Bleeding"
            3 => "Reversion"
            4 => "Prothrombin complex concentrate"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec497265"
          "palabras" => array:5 [
            0 => "Nuevos anticoagulantes orales"
            1 => "Trauma"
            2 => "Hemorragia"
            3 => "Reversi&#243;n"
            4 => "Complejo concentrado de protrombina"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The high incidence of trauma&#44; especially in elderly people anticoagulated with new oral anticoagulants &#40;NOAs&#41;&#44; has become a major challenge&#44; particularly in critical situations with life-threatening bleeding&#46; Under these circumstances&#44; urgent NOA reversion becomes mandatory&#46; Prothrombin complex has become a frequent indication in critical situations in which rapid reversal of anticoagulation is needed and where the use of fresh frozen plasma is limited&#46; This study offers our point of view regarding the usefulness of NOAs&#44; not only in the prevention of cardioembolic events but also as regards their emergent reversion in cases of severe bleeding associated to trauma&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La alta incidencia de los traumatismos&#44; especialmente en aquella poblaci&#243;n mayor previamente anticoagulada con nuevos anticoagulantes orales &#40;NACO&#41;&#44; se ha convertido en un gran desaf&#237;o&#44; sobre todo en aquellas situaciones cr&#237;ticas en las que existe una hemorragia grave que pueda comprometer la vida del paciente&#46; En estos casos se hace necesaria la aplicaci&#243;n urgente de medidas de reversi&#243;n&#46; El empleo de complejo protromb&#237;nico es una indicaci&#243;n cada vez m&#225;s frecuente en estas situaciones de urgencia&#44; en las que se necesita una reversi&#243;n r&#225;pida de la anticoagulaci&#243;n y en las que el uso de plasma fresco congelado es limitado&#46; El objetivo de este trabajo es dar nuestro punto de vista sobre la utilidad de los NACO&#44; no solo en la prevenci&#243;n de enfermedades cardioemb&#243;licas&#44; sino en su reversi&#243;n emergente en aquellos casos de hemorragia grave asociada al trauma&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Egea-Guerrero JJ&#44; Quintana D&#237;az M&#46; Nuevos anticoagulantes orales en el paciente traumatizado grave&#58; &#191;enemigo a las puertas&#63; Med Intensiva&#46; 2015&#59;39&#58;167&#8211;171&#46;</p>"
      ]
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        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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        "tabla" => array:3 [
          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">INR&#58; international normalized ratio&#59; PT&#58; prothrombin time&#59; aPTT&#58; activated partial thromboplastin time&#59; TT&#58; thrombin time&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Based on&#58; Lazo-Langner et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a> Connolly et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a> Patel et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a> Granger et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> Giuliano et al&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a></p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Drug&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dabigatran&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Rivaroxaban&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Apixaban&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Edoxaban&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Clinical trial &#40;year&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RE-LY &#40;2009&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ROCKET AF &#40;2010&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ARISTOTLE &#40;2011&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ENGAGE-AF TIMI 48 &#40;2013&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Sample size&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&#46;113&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&#46;264&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&#46;201&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21&#46;105&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Target&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa &#40;thrombin&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Xa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Xa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Xa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Peak concentration &#40;h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#8211;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#8211;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#8211;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#8211;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Half-life &#40;h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#8211;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#8211;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#8211;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#8211;14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="center" valign="top">Effect on laboratory test parameters</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">PT &#40;Quick&#47;Owren methods&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prolonged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prolonged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prolonged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prolonged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">INR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Elevated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Elevated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Elevated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Elevated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">aPTT<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prolonged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prolonged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prolonged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prolonged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Fibrinogen &#40;Clauss method&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Moderately underestimated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Minimum effect&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Minimum effect&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Minimum effect&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">TT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prolonged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Minimum effect&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Minimum effect&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Minimum effect&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Activated Factor X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Minimum effect&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Marked effect&#47;overestimated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Marked effect&#47;overestimated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Marked effect&#47;overestimated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">There are variations depending on the type of reagents used&#46;</p>"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Principal characteristics of the new oral anticoagulants &#40;NOAs&#41;&#46;</p>"
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">PCC&#58; prothrombin complex concentrate&#59; CrCL&#58; creatinine clearance&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Type of bleeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Direct thrombin inhibitors &#40;dabigatran&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">FXa inhibitors &#40;apixaban&#44; edoxaban&#44; rivaroxaban&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Potentially non-fatal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">Determine time of last dose and dosage&#46; Administer activated charcoal if less than 2<span class="elsevierStyleHsp" style=""></span>h have elapsed</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Estimation of hemostatic normalization&#58;&#8226; Normal renal function&#58; 12&#8211;24<span class="elsevierStyleHsp" style=""></span>h&#8226; CrCl 50&#8211;80<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#58; 24&#8211;36<span class="elsevierStyleHsp" style=""></span>h&#8226; CrCl 30&#8211;50<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#58; 36&#8211;48<span class="elsevierStyleHsp" style=""></span>h&#8226; CrCl<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#58; &#8805;48<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Estimation of hemostatic normalization&#58; 12&#8211;24<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">Maintain diuresis</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">Adopt local measures to secure hemostasis</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">Volume replacement</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">Transfusion of red cell concentrates&#44; if necessary</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">Transfusion of platelets in case of thrombocytopenia &#40;&#8804;60&#44;000&#47;l or platelet disorders&#41;</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">General bleeding management in trauma patient</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Consider hemodialysis &#40;65&#37; reduction in 4<span class="elsevierStyleHsp" style=""></span>h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hemoperfusion with activated charcoal is not recommended&#46; No data are available&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Potentially fatal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">All of the above</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">PCC&#58; 25<span class="elsevierStyleHsp" style=""></span>U&#47;kg &#40;may be repeated once or twice&#41;&#46; No clinical evidence</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">Activated PCC&#58; 50<span class="elsevierStyleHsp" style=""></span>IE&#47;kg&#59; maximum 200<span class="elsevierStyleHsp" style=""></span>IE&#47;kg&#47;day&#41;&#58; no significant evidence on its benefit compared with PCC&#46; Can be considered if available before PCC</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">Activated Factor VII &#40;rFVIIa&#59; 90<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#41;&#46; No data on additional benefits&#59; more expensive &#40;evidence only in animals&#41;</td></tr></tbody></table>
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New oral anticoagulants in severe trauma patients: Enemy at the gates?
Nuevos anticoagulantes orales en el paciente traumatizado grave: ¿enemigo a las puertas?
J.J. Egea-Guerreroa,b,
Corresponding author
, M. Quintana Díazc,d
a Neurocritical Care Unit, Critical and Emergency Care Clinical Management Unit, Virgen del Rocío University Hospital, Sevilla, Spain
b Institute of Biomedicine of Seville (IBiS)/CSIC/University of Seville, Seville, Spain
c Emergency Care Department, La Paz University Hospital, IdiPAZ, Madrid, Spain
d Intensive Care Unit, La Paz University Hospital, IdiPAZ, Madrid, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Traumatisms are a serious worldwide public health problem&#46; Although the last World Health Organization &#40;WHO&#41; reports on the importance of trauma are separated by a period of almost 10 years&#44; they continue to alert us to the magnitude and importance of the problem&#44; and its possible future consequences &#40;Document TDR&#47;Gen&#47;96&#46;1&#59; update 2008&#41;&#46; It must be underscored that we are witnessing a change in the epidemiology of trauma&#44; with an increase in the number of accidental falls among elderly people with comorbidities&#8211;a situation that results in increased mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> This scenario points to the need to introduce primary and secondary prevention strategies referred to traumatisms in general&#44; and indicates that care must be optimized in patients who suffer serious injuries&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Bleeding is known to be one of the main causal factors of mortality associated to accidents &#40;30&#8211;40&#37; of all cases&#41;&#46; However&#44; a priori&#44; bleeding produced by trauma should be regarded as a potentially reversible cause of mortality provided surgical damage control measures are adopted or coagulopathy associated to trauma is avoided&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3&#44;4</span></a> Nevertheless&#44; if the patient is under the effects of some anticoagulant medication&#44; the risk of bleeding increases&#8211;especially if anticoagulation cannot be quickly reverted&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Warfarin is prescribed in about 12&#46;8&#37; of the patients in the United States&#44; mostly in elderly individuals over 65 years of age with chronic atrial fibrillation &#40;AF&#41;&#44; with the purpose of avoiding cardioembolic phenomena&#44; among other problems&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> The development and increasingly widespread use of new oral anticoagulants &#40;NOAs&#41; imply a change in management strategy when patients who use these drugs suffer severe bleeding&#44; independently of its spontaneous or traumatic origin&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#44;7</span></a> At present&#44; the lack of effective means for reverting the effects of NOAs in non-scheduled situations such as after traffic accidents&#44; casual falls or aggressions&#44; where a &#8220;wait and see&#8221; approach is not possible&#44; but constitutes the most critical issue regarding these new anticoagulant drugs&#46; Although the half-life of all NOAs is about 12<span class="elsevierStyleHsp" style=""></span>h&#44; there are a number of situations such as those commented above in which we cannot wait for spontaneous reversion of their effects&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#44;7</span></a> In contrast&#44; when classical anticoagulants are used&#44; such as the vitamin K antagonists&#44; their reversion according to the available time window is well known&#46; Such a reversion or antagonization can be performed using vitamin K&#44; fresh frozen plasma &#40;FFP&#41;&#44; or prothrombin complex concentrate &#40;PCC&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">We obviously cannot forget that anticoagulation&#44; in the context of AF&#44; constitutes the main reversible cause of ischemic stroke&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> Since 1972&#44; when Miller Fisher published a series of recommendations on the management of AF&#44; many studies have attempted to define safer strategies for reducing the risk of embolic events&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">8&#44;9</span></a> Between 1989 and 1993 a total of 6 clinical trials evaluated the usefulness of warfarin versus aspirin or placebo in preventing stroke in patients with arrhythmias of this kind&#46; The data obtained from the global 2900 patients enrolled in these trials showed warfarin use to result in a decrease in cardioembolic phenomena&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a> In this regard&#44; we have established the main advantages and problems associated with the use of vitamin K antagonists&#46; As positive aspects&#44; mention must be made of their reasonable cost&#44; good efficacy&#44; the possibility of knowing their effects upon coagulation&#44; the development of point of care devices that facilitate monitoring of treatment efficacy&#44; dosing optimization through patient genetic studies&#44; and the possibility of practically immediate reversion in the event of bleeding or the need to perform some urgent procedure&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a> As inconveniences&#44; the vitamin K antagonists take time in reaching optimum therapeutic levels &#40;24&#8211;72<span class="elsevierStyleHsp" style=""></span>h&#41;&#44; with a narrow target range &#40;INR 2&#8211;3&#41;&#44; a renal clearance of 90&#37;&#44; unpredictable between- and within-patient responses&#44; the existence of interactions with certain foods and other drugs&#44; and a purported inherent increase in bleeding risk&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a> Because of the above&#44; routine monitoring of coagulation becomes mandatory in this group of patients&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The above inconveniences&#44; together with the high worldwide prevalence of AF associated to population aging &#40;between 3 and 4&#37;&#41;&#44; have probably incentivized the study and development of new drugs that optimize and facilitate adequate prevention of cardioembolic phenomena&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> In this regard&#44; since 2009 a total of four large clinical trials on the use of NOAs have been published&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">12&#8211;15</span></a><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarizes the main advantages and properties of these new drugs&#46; Firstly&#44; NOAs have been shown to offer better prevention of ischemic stroke and embolic events compared with warfarin&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">14&#8211;18</span></a> Secondly&#44; a decrease in severe spontaneous bleeding is observed&#44; especially as regards intracranial hemorrhage&#46; However&#44; it must be noted that dabigatran has been associated to an increased risk of gastrointestinal bleeding&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> Their effects do not require monitoring&#44; thereby improving patient comfort &#8211; though this may be a problem in individuals with treatment adherence problems&#46; It must be emphasized that in the case of important bleeding&#44; excessive dosing&#44; or administration before surgery&#44; we can monitor the effects of these drugs upon coagulation&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a> Nevertheless&#44; no laboratory value has yet been found to reliably determine NOA activity&#44; since some specific parameters may be under- or overestimated &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">In the same way as with the classical anticoagulants&#44; NOAs can interact with other drugs associated to glycoprotein P including diltiazem&#44; verapamil&#44; atorvastatin&#44; etc&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a> Recently&#44; Ruff et al&#46; published the results of a study that pooled the available information from phase III studies on the use of NOAs&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> The conclusions of the authors underscored the benefits of these new drug substances&#46; However&#44; despite the large sample size of the metaanalysis &#40;71&#44;683 patients&#41;&#44; we consider that it has a number of methodological limitations&#46; On one hand&#44; the populations in each study were not analogous in terms of cardiovascular risk and the probability of embolic events &#40;as assessed using the CHADS<span class="elsevierStyleInf">2</span> classification&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a> On the other hand&#44; the different NOAs cannot be pooled as a &#8220;single drug&#8221; versus warfarin&#58; in effect&#44; as can be seen in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; not all the NOAs have the same characteristics and therapeutic targets&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Independent of the above&#44; the main problem with NOAs is the control of bleeding after severe trauma&#46; The current recommendations on reversion of the effect of these drugs are set within the context of scheduled surgery and other procedures&#44; though in the case of conditions as common as trauma&#44; special care is required&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">7&#44;18&#44;19</span></a> In this respect&#44; activated charcoal is advised if the NOA was administered in the previous 2<span class="elsevierStyleHsp" style=""></span>h&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#44;7&#44;20</span></a> In the case of dabigatran&#44; the Summary of Product Characteristics contemplates the possibility of extrarenal filtration&#44; since 68&#37; of the drug is dialyzable&#46; However&#44; this is complicated to do in severe trauma patients&#44; since a specific vascular access would be needed for the dialysis technique&#44; with the patient under anticoagulation&#46; Likewise&#44; the available time window is not enough to allow complete elimination of the drug&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">20&#8211;23</span></a> Of note is the fact that fresh frozen plasma &#40;FFP&#41; does not revert thrombin inhibition&#46; Therefore&#44; since it does not improve patient coagulopathy&#44; we consider the recommendation of the European Heart Rhythm Association regarding the use of FFP as a volume expander to be questionable&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The latest European guides on the management of bleeding and coagulopathy related to trauma offer a series of recommendations referred to patients receiving anticoagulation therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> In this regard&#44; the early use of prothrombin complex concentrate &#40;PCC&#41; for the emergent reversion of patients anticoagulated with vitamin K-dependent drugs is advised &#40;grade 1B recommendation&#41;&#46; The guides indicate that if this strategy is followed&#44; PCC should be administered with thromboelastometric evidence of a delay in the activation of coagulation &#40;grade 2C recommendation&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> If the patient is being treated with NOAs&#44; the PCC dose must be greater and should be established on an individualized basis&#44; weighing thromboembolic risk against the need for rapid and effective correction of such induced coagulopathy&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#44;24&#8211;27</span></a> Recommendation number 32 of the European guides suggests the control of anti-Factor Xa activity in patients treated with rivaroxaban&#44; apixaban or edoxaban &#40;grade 2C recommendation&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> If bleeding is considered to be life-threatening&#44; the reversion of rivaroxaban&#44; apixaban and edoxaban with high-dose PCC &#40;25&#8211;50<span class="elsevierStyleHsp" style=""></span>U&#47;kg&#41; is advised &#40;grade 2C recommendation&#41;&#46; Treatment with Factor IIa antagonists &#40;dabigatran&#41; prolongs activated partial thromboplastin time &#40;aPTT&#41; and thrombin time&#8211;high PCC doses being inefficient in such situations &#40;grade 2B recommendation&#41;&#46; In these cases the participation of an experienced hematologist is advised&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> Accordingly&#44; specific treatment should be provided to revert the effects upon Factor IIa&#46; In the case of recombinant activated Factor VII &#40;rFVIIa&#41;&#44; the guides recommend &#40;recommendation 33&#41; consideration of its use after serious bleeding&#44; and if the traumatic coagulopathy persists despite conventional attempts to control the bleeding&#44; in the absence of secondary intracranial hemorrhage following isolated traumatic brain injury &#40;grade 2C recommendation&#41;&#46; However&#44; the guides make no specific mention of the use of rFVIIa in the context of patients under treatment with NOAs&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> From the clinical perspective&#44; it must be remembered that NOA interruption or reversion can imply an increased thrombotic risk&#44; because of the shorter drug half-life and the use of pro-hemostatic agents&#44; which are not true antidotes to such drugs &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">In conclusion&#44; aging of the population is associated to an increased prevalence of age-related disorders such as atrial fibrillation&#44; the management of which is in constant evolution&#46; The use of NOAs has opened new perspectives in the prevention of ischemic stroke in patients with AF or other emboligenic processes&#44; though on the other hand they indirectly increase the probability of having to deal in hospital with NOA-anticoagulated trauma patients&#46; At present we are in the wait of development of drugs or monoclonal antibodies such as idarucizumab &#40;ClinicalTrials&#46;gov identifier&#58; NCT02104947&#41;&#44; to antagonize the effects of NOAS and thus allow good overall control of treatment with these new oral anticoagulants and optimization of their use in all possible scenarios&#46;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">28&#8211;30</span></a> Once specific measures for NOA reversion after severe trauma become available&#44; we probably will have overcome the major problem of bleeding management in patients of this kind upon admission to hospital&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conflicts of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:6 [
        0 => array:3 [
          "identificador" => "xres475185"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec497266"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres475186"
          "titulo" => "Resumen"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0010"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec497265"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Conflicts of interest"
        ]
        5 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2014-07-06"
    "fechaAceptado" => "2014-09-10"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec497266"
          "palabras" => array:5 [
            0 => "New oral anticoagulants"
            1 => "Trauma"
            2 => "Bleeding"
            3 => "Reversion"
            4 => "Prothrombin complex concentrate"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec497265"
          "palabras" => array:5 [
            0 => "Nuevos anticoagulantes orales"
            1 => "Trauma"
            2 => "Hemorragia"
            3 => "Reversi&#243;n"
            4 => "Complejo concentrado de protrombina"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The high incidence of trauma&#44; especially in elderly people anticoagulated with new oral anticoagulants &#40;NOAs&#41;&#44; has become a major challenge&#44; particularly in critical situations with life-threatening bleeding&#46; Under these circumstances&#44; urgent NOA reversion becomes mandatory&#46; Prothrombin complex has become a frequent indication in critical situations in which rapid reversal of anticoagulation is needed and where the use of fresh frozen plasma is limited&#46; This study offers our point of view regarding the usefulness of NOAs&#44; not only in the prevention of cardioembolic events but also as regards their emergent reversion in cases of severe bleeding associated to trauma&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La alta incidencia de los traumatismos&#44; especialmente en aquella poblaci&#243;n mayor previamente anticoagulada con nuevos anticoagulantes orales &#40;NACO&#41;&#44; se ha convertido en un gran desaf&#237;o&#44; sobre todo en aquellas situaciones cr&#237;ticas en las que existe una hemorragia grave que pueda comprometer la vida del paciente&#46; En estos casos se hace necesaria la aplicaci&#243;n urgente de medidas de reversi&#243;n&#46; El empleo de complejo protromb&#237;nico es una indicaci&#243;n cada vez m&#225;s frecuente en estas situaciones de urgencia&#44; en las que se necesita una reversi&#243;n r&#225;pida de la anticoagulaci&#243;n y en las que el uso de plasma fresco congelado es limitado&#46; El objetivo de este trabajo es dar nuestro punto de vista sobre la utilidad de los NACO&#44; no solo en la prevenci&#243;n de enfermedades cardioemb&#243;licas&#44; sino en su reversi&#243;n emergente en aquellos casos de hemorragia grave asociada al trauma&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Egea-Guerrero JJ&#44; Quintana D&#237;az M&#46; Nuevos anticoagulantes orales en el paciente traumatizado grave&#58; &#191;enemigo a las puertas&#63; Med Intensiva&#46; 2015&#59;39&#58;167&#8211;171&#46;</p>"
      ]
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        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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        "tabla" => array:3 [
          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">INR&#58; international normalized ratio&#59; PT&#58; prothrombin time&#59; aPTT&#58; activated partial thromboplastin time&#59; TT&#58; thrombin time&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Based on&#58; Lazo-Langner et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a> Connolly et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a> Patel et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a> Granger et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> Giuliano et al&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a></p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Drug&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dabigatran&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Rivaroxaban&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Apixaban&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Edoxaban&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Clinical trial &#40;year&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RE-LY &#40;2009&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ROCKET AF &#40;2010&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ARISTOTLE &#40;2011&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ENGAGE-AF TIMI 48 &#40;2013&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Sample size&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&#46;113&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&#46;264&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&#46;201&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21&#46;105&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Target&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa &#40;thrombin&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Xa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Xa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Xa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Peak concentration &#40;h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#8211;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#8211;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#8211;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#8211;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Half-life &#40;h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#8211;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#8211;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#8211;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#8211;14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="center" valign="top">Effect on laboratory test parameters</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">PT &#40;Quick&#47;Owren methods&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prolonged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prolonged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prolonged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prolonged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">INR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Elevated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Elevated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Elevated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Elevated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">aPTT<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prolonged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prolonged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prolonged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prolonged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Fibrinogen &#40;Clauss method&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Moderately underestimated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Minimum effect&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Minimum effect&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Minimum effect&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">TT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prolonged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Minimum effect&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Minimum effect&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Minimum effect&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Activated Factor X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Minimum effect&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Marked effect&#47;overestimated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Marked effect&#47;overestimated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Marked effect&#47;overestimated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">There are variations depending on the type of reagents used&#46;</p>"
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          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">PCC&#58; prothrombin complex concentrate&#59; CrCL&#58; creatinine clearance&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Type of bleeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Direct thrombin inhibitors &#40;dabigatran&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">FXa inhibitors &#40;apixaban&#44; edoxaban&#44; rivaroxaban&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Potentially non-fatal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">Determine time of last dose and dosage&#46; Administer activated charcoal if less than 2<span class="elsevierStyleHsp" style=""></span>h have elapsed</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Estimation of hemostatic normalization&#58;&#8226; Normal renal function&#58; 12&#8211;24<span class="elsevierStyleHsp" style=""></span>h&#8226; CrCl 50&#8211;80<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#58; 24&#8211;36<span class="elsevierStyleHsp" style=""></span>h&#8226; CrCl 30&#8211;50<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#58; 36&#8211;48<span class="elsevierStyleHsp" style=""></span>h&#8226; CrCl<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#58; &#8805;48<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Estimation of hemostatic normalization&#58; 12&#8211;24<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">Maintain diuresis</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">Adopt local measures to secure hemostasis</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">Volume replacement</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">Transfusion of red cell concentrates&#44; if necessary</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">Transfusion of platelets in case of thrombocytopenia &#40;&#8804;60&#44;000&#47;l or platelet disorders&#41;</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">General bleeding management in trauma patient</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Consider hemodialysis &#40;65&#37; reduction in 4<span class="elsevierStyleHsp" style=""></span>h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hemoperfusion with activated charcoal is not recommended&#46; No data are available&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Potentially fatal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">All of the above</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">PCC&#58; 25<span class="elsevierStyleHsp" style=""></span>U&#47;kg &#40;may be repeated once or twice&#41;&#46; No clinical evidence</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">Activated PCC&#58; 50<span class="elsevierStyleHsp" style=""></span>IE&#47;kg&#59; maximum 200<span class="elsevierStyleHsp" style=""></span>IE&#47;kg&#47;day&#41;&#58; no significant evidence on its benefit compared with PCC&#46; Can be considered if available before PCC</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">Activated Factor VII &#40;rFVIIa&#59; 90<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#41;&#46; No data on additional benefits&#59; more expensive &#40;evidence only in animals&#41;</td></tr></tbody></table>
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Article information
ISSN: 21735727
Original language: English
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Idiomas
Medicina Intensiva (English Edition)
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¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?