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    "titulo" => "Guided reversal of dabigatran in massive hemorrhagic shock&#58; A case report"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Result of viscoelastic testing &#40;ClotPro&#174;&#41; under the effects of dabigatran&#46; <span class="elsevierStyleBold">EX-test</span>&#58; view of the coagulation process after activation of the extrinsic pathway&#46; <span class="elsevierStyleBold">IN-test</span>&#58; screening test of the intrinsic coagulation pathway&#46; <span class="elsevierStyleBold">FIB-test</span>&#58; detection of functional fibrinogen&#46; <span class="elsevierStyleBold">AP-test</span>&#58; EX-test with the inhibition of fibrinolysis to confirm hyper-fibrinolytic activity&#46; <span class="elsevierStyleBold">HI-test</span>&#58; IN-test with the addition of heparinase to confirm the presence of heparin&#46; <span class="elsevierStyleBold">ECA-test</span>&#58; specific test for direct thrombin antagonists &#40;scantly affected by heparins or direct activated factor X &#40;FXa&#41; antagonists&#41;&#46; <span class="elsevierStyleBold">RVV-test</span>&#58; specific test for direct FXa antagonists&#46; <span class="elsevierStyleBold">Parameters&#58;</span> CT&#58; clotting time&#59; A5 and A10&#58; amplitude 5 and 10&#8239;min after CT&#59; CFT&#58; clot formation time&#59; MCF&#58; maximum clot firmness&#46; Time in seconds &#40;s&#41;&#46; Clot size in millimeters &#40;mm&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Thromboembolic events are a major public health problem&#46; Current clinical practice guidelines preferentially recommend direct oral anticoagulants &#40;DOACs&#41; as the preferred choice for preventing or treating such events in patients with atrial fibrillation or venous thromboembolic disease&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Dabigatran&#44; a direct thrombin inhibitor&#44; is increasingly being used due to its advantages over vitamin K antagonists&#44; including a lower risk of intracranial bleeding&#44; fixed dosing without the need for laboratory monitoring or dietary restrictions&#44; few drug-drug interactions&#44; and a faster onset and offset of pharmacological effects&#44; which makes it easier to plan for invasive procedures&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Patients on DOACs may suffer severe bleeding or need urgent surgery and require a diagnosis with immediate treatment to reverse the anticoagulant effect&#46; As conventional tests take too long to provide results&#44; viscoelastic testing &#40;VET&#41;&#44; which is performed in whole blood and provides results in a few minutes&#44; could prove to be very useful if specific techniques for the detection of DOACs &#40;at levels &#62;50 ng&#47;mL&#41; based on activation with ecarin for anti-IIa &#40;ECA-test&#174;&#41; or with Russell viper venom for anti-Xa &#40;RVV&#8209;test&#174;&#41; are included&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A 62-year-old woman was admitted to the hospital because of a reduced level of consciousness&#46; On arrival at the emergency department&#44; her blood pressure was 80&#47;55 mmHg&#44; and an endoscopy confirmed diffuse bleeding of the gastric mucosa&#44; with a hemoglobin concentration of 4 g&#47;dl on admission&#46; The VET-guided massive transfusion protocol for hemostatic resuscitation was activated&#44; with the transfusion of four units of packed red blood cells and 600 mL of plasma&#44; which failed to control the bleeding&#46; The patient was taking dabigatran at home&#44; so we decided to extend the study with a specific dabigatran test &#40;ECA-Test&#174;&#41;&#44; which confirmed a strong anticoagulant effect of the drug &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; We also measured specific dabigatran levels with the HemosIL&#174; test&#44; which showed a concentration 6 times higher than the upper reference limit &#40;1287 ng&#47;mL&#59; reference limit &#60; 200 ng&#47;mL&#41;&#46; The bleeding was finally controlled after three doses of idarucizumab each&#58; the first dose one hour after onset of the symptoms and the remaining doses every 1&#8211;2 h &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; followed by clinical improvement&#46; Despite bleeding control&#44; the patient died of nosocomial pneumonia after a torpid course in intensive care&#46; The RE&#8209;VERSE AD study concluded that idarucizumab&#44; a monoclonal antibody with high affinity and specificity for dabigatran&#44; quickly and effectively reverts the anticoagulant effect of the latter drug following a single dose&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Its use is rarely needed&#44; except in cases of potentially fatal bleeding or emergent surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> However&#44; in the present case&#44; repeated dosing guided by laboratory tests proved necessary due to the overdosing of dabigatran&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">In conclusion&#44; specific VET provides high sensitivity and specificity in detecting the presence of dabigatran in blood&#44; justifying the use of antidotes&#44; although the use of specific quantitative tests in plasma allows more efficient guidance of administration&#44; as in our case&#44; where the drug was rapidly and specifically detected - confirming the causative agent and the need for idarucizumab&#46;</p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0025" class="elsevierStylePara elsevierViewall">None&#46;</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Author contributions</span><p id="par0020" class="elsevierStylePara elsevierViewall">All the authors contributed to the study conception and design &#40;MFC&#44; MCM&#44; FJRM&#44; AMPM&#41;&#44; data acquisition &#40;MFC&#44; MCM&#44; FJRM&#41; or analysis and interpretation of the data &#40;MCM&#44; FJRM&#41;&#44; and critical review of the intellectual content &#40;MCM&#44; FJRM&#44; AMPM&#41;&#46; All the authors approved the final version of the manuscript submitted for publication&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0030" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Result of viscoelastic testing &#40;ClotPro&#174;&#41; under the effects of dabigatran&#46; <span class="elsevierStyleBold">EX-test</span>&#58; view of the coagulation process after activation of the extrinsic pathway&#46; <span class="elsevierStyleBold">IN-test</span>&#58; screening test of the intrinsic coagulation pathway&#46; <span class="elsevierStyleBold">FIB-test</span>&#58; detection of functional fibrinogen&#46; <span class="elsevierStyleBold">AP-test</span>&#58; EX-test with the inhibition of fibrinolysis to confirm hyper-fibrinolytic activity&#46; <span class="elsevierStyleBold">HI-test</span>&#58; IN-test with the addition of heparinase to confirm the presence of heparin&#46; <span class="elsevierStyleBold">ECA-test</span>&#58; specific test for direct thrombin antagonists &#40;scantly affected by heparins or direct activated factor X &#40;FXa&#41; antagonists&#41;&#46; <span class="elsevierStyleBold">RVV-test</span>&#58; specific test for direct FXa antagonists&#46; <span class="elsevierStyleBold">Parameters&#58;</span> CT&#58; clotting time&#59; A5 and A10&#58; amplitude 5 and 10&#8239;min after CT&#59; CFT&#58; clot formation time&#59; MCF&#58; maximum clot firmness&#46; Time in seconds &#40;s&#41;&#46; Clot size in millimeters &#40;mm&#41;&#46;</p>"
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Before 1st dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Before 2nd dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Before 3rd dose&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">After 3rd dose&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bleeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dabigatran &#40;ng&#47;mL&#41;&#40;30&#8211;225&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#35;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1287&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">269&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">APTT-ratio &#40;0&#46;75&#8211;1&#46;25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;94&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">APTT &#40;s&#41;&#40;24&#46;8&#8211;37&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">143&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">126&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">105&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">INR&#40;0&#46;75&#8211;1&#46;25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
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Articles in press Guided reversal of dabigatran in massive hemorrhagic shock: A case report
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Letter to the Editor
DOI: 10.1016/j.medine.2024.10.002
Available online 25 October 2024
Guided reversal of dabigatran in massive hemorrhagic shock: A case report
Reversión guiada de dabigatrán en un caso de shock hemorrágico masivo
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Manuel Fernández Caroa,
Corresponding author
mfercar@outlook.es

Corresponding author.
, Manuel Casado Méndeza, Francisco Javier Rodríguez Martorellb, Antonio Manuel Puppo Morenoa
a UGC de Cuidados Intensivos, Hospital Universitario Virgen del Rocío, Sevilla, Spain
b UGC de Hematología, Sección de Hemostasia y Trombosis, Hospital Universitario Virgen del Rocío, Sevilla, Spain
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Table 1. Evolution of massive bleeding and severe coagulopathy testing after repeated dosing of idarucizumab 5 g.

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