was read the article
array:23 [ "pii" => "S2173572715000168" "issn" => "21735727" "doi" => "10.1016/j.medine.2015.03.003" "estado" => "S300" "fechaPublicacion" => "2015-04-01" "aid" => "733" "copyrightAnyo" => "2014" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Intensiva. 2015;39:167-71" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2591 "formatos" => array:3 [ "EPUB" => 187 "HTML" => 1524 "PDF" => 880 ] ] "Traduccion" => array:1 [ "es" => array:18 [ "pii" => "S0210569114002174" "issn" => "02105691" "doi" => "10.1016/j.medin.2014.09.008" "estado" => "S300" "fechaPublicacion" => "2015-04-01" "aid" => "733" "copyright" => "Elsevier España, S.L.U. y SEMICYUC" "documento" => "article" "subdocumento" => "sco" "cita" => "Med Intensiva. 2015;39:167-71" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 5313 "formatos" => array:3 [ "EPUB" => 182 "HTML" => 4000 "PDF" => 1131 ] ] "es" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Punto de vista</span>" "titulo" => "Nuevos anticoagulantes orales en el paciente traumatizado grave: ¿enemigo a las puertas?" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "167" "paginaFinal" => "171" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "New oral anticoagulants in severe trauma patients: Enemy at the gates?" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J.J. Egea-Guerrero, M. Quintana Díaz" "autores" => array:2 [ 0 => array:2 [ "nombre" => "J.J." "apellidos" => "Egea-Guerrero" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Quintana Díaz" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173572715000168" "doi" => "10.1016/j.medine.2015.03.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572715000168?idApp=WMIE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210569114002174?idApp=WMIE" "url" => "/02105691/0000003900000003/v2_201503200650/S0210569114002174/v2_201503200650/es/main.assets" ] ] "itemSiguiente" => array:18 [ "pii" => "S2173572715000144" "issn" => "21735727" "doi" => "10.1016/j.medine.2015.03.001" "estado" => "S300" "fechaPublicacion" => "2015-04-01" "aid" => "727" "documento" => "article" "crossmark" => 1 "subdocumento" => "ssu" "cita" => "Med Intensiva. 2015;39:172-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 3181 "formatos" => array:3 [ "EPUB" => 177 "HTML" => 2312 "PDF" => 692 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "Importance of ventricular function in the election of electro heart mode" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "172" "paginaFinal" => "178" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Importancia de la función ventricular en la elección del modo de electroestimulación cardiaca" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1072 "Ancho" => 2332 "Tamanyo" => 154191 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">(A) Occlusive retrograde venography. (B) Chest X-ray view showing the electrode in the left ventricle.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "S. Nicolás-Franco, F.J. Rodríguez-González, A. Nicolás-Boluda, A. Sánchez-Martos" "autores" => array:4 [ 0 => array:2 [ "nombre" => "S." "apellidos" => "Nicolás-Franco" ] 1 => array:2 [ "nombre" => "F.J." "apellidos" => "Rodríguez-González" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Nicolás-Boluda" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Sánchez-Martos" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0210569114002113" "doi" => "10.1016/j.medin.2014.09.002" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210569114002113?idApp=WMIE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572715000144?idApp=WMIE" "url" => "/21735727/0000003900000003/v2_201504120238/S2173572715000144/v2_201504120238/en/main.assets" ] "itemAnterior" => array:17 [ "pii" => "S2173572715000193" "issn" => "21735727" "doi" => "10.1016/j.medine.2014.04.006" "estado" => "S300" "fechaPublicacion" => "2015-04-01" "aid" => "683" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Med Intensiva. 2015;39:160-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1961 "formatos" => array:3 [ "EPUB" => 163 "HTML" => 1167 "PDF" => 631 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original</span>" "titulo" => "Intramuscular midazolam versus intravenous diazepam for treatment of seizures in the pediatric emergency department: A randomized clinical trial" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "160" "paginaFinal" => "166" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Midazolam intramuscular frente a diazepam intravenoso para el tratamiento de convulsiones en el Servicio de Urgencias Pediátricas: ensayo clínico aleatorizado" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 676 "Ancho" => 1417 "Tamanyo" => 62337 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Study flowchart.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J.L. Portela, P.C.R. Garcia, J.P. Piva, A. Barcelos, F. Bruno, R. Branco, R.C. Tasker" "autores" => array:7 [ 0 => array:2 [ "nombre" => "J.L." "apellidos" => "Portela" ] 1 => array:2 [ "nombre" => "P.C.R." "apellidos" => "Garcia" ] 2 => array:2 [ "nombre" => "J.P." "apellidos" => "Piva" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Barcelos" ] 4 => array:2 [ "nombre" => "F." "apellidos" => "Bruno" ] 5 => array:2 [ "nombre" => "R." "apellidos" => "Branco" ] 6 => array:2 [ "nombre" => "R.C." "apellidos" => "Tasker" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572715000193?idApp=WMIE" "url" => "/21735727/0000003900000003/v2_201504120238/S2173572715000193/v2_201504120238/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Point of view</span>" "titulo" => "New oral anticoagulants in severe trauma patients: Enemy at the gates?" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "167" "paginaFinal" => "171" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "J.J. Egea-Guerrero, M. Quintana Díaz" "autores" => array:2 [ 0 => array:4 [ "nombre" => "J.J." "apellidos" => "Egea-Guerrero" "email" => array:2 [ 0 => "juanjoegea@hotmail.com" 1 => "juanj.egea.sspa@juntadeandalucia.es" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M." "apellidos" => "Quintana Díaz" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Neurocritical Care Unit, Critical and Emergency Care Clinical Management Unit, Virgen del Rocío University Hospital, Sevilla, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Institute of Biomedicine of Seville (IBiS)/CSIC/University of Seville, Seville, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Emergency Care Department, La Paz University Hospital, IdiPAZ, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Intensive Care Unit, La Paz University Hospital, IdiPAZ, Madrid, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Nuevos anticoagulantes orales en el paciente traumatizado grave: ¿enemigo a las puertas?" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Traumatisms are a serious worldwide public health problem. Although the last World Health Organization (WHO) reports on the importance of trauma are separated by a period of almost 10 years, they continue to alert us to the magnitude and importance of the problem, and its possible future consequences (Document TDR/Gen/96.1; update 2008). It must be underscored that we are witnessing a change in the epidemiology of trauma, with an increase in the number of accidental falls among elderly people with comorbidities–a situation that results in increased mortality.<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, and indicates that care must be optimized in patients who suffer serious injuries.<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 (30–40% of all cases). However, a priori, 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.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3,4</span></a> Nevertheless, if the patient is under the effects of some anticoagulant medication, the risk of bleeding increases–especially if anticoagulation cannot be quickly reverted.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Warfarin is prescribed in about 12.8% of the patients in the United States, mostly in elderly individuals over 65 years of age with chronic atrial fibrillation (AF), with the purpose of avoiding cardioembolic phenomena, among other problems.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> The development and increasingly widespread use of new oral anticoagulants (NOAs) imply a change in management strategy when patients who use these drugs suffer severe bleeding, independently of its spontaneous or traumatic origin.<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6,7</span></a> At present, the lack of effective means for reverting the effects of NOAs in non-scheduled situations such as after traffic accidents, casual falls or aggressions, where a “wait and see” approach is not possible, but constitutes the most critical issue regarding these new anticoagulant drugs. Although the half-life of all NOAs is about 12<span class="elsevierStyleHsp" style=""></span>h, there are a number of situations such as those commented above in which we cannot wait for spontaneous reversion of their effects.<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6,7</span></a> In contrast, when classical anticoagulants are used, such as the vitamin K antagonists, their reversion according to the available time window is well known. Such a reversion or antagonization can be performed using vitamin K, fresh frozen plasma (FFP), or prothrombin complex concentrate (PCC).<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">We obviously cannot forget that anticoagulation, in the context of AF, constitutes the main reversible cause of ischemic stroke.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> Since 1972, when Miller Fisher published a series of recommendations on the management of AF, many studies have attempted to define safer strategies for reducing the risk of embolic events.<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">8,9</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. The data obtained from the global 2900 patients enrolled in these trials showed warfarin use to result in a decrease in cardioembolic phenomena.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a> In this regard, we have established the main advantages and problems associated with the use of vitamin K antagonists. As positive aspects, mention must be made of their reasonable cost, good efficacy, the possibility of knowing their effects upon coagulation, the development of point of care devices that facilitate monitoring of treatment efficacy, dosing optimization through patient genetic studies, and the possibility of practically immediate reversion in the event of bleeding or the need to perform some urgent procedure.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a> As inconveniences, the vitamin K antagonists take time in reaching optimum therapeutic levels (24–72<span class="elsevierStyleHsp" style=""></span>h), with a narrow target range (INR 2–3), a renal clearance of 90%, unpredictable between- and within-patient responses, the existence of interactions with certain foods and other drugs, and a purported inherent increase in bleeding risk.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a> Because of the above, routine monitoring of coagulation becomes mandatory in this group of patients.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The above inconveniences, together with the high worldwide prevalence of AF associated to population aging (between 3 and 4%), have probably incentivized the study and development of new drugs that optimize and facilitate adequate prevention of cardioembolic phenomena.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> In this regard, since 2009 a total of four large clinical trials on the use of NOAs have been published.<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">12–15</span></a><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarizes the main advantages and properties of these new drugs. Firstly, NOAs have been shown to offer better prevention of ischemic stroke and embolic events compared with warfarin.<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">14–18</span></a> Secondly, a decrease in severe spontaneous bleeding is observed, especially as regards intracranial hemorrhage. However, it must be noted that dabigatran has been associated to an increased risk of gastrointestinal bleeding.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> Their effects do not require monitoring, thereby improving patient comfort – though this may be a problem in individuals with treatment adherence problems. It must be emphasized that in the case of important bleeding, excessive dosing, or administration before surgery, we can monitor the effects of these drugs upon coagulation.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a> Nevertheless, no laboratory value has yet been found to reliably determine NOA activity, since some specific parameters may be under- or overestimated (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">In the same way as with the classical anticoagulants, NOAs can interact with other drugs associated to glycoprotein P including diltiazem, verapamil, atorvastatin, etc.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a> Recently, Ruff et al. published the results of a study that pooled the available information from phase III studies on the use of NOAs.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> The conclusions of the authors underscored the benefits of these new drug substances. However, despite the large sample size of the metaanalysis (71,683 patients), we consider that it has a number of methodological limitations. On one hand, the populations in each study were not analogous in terms of cardiovascular risk and the probability of embolic events (as assessed using the CHADS<span class="elsevierStyleInf">2</span> classification).<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a> On the other hand, the different NOAs cannot be pooled as a “single drug” versus warfarin: in effect, as can be seen in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, not all the NOAs have the same characteristics and therapeutic targets.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Independent of the above, the main problem with NOAs is the control of bleeding after severe trauma. The current recommendations on reversion of the effect of these drugs are set within the context of scheduled surgery and other procedures, though in the case of conditions as common as trauma, special care is required.<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">7,18,19</span></a> In this respect, activated charcoal is advised if the NOA was administered in the previous 2<span class="elsevierStyleHsp" style=""></span>h.<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6,7,20</span></a> In the case of dabigatran, the Summary of Product Characteristics contemplates the possibility of extrarenal filtration, since 68% of the drug is dialyzable. However, this is complicated to do in severe trauma patients, since a specific vascular access would be needed for the dialysis technique, with the patient under anticoagulation. Likewise, the available time window is not enough to allow complete elimination of the drug.<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">20–23</span></a> Of note is the fact that fresh frozen plasma (FFP) does not revert thrombin inhibition. Therefore, since it does not improve patient coagulopathy, we consider the recommendation of the European Heart Rhythm Association regarding the use of FFP as a volume expander to be questionable.<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.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> In this regard, the early use of prothrombin complex concentrate (PCC) for the emergent reversion of patients anticoagulated with vitamin K-dependent drugs is advised (grade 1B recommendation). The guides indicate that if this strategy is followed, PCC should be administered with thromboelastometric evidence of a delay in the activation of coagulation (grade 2C recommendation).<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> If the patient is being treated with NOAs, the PCC dose must be greater and should be established on an individualized basis, weighing thromboembolic risk against the need for rapid and effective correction of such induced coagulopathy.<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6,24–27</span></a> Recommendation number 32 of the European guides suggests the control of anti-Factor Xa activity in patients treated with rivaroxaban, apixaban or edoxaban (grade 2C recommendation).<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> If bleeding is considered to be life-threatening, the reversion of rivaroxaban, apixaban and edoxaban with high-dose PCC (25–50<span class="elsevierStyleHsp" style=""></span>U/kg) is advised (grade 2C recommendation). Treatment with Factor IIa antagonists (dabigatran) prolongs activated partial thromboplastin time (aPTT) and thrombin time–high PCC doses being inefficient in such situations (grade 2B recommendation). In these cases the participation of an experienced hematologist is advised.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> Accordingly, specific treatment should be provided to revert the effects upon Factor IIa. In the case of recombinant activated Factor VII (rFVIIa), the guides recommend (recommendation 33) consideration of its use after serious bleeding, and if the traumatic coagulopathy persists despite conventional attempts to control the bleeding, in the absence of secondary intracranial hemorrhage following isolated traumatic brain injury (grade 2C recommendation). However, the guides make no specific mention of the use of rFVIIa in the context of patients under treatment with NOAs.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> From the clinical perspective, it must be remembered that NOA interruption or reversion can imply an increased thrombotic risk, because of the shorter drug half-life and the use of pro-hemostatic agents, which are not true antidotes to such drugs (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">In conclusion, aging of the population is associated to an increased prevalence of age-related disorders such as atrial fibrillation, the management of which is in constant evolution. The use of NOAs has opened new perspectives in the prevention of ischemic stroke in patients with AF or other emboligenic processes, though on the other hand they indirectly increase the probability of having to deal in hospital with NOA-anticoagulated trauma patients. At present we are in the wait of development of drugs or monoclonal antibodies such as idarucizumab (ClinicalTrials.gov identifier: NCT02104947), 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.<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">28–30</span></a> Once specific measures for NOA reversion after severe trauma become available, we probably will have overcome the major problem of bleeding management in patients of this kind upon admission to hospital.</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.</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 => "Reversión" 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, especially in elderly people anticoagulated with new oral anticoagulants (NOAs), has become a major challenge, particularly in critical situations with life-threatening bleeding. Under these circumstances, urgent NOA reversion becomes mandatory. 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. This study offers our point of view regarding the usefulness of NOAs, not only in the prevention of cardioembolic events but also as regards their emergent reversion in cases of severe bleeding associated to trauma.</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, especialmente en aquella población mayor previamente anticoagulada con nuevos anticoagulantes orales (NACO), se ha convertido en un gran desafío, sobre todo en aquellas situaciones críticas en las que existe una hemorragia grave que pueda comprometer la vida del paciente. En estos casos se hace necesaria la aplicación urgente de medidas de reversión. El empleo de complejo protrombínico es una indicación cada vez más frecuente en estas situaciones de urgencia, en las que se necesita una reversión rápida de la anticoagulación y en las que el uso de plasma fresco congelado es limitado. El objetivo de este trabajo es dar nuestro punto de vista sobre la utilidad de los NACO, no solo en la prevención de enfermedades cardioembólicas, sino en su reversión emergente en aquellos casos de hemorragia grave asociada al trauma.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as: Egea-Guerrero JJ, Quintana Díaz M. Nuevos anticoagulantes orales en el paciente traumatizado grave: ¿enemigo a las puertas? Med Intensiva. 2015;39:167–171.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">INR: international normalized ratio; PT: prothrombin time; aPTT: activated partial thromboplastin time; TT: thrombin time.</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Based on: Lazo-Langner et al.,<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a> Connolly et al.,<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a> Patel et al.,<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a> Granger et al.,<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> Giuliano et al.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a></p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <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 \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 \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 \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 \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 \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 (year) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RE-LY (2009) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ROCKET AF (2010) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ARISTOTLE (2011) \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 (2013) \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18.113 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14.264 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18.201 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21.105 \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IIa (thrombin) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Xa \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Xa \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Xa \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 (h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1–3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2–4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1–4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1–2 \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 (h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12–17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5–13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8–15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10–14 \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 (Quick/Owren methods) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prolonged \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prolonged \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prolonged \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prolonged \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Elevated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Elevated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Elevated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Elevated \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> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prolonged \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prolonged \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prolonged \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prolonged \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 (Clauss method) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderately underestimated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Minimum effect \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Minimum effect \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Minimum effect \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prolonged \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Minimum effect \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Minimum effect \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Minimum effect \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Minimum effect \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Marked effect/overestimated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Marked effect/overestimated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Marked effect/overestimated \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab748347.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">There are variations depending on the type of reagents used.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Principal characteristics of the new oral anticoagulants (NOAs).</p>" ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">PCC: prothrombin complex concentrate; CrCL: creatinine clearance.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <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">Type of bleeding \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 (dabigatran) \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 (apixaban, edoxaban, rivaroxaban) \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 \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. 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"> \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:• Normal renal function: 12–24<span class="elsevierStyleHsp" style=""></span>h• CrCl 50–80<span class="elsevierStyleHsp" style=""></span>ml/min: 24–36<span class="elsevierStyleHsp" style=""></span>h• CrCl 30–50<span class="elsevierStyleHsp" style=""></span>ml/min: 36–48<span class="elsevierStyleHsp" style=""></span>h• CrCl<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>ml/min: ≥48<span class="elsevierStyleHsp" style=""></span>h \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: 12–24<span class="elsevierStyleHsp" style=""></span>h \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"> \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"> \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"> \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"> \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, if necessary</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \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 (≤60,000/l or platelet disorders)</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \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"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Consider hemodialysis (65% reduction in 4<span class="elsevierStyleHsp" style=""></span>h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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"> \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. No data are available \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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 \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"> \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: 25<span class="elsevierStyleHsp" style=""></span>U/kg (may be repeated once or twice). No clinical evidence</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \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: 50<span class="elsevierStyleHsp" style=""></span>IE/kg; maximum 200<span class="elsevierStyleHsp" style=""></span>IE/kg/day): no significant evidence on its benefit compared with PCC. Can be considered if available before PCC</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \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 (rFVIIa; 90<span class="elsevierStyleHsp" style=""></span>μg/kg). No data on additional benefits; more expensive (evidence only in animals)</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab748348.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Possible measures in the event of bleeding with the new oral anticoagulants (NOAs).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0155" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Injuries" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R. Norton" 1 => "O. Kobusingye" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMra1109343" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2013" "volumen" => "368" "paginaInicial" => "1723" "paginaFinal" => "1730" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23635052" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0160" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Health and economic benefits of improved injury prevention and trauma care worldwide" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Kotagal" 1 => "K.J. Agarwal-Harding" 2 => "C. Mock" 3 => "R. Quansah" 4 => "C. Arreola-Risa" 5 => "J.G. Meara" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0091862" "Revista" => array:5 [ "tituloSerie" => "PLOS ONE" "fecha" => "2014" "volumen" => "9" "paginaInicial" => "e91862" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24626472" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0165" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of bleeding and coagulopathy following major trauma: an updated European guideline" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.R. Spahn" 1 => "B. Bouillon" 2 => "V. Cerny" 3 => "T.J. Coats" 4 => "J. Duranteau" 5 => "E. Fernández-Mondéjar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/cc12685" "Revista" => array:5 [ "tituloSerie" => "Crit Care" "fecha" => "2013" "volumen" => "17" "paginaInicial" => "R76" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23601765" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0170" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Resuscitative goals and new strategies in severe trauma management" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.J. Egea-Guerrero" 1 => "M.D. Freire-Aragón" 2 => "A. Serrano-Lázaro" 3 => "M. Quintana" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.medin.2014.06.003" "Revista" => array:2 [ "tituloSerie" => "Med Intensiva" "fecha" => "2014" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0175" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence and out-comes associated with warfarin use in injure adults: an analysis of The National Trauma Databank" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "L.A. Dossett" 1 => "B.A. Cotton" 2 => "M.R. Griffin" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "J Am Coll Surg" "fecha" => "2009" "volumen" => "209" "paginaInicial" => "S46" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0180" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical review: clinical management of new oral anticoagulants: a structured review with emphasis on the reversal of bleeding complications" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Lazo-Langner" 1 => "E.S. Lang" 2 => "J. Douketis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/cc12592" "Revista" => array:6 [ "tituloSerie" => "Crit Care" "fecha" => "2013" "volumen" => "17" "paginaInicial" => "230" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23806169" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1473309913703281" "estado" => "S300" "issn" => "14733099" ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0185" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Heidbuchel" 1 => "P. Verhamme" 2 => "M. Alings" 3 => "M. Antz" 4 => "W. Hacke" 5 => "J. Oldgren" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/europace/eut083" "Revista" => array:6 [ "tituloSerie" => "Europace" "fecha" => "2013" "volumen" => "15" "paginaInicial" => "625" "paginaFinal" => "651" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23625942" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0190" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment of chronic atrial fibrillation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "C.M. Fisher" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Lancet" "fecha" => "1972" "volumen" => "1" "paginaInicial" => "1284" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2897547" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0195" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials" ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Intern Med" "fecha" => "1994" "volumen" => "154" "paginaInicial" => "1449" "paginaFinal" => "1457" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8018000" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0200" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A randomized trial of genotype-guided dosing of warfarin" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Pirmohamed" 1 => "G. Burnside" 2 => "N. Eriksson" 3 => "A.L. Jorgensen" 4 => "C.H. Toh" 5 => "T. Nicholson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1311386" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2013" "volumen" => "369" "paginaInicial" => "2294" "paginaFinal" => "2303" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24251363" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0205" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intracranial hemorrhage in atrial fibrillation patients during anticoagulation with warfarin or dabigatran: the RE-LY trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.G. Hart" 1 => "H.C. Diener" 2 => "S. Yang" 3 => "S.J. Connolly" 4 => "L. Wallentin" 5 => "P.A. Reilly" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/STROKEAHA.112.650614" "Revista" => array:6 [ "tituloSerie" => "Stroke" "fecha" => "2012" "volumen" => "43" "paginaInicial" => "1511" "paginaFinal" => "1517" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22492518" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0210" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dabigatran versus warfarin in patients with atrial fibrillation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.J. Connolly" 1 => "M.D. Ezekowitz" 2 => "S. Yusuf" 3 => "J. Eikelboom" 4 => "J. Oldgren" 5 => "A. Parekh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa0905561" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2009" "volumen" => "361" "paginaInicial" => "1139" "paginaFinal" => "1151" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19717844" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0215" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rivaroxaban versus warfarin in nonvalvular atrial fibrillation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.R. Patel" 1 => "K.W. Mahaffey" 2 => "J. Garg" 3 => "G. Pan" 4 => "D.E. Singer" 5 => "W. Hacke" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1009638" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2011" "volumen" => "365" "paginaInicial" => "883" "paginaFinal" => "891" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21830957" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0220" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Apixaban versus warfarin in patients with atrial fibrillation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.B. Granger" 1 => "J.H. Alexander" 2 => "J.J. McMurray" 3 => "R.D. Lopes" 4 => "E.M. Hylek" 5 => "M. Hanna" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1107039" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2011" "volumen" => "365" "paginaInicial" => "981" "paginaFinal" => "992" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21870978" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0225" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Edoxaban versus warfarin in patients with atrial fibrillation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.P. Giugliano" 1 => "C.T. Ruff" 2 => "E. Braunwald" 3 => "S.A. Murphy" 4 => "S.D. Wiviott" 5 => "J.L. Halperin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1310907" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2013" "volumen" => "369" "paginaInicial" => "2093" "paginaFinal" => "2104" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24251359" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0230" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.T. Ruff" 1 => "R.P. Giugliano" 2 => "E. Braunwald" 3 => "E.B. Hoffman" 4 => "N. Deenadayalu" 5 => "M.D. Ezekowitz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(13)62343-0" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2014" "volumen" => "383" "paginaInicial" => "955" "paginaFinal" => "962" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24315724" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0235" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "B.F. Gage" 1 => "A.D. Waterman" 2 => "W. Shannon" 3 => "M. Boechler" 4 => "M.W. Rich" 5 => "M.J. Radford" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "2001" "volumen" => "285" "paginaInicial" => "2864" "paginaFinal" => "2870" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11401607" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0240" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rivaroxaban versus enoxaparin for thromboprophylaxis after total hip or knee arthroplasty: a meta-analysis of randomized controlled trials" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Y.B. Cao" 1 => "J.D. Zhang" 2 => "H. Shen" 3 => "Y.Y. Jiang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00228-010-0889-z" "Revista" => array:6 [ "tituloSerie" => "Eur J Clin Pharmacol" "fecha" => "2010" "volumen" => "66" "paginaInicial" => "1099" "paginaFinal" => "1108" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20812009" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0245" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Perioperative management of patients on new oral anticoagulants" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Lai" 1 => "N. Davidson" 2 => "S.W. Galloway" 3 => "J. Thachil" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/bjs.9485" "Revista" => array:6 [ "tituloSerie" => "Br J Surg" "fecha" => "2014" "volumen" => "101" "paginaInicial" => "742" "paginaFinal" => "749" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24777590" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0250" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "How I treat target-specific oral anticoagulant-associated bleeding" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D.M. Siegal" 1 => "D.A. Garcia" 2 => "M.A. Crowther" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2013-09-529784" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2014" "volumen" => "123" "paginaInicial" => "1152" "paginaFinal" => "1158" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24385535" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0255" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dabigatran etexilate – a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Van Ryn" 1 => "J. Stangier" 2 => "S. Haertter" 3 => "K.H. Liesenfeld" 4 => "W. Wienen" 5 => "M. Feuring" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1160/TH09-11-0758" "Revista" => array:6 [ "tituloSerie" => "Thromb Haemost" "fecha" => "2010" "volumen" => "103" "paginaInicial" => "1116" "paginaFinal" => "1127" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20352166" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0260" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dabigatran etexilate: a new oral thrombin inhibitor" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "G.J. Hankey" 1 => "J.W. Eikelboom" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/CIRCULATIONAHA.110.004424" "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "2011" "volumen" => "123" "paginaInicial" => "1436" "paginaFinal" => "1450" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21464059" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0265" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recombinant factor VIIa (rFVIIa) and hemodialysis to manage massive dabigatran-associated postcardiac surgery bleeding" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "T.E. Warkentin" 1 => "P. Margetts" 2 => "S.J. Connolly" 3 => "A. Lamy" 4 => "C. Ricci" 5 => "J.W. Eikelboom" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2011-11-393587" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2012" "volumen" => "119" "paginaInicial" => "2172" "paginaFinal" => "2174" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22383791" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0270" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety of prothrombin complex concentrates for rapid anticoagulation reversal of vitamin K antagonists. A meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Dentali" 1 => "C. Marchesi" 2 => "M.G. Pierfranceschi" 3 => "M. Crowther" 4 => "D. Garcia" 5 => "E. Hylek" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1160/TH11-01-0052" "Revista" => array:6 [ "tituloSerie" => "Thromb Haemost" "fecha" => "2011" "volumen" => "106" "paginaInicial" => "429" "paginaFinal" => "438" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21800002" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0275" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Novel oral anticoagulants: new challenges for anesthesiologists in bleeding patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D.R. Spahn" 1 => "W. Korte" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/ALN.0b013e318238c070" "Revista" => array:6 [ "tituloSerie" => "Anesthesiology" "fecha" => "2012" "volumen" => "116" "paginaInicial" => "9" "paginaFinal" => "11" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21993157" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0280" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rivaroxaban: quantification by anti-FXa assay and influence on coagulation tests: a study in 9 Swiss laboratories" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L.M. Asmis" 1 => "L. Alberio" 2 => "A. Angelillo-Scherrer" 3 => "W. Korte" 4 => "A. Mendez" 5 => "G. Reber" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.thromres.2011.06.031" "Revista" => array:6 [ "tituloSerie" => "Thromb Res" "fecha" => "2012" "volumen" => "129" "paginaInicial" => "492" "paginaFinal" => "498" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21840043" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0285" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reversibility of the anticoagulant effect of high doses of the direct thrombin inhibitor dabigatran, by recombinant Factor VIIa or activated prothrombin complex concentrate" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J. Van Ryn" 1 => "D. Ruehl" 2 => "H. Priepke" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Haematologica" "fecha" => "2008" "volumen" => "93" "paginaInicial" => "148" ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0290" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Lu" 1 => "F.R. DeGuzman" 2 => "S.J. Hollenbach" 3 => "M.J. Karbarz" 4 => "K. Abe" 5 => "G. Lee" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nm.3102" "Revista" => array:6 [ "tituloSerie" => "Nat Med" "fecha" => "2013" "volumen" => "19" "paginaInicial" => "446" "paginaFinal" => "451" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23455714" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0295" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A specific antidote for dabigatran: functional and structural characterization" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Schiele" 1 => "J. van Ryn" 2 => "K. Canada" 3 => "C. Newsome" 4 => "E. Sepulveda" 5 => "J. Park" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2012-11-468207" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2013" "volumen" => "121" "paginaInicial" => "3554" "paginaFinal" => "3562" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23476049" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0300" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk profiles and antithrombotic treatment of patients newly diagnosed with atrial fibrillation at risk of stroke: perspectives from the international, observational, prospective GARFIELD registry" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.K. Kakkar" 1 => "I. Mueller" 2 => "J.P. Bassand" 3 => "D.A. Fitzmaurice" 4 => "S.Z. Goldhaber" 5 => "S. Goto" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0063479" "Revista" => array:5 [ "tituloSerie" => "PLOS ONE" "fecha" => "2013" "volumen" => "8" "paginaInicial" => "e63479" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23704912" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735727/0000003900000003/v2_201504120238/S2173572715000168/v2_201504120238/en/main.assets" "Apartado" => null "PDF" => "https://static.elsevier.es/multimedia/21735727/0000003900000003/v2_201504120238/S2173572715000168/v2_201504120238/en/main.pdf?idApp=WMIE&text.app=https://medintensiva.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572715000168?idApp=WMIE" ]
Year/Month | Html | Total | |
---|---|---|---|
2024 November | 10 | 8 | 18 |
2024 October | 54 | 46 | 100 |
2024 September | 58 | 37 | 95 |
2024 August | 60 | 35 | 95 |
2024 July | 47 | 34 | 81 |
2024 June | 58 | 42 | 100 |
2024 May | 51 | 31 | 82 |
2024 April | 69 | 45 | 114 |
2024 March | 59 | 28 | 87 |
2024 February | 79 | 38 | 117 |
2024 January | 58 | 33 | 91 |
2023 December | 59 | 31 | 90 |
2023 November | 60 | 48 | 108 |
2023 October | 59 | 35 | 94 |
2023 September | 55 | 37 | 92 |
2023 August | 66 | 17 | 83 |
2023 July | 77 | 29 | 106 |
2023 June | 66 | 18 | 84 |
2023 May | 71 | 31 | 102 |
2023 April | 63 | 33 | 96 |
2023 March | 74 | 49 | 123 |
2023 February | 87 | 34 | 121 |
2023 January | 88 | 33 | 121 |
2022 December | 77 | 33 | 110 |
2022 November | 101 | 38 | 139 |
2022 October | 116 | 44 | 160 |
2022 September | 80 | 45 | 125 |
2022 August | 101 | 27 | 128 |
2022 July | 94 | 51 | 145 |
2022 June | 106 | 41 | 147 |
2022 May | 92 | 43 | 135 |
2022 April | 55 | 49 | 104 |
2022 March | 70 | 48 | 118 |
2022 February | 54 | 27 | 81 |
2022 January | 76 | 41 | 117 |
2021 December | 61 | 44 | 105 |
2021 November | 79 | 48 | 127 |
2021 October | 80 | 65 | 145 |
2021 September | 52 | 75 | 127 |
2021 August | 49 | 45 | 94 |
2021 July | 35 | 34 | 69 |
2021 June | 53 | 35 | 88 |
2021 May | 52 | 39 | 91 |
2021 April | 159 | 94 | 253 |
2021 March | 72 | 26 | 98 |
2021 February | 89 | 49 | 138 |
2021 January | 66 | 26 | 92 |
2020 December | 59 | 14 | 73 |
2020 November | 63 | 24 | 87 |
2020 October | 55 | 28 | 83 |
2020 September | 50 | 18 | 68 |
2020 August | 45 | 11 | 56 |
2020 July | 53 | 22 | 75 |
2020 June | 64 | 20 | 84 |
2020 May | 49 | 14 | 63 |
2020 April | 49 | 15 | 64 |
2020 March | 47 | 11 | 58 |
2020 February | 90 | 45 | 135 |
2020 January | 46 | 22 | 68 |
2019 December | 34 | 25 | 59 |
2019 November | 43 | 28 | 71 |
2019 October | 47 | 24 | 71 |
2019 September | 36 | 29 | 65 |
2019 August | 35 | 30 | 65 |
2019 July | 41 | 30 | 71 |
2019 June | 122 | 13 | 135 |
2019 May | 59 | 33 | 92 |
2019 April | 34 | 15 | 49 |
2019 March | 36 | 36 | 72 |
2019 February | 41 | 22 | 63 |
2019 January | 42 | 40 | 82 |
2018 December | 46 | 30 | 76 |
2018 November | 51 | 51 | 102 |
2018 October | 36 | 30 | 66 |
2018 September | 20 | 7 | 27 |
2018 August | 21 | 12 | 33 |
2018 July | 24 | 15 | 39 |
2018 June | 25 | 13 | 38 |
2018 May | 11 | 7 | 18 |
2018 April | 13 | 7 | 20 |
2018 March | 24 | 9 | 33 |
2018 February | 19 | 10 | 29 |
2018 January | 31 | 9 | 40 |
2017 December | 23 | 7 | 30 |
2017 November | 19 | 17 | 36 |
2017 October | 30 | 14 | 44 |
2017 September | 22 | 7 | 29 |
2017 August | 16 | 28 | 44 |
2017 July | 17 | 12 | 29 |
2017 June | 20 | 11 | 31 |
2017 May | 18 | 17 | 35 |
2017 April | 32 | 22 | 54 |
2017 March | 15 | 17 | 32 |
2017 February | 13 | 40 | 53 |
2017 January | 15 | 14 | 29 |
2016 December | 41 | 14 | 55 |
2016 November | 61 | 29 | 90 |
2016 October | 68 | 31 | 99 |
2016 September | 49 | 6 | 55 |
2016 August | 46 | 7 | 53 |
2016 July | 25 | 8 | 33 |