Special article
Clinical efficacy of fresh frozen plasma compared with coagulation factor concentrates for treating coagulopathy in patients with massive bleeding
Eficacia clínica del plasma fresco congelado frente a concentrado de factores de coagulación en el tratamiento de la coagulopatía de pacientes con hemorragia masiva
S. Kozek-Langenecker
Department of Anaesthesia and Intensive Care, Evangelical Hospital Vienna, Hans-Sachs-Gasse 10-12, 1180 Vienna, Austria
Read
9369
Timeswas read the article
2650
Total PDF
6719
Total HTML
Share statistics
array:22 [ "pii" => "S2173572716300315" "issn" => "21735727" "doi" => "10.1016/j.medine.2016.07.001" "estado" => "S300" "fechaPublicacion" => "2016-08-01" "aid" => "887" "copyrightAnyo" => "2016" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Intensiva. 2016;40:371-3" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1984 "formatos" => array:3 [ "EPUB" => 139 "HTML" => 1232 "PDF" => 613 ] ] "itemSiguiente" => array:17 [ "pii" => "S2173572716300297" "issn" => "21735727" "doi" => "10.1016/j.medine.2016.05.001" "estado" => "S300" "fechaPublicacion" => "2016-08-01" "aid" => "933" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Med Intensiva. 2016;40:374-82" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2446 "formatos" => array:3 [ "EPUB" => 189 "HTML" => 1499 "PDF" => 758 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Acute kidney injury: Renal disease in the ICU" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "374" "paginaFinal" => "382" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Lesión renal aguda: nefropatía en la UCI" ] ] "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" => 560 "Ancho" => 943 "Tamanyo" => 61070 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Increase in the number of references obtained in Pubmed since 1990 to 2014, using as key-search acute kidney injury OR acute renal failure OR AKI OR ARF.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "G. Seller-Pérez, S. Más-Font, C. Pérez-Calvo, P. Villa-Díaz, M. Celaya-López, M.E. Herrera-Gutiérrez" "autores" => array:6 [ 0 => array:2 [ "nombre" => "G." "apellidos" => "Seller-Pérez" ] 1 => array:2 [ "nombre" => "S." "apellidos" => "Más-Font" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Pérez-Calvo" ] 3 => array:2 [ "nombre" => "P." "apellidos" => "Villa-Díaz" ] 4 => array:2 [ "nombre" => "M." "apellidos" => "Celaya-López" ] 5 => array:2 [ "nombre" => "M.E." "apellidos" => "Herrera-Gutiérrez" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572716300297?idApp=WMIE" "url" => "/21735727/0000004000000006/v2_201704060203/S2173572716300297/v2_201704060203/en/main.assets" ] "itemAnterior" => array:17 [ "pii" => "S2173572716300303" "issn" => "21735727" "doi" => "10.1016/j.medine.2015.11.003" "estado" => "S300" "fechaPublicacion" => "2016-08-01" "aid" => "865" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Med Intensiva. 2016;40:364-70" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1972 "formatos" => array:3 [ "EPUB" => 176 "HTML" => 1190 "PDF" => 606 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original</span>" "titulo" => "Design and application of model for training ultrasound-guided vascular cannulation in pediatric patients" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "364" "paginaFinal" => "370" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Diseño y aplicación de un modelo de entrenamiento para la canalización vascular ecoguiada en pacientes pediátricos" ] ] "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" => 1128 "Ancho" => 1801 "Tamanyo" => 217246 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Components of the training model.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "O. Pérez-Quevedo, J.M. López-Álvarez, J.M. Limiñana-Cañal, J.F. Loro-Ferrer" "autores" => array:4 [ 0 => array:2 [ "nombre" => "O." "apellidos" => "Pérez-Quevedo" ] 1 => array:2 [ "nombre" => "J.M." "apellidos" => "López-Álvarez" ] 2 => array:2 [ "nombre" => "J.M." "apellidos" => "Limiñana-Cañal" ] 3 => array:2 [ "nombre" => "J.F." "apellidos" => "Loro-Ferrer" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572716300303?idApp=WMIE" "url" => "/21735727/0000004000000006/v2_201704060203/S2173572716300303/v2_201704060203/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Special article</span>" "titulo" => "Clinical efficacy of fresh frozen plasma compared with coagulation factor concentrates for treating coagulopathy in patients with massive bleeding" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "371" "paginaFinal" => "373" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "S. Kozek-Langenecker" "autores" => array:1 [ 0 => array:3 [ "nombre" => "S." "apellidos" => "Kozek-Langenecker" "email" => array:1 [ 0 => "sibylle.kozek@aon.at" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Department of Anaesthesia and Intensive Care, Evangelical Hospital Vienna, Hans-Sachs-Gasse 10-12, 1180 Vienna, Austria" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Eficacia clínica del plasma fresco congelado frente a concentrado de factores de coagulación en el tratamiento de la coagulopatía de pacientes con hemorragia masiva" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Perioperative indication for coagulation factor supplementation</span><p id="par0005" class="elsevierStylePara elsevierViewall">Surgery and massive trauma are frequently associated with significant derangement of haemostatic capacity, caused by loss, consumption, endogenous inhibition (by the protein C pathway), dilution of coagulation factors, and increased clot breakdown (fibrinolysis). Haemostatic therapy in patients without pre-existing haemostatic disorders aims to substitute key components (clotting factors and other blood components) by transfusion of allogeneic blood products, including fresh frozen plasma (FFP), platelet concentrate (PC), red blood cells (RBC) and, in some countries, cryoprecipitate or coagulation factor concentrates. Most commonly, it is not a prophylactic administration of coagulation factors to supranormal levels but rather a correction of critically reduced coagulation factor activity or levels.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Coagulopathy must be fixed fast in order to prevent an aggravating bloody vicious cycle leading to massive bleeding and massive transfusion.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> Of note, fibrinogen is the first coagulation factor to fall to a suboptimal level early during bleeding and dilutional coagulopathy; fibrinogen supplementation is therefore recommended early in patients with relevant bleeding to maintain plasma fibrinogen levels above 1.5–2.0<span class="elsevierStyleHsp" style=""></span>g/L.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Coagulation factors required for thrombin generation fall to suboptimal levels late; prothrombin complex supplementation is therefore not recommended as a first-line therapy in bleeding patients.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Alternatives for coagulation factor supplementation</span><p id="par0010" class="elsevierStylePara elsevierViewall">Typically, standard preparation FFP contains 2.0<span class="elsevierStyleHsp" style=""></span>g/L of fibrinogen (equivalent to 0.6<span class="elsevierStyleHsp" style=""></span>g in a 300<span class="elsevierStyleHsp" style=""></span>mL unit), as well as other pro- and anti-coagulant factors found in plasma, acute phase proteins (cytokines), electrolytes, immunoglobulins and albumin. Concentrations are heterogeneous depending on the donor and mode of preparation.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Pasteurised and lyophilised human fibrinogen concentrate is typically reconstituted in 50<span class="elsevierStyleHsp" style=""></span>mL of sterile water to a final concentration of 20<span class="elsevierStyleHsp" style=""></span>g/L (10 times higher final concentration than FFP). Each vial of fibrinogen concentrate contains about 1.0<span class="elsevierStyleHsp" style=""></span>g of fibrinogen, as well as albumin, <span class="elsevierStyleSmallCaps">l</span>-arginine hydrochloride, sodium chloride and sodium citrate. The concentrated dose of fibrinogen provided by fibrinogen concentrate could be preferable to FFP for restoring plasma fibrinogen levels because of its rapid availability (no thawing), reduced volume (faster infusion times) and increased safety, and has recently been suggested to be more effective than administration of FFP.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Prothrombin complex concentrates (PCC) contain coagulation factors II, VII, IX and X in concentrations depending on the manufacturing process but higher than in FFP. In perioperative bleeding PCC containing activated coagulation factors (factor eight bypassing activity) is not routinely used.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Clinical routine despite poor efficacy</span><p id="par0025" class="elsevierStylePara elsevierViewall">Clinical use of FFP in component therapy has increased over the past four decades. Reports of the success of high FFP:RBC ratios may be responsible for some of this rise. The benefits of any intervention should outweigh the risks: FFP has been associated with increased risk of morbidity and mortality.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> The evidence to support the effectiveness of FFP in the perioperative setting or its appropriate dosing in the massive transfusion setting has been questioned<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,5</span></a>: Previous systematic reviews concluded that efficacy of FFP was inconsistent across all assessed outcomes. Overall, FFP showed a positive effect for 28% and a negative effect for 22% of outcomes. There was limited evidence that FFP reduced mortality: 50% of outcomes associated FFP with reduced mortality (typically trauma/massive bleeding), while 20% were associated with increased mortality (typically surgical/non-massive bleeding). The evidence for the efficacy of fibrinogen concentrate was consistently positive with no negative effects reported. When comparing FFP against fibrinogen concentrate the latter was superior for >50% of outcomes in terms of reducing blood loss, allogeneic transfusion requirements, length of intensive care unit and hospital stay, and increasing plasma fibrinogen levels. A Cochrane review assessed the use of fibrinogen concentrate in bleeding patients with the conclusion that it seems to reduce transfusion requirements but further studies are warranted to demonstrate its harms and benefits.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> However, it should be noted that there is currently no evidence that other therapies, such as therapeutic plasma or cryoprecipitate, are safer or more effective in the setting of acquired bleeding.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Clinical effectiveness of FFP is inferior to PCC, e.g. in the clinical scenario of warfarin reversal.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Evidence is lacking comparing the efficacy of FFP versus PCC in restoring thrombin generation if reduced in massive bleeding. There are no factor concentrates currently available, e.g. for coagulation factor V, XI. After massive transfusion, replacement of these enzymes can only be achieved by FFP transfusion.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">7,8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">From the perspective of the best available scientific evidence the conclusion could be as follows: the weight of evidence does not appear to support the clinical effectiveness of FFP for surgical/massive trauma patients, and suggests it can be detrimental. According to evidence-based medicine methodology it would be rational to recommending that FFP should not be used outside clinical trials for fibrinogen and prothombin complex substitution until further data demonstrate the applicability of plasma to treat coagulopathy in bleeding patients. Currently, 4 randomised controlled trials investigating the efficacy and safety of therapeutic plasma in comparison with other available choices of haemostatic therapy for fibrinogen supplementation are ongoing; no data have been released as yet.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Volume therapy in severe bleeding</span><p id="par0040" class="elsevierStylePara elsevierViewall">Massive transfusion ratio-driven protocols deliver per each combination of 1 unit of FFP, RBC and PC about 600<span class="elsevierStyleHsp" style=""></span>mL. Reconstitution of these 3 allogeneic blood products results in dilution of erythrocytes, platelets and fibrinogen levels<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a>; adequate and timely correction of coagulopathy is not feasible. Absolute hypovolaemia due to blood loss is not a recommended indication for FFP<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a>; safer alternatives with colloidal/crystalloidal solutions exist.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> The European trauma guidelines recommend that plasma transfusion be avoided in patients without substantial bleeding (Grade 1B); irrespective of hypovolaemia.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> Recent data on beneficial effects of FFP on the glycocalyx lack the head-to-head comparison with albumin and synthetic colloidal solution which also have been shown to protect the endothelial lining.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Cost-effectiveness</span><p id="par0045" class="elsevierStylePara elsevierViewall">Cost-effectiveness of a FFP ratio-driven transfusion protocol has not been investigated yet.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Implementation of monitoring-guided goal-directed management algorithms primarily using clotting factor concentrates while avoiding allogeneic blood products including FFP can reduce costs in trauma, cardiac surgery and liver transplantation.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Noteworthy, overall costs have been found to be reduced despite higher direct costs for clotting factor concentrates and viscoelastic tests.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusion and outlook</span><p id="par0050" class="elsevierStylePara elsevierViewall">There is a paucity of high-quality evidence reporting the clinical effectiveness of FFP in a perioperative or massive trauma setting, despite the long period of its usage. Controlled trials with robust blinding and randomisation procedures are warranted.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Currently, FFP is overused, FFP is abused for volume replacement, adequate laboratory parameters for assessing the indication for haemostatic therapy are underused (e.g. fibrinogen level or fibrinogen polymerisation; thrombin generation potential), adverse outcomes and harms related to plasma transfusion are not monitored and ignored.</p><p id="par0060" class="elsevierStylePara elsevierViewall">An individualised, rational plasma transfusion behaviour with careful monitoring of indication, efficacy (e.g. laboratory parameters before and after transfusion), as well as side effects could help improving quality of care and patient safety.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Final recommendations on when to use plasma and when coagulation factor concentrates are summarized in the table.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conflicts of interest</span><p id="par0070" class="elsevierStylePara elsevierViewall">SKL has received travel reimbursement and speakers fees for lecturing from Biotest, Octapharma, Baxter and CSL Behring; travel reimbursement and honoraria for consulting at a Biotest advisory board; and unrestricted educational grants for the e-learning platform, ‘perioperative bleeding’, from CSL Behring among others.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Perioperative indication for coagulation factor supplementation" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Alternatives for coagulation factor supplementation" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Clinical routine despite poor efficacy" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Volume therapy in severe bleeding" ] 4 => array:2 [ "identificador" => "sec0025" "titulo" => "Cost-effectiveness" ] 5 => array:2 [ "identificador" => "sec0030" "titulo" => "Conclusion and outlook" ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Conflicts of interest" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-12-31" "fechaAceptado" => "2016-01-13" "multimedia" => array:1 [ 0 => array:5 [ "identificador" => "tbl0005" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => false "mostrarDisplay" => true "tabla" => array:2 [ "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">Therapeutic goal \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">Fresh frozen plasma \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">Fibrinogen concentrate \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">Prothrombin complex concentrate \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fibrinogen supplementation \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><td class="td" title="table-entry " align="left" valign="top">X \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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Prothrombin complex supplementation \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><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">X \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Coagulation factor V, XI or ADAMTS 13 supplementation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">X \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><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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Multi-coagulation factor supplementation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">X \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><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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Reversal of vitamin K oral anticoagulants \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><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">X \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">“Reversal” of non-vitamin K oral anticoagulants \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><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">(X) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1:1 ratio strategy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">X \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><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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Goal-directed strategy \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><td class="td" title="table-entry " align="left" valign="top">X<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">X<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1387541.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">If respective coagulation factors are detected to be deficient.</p>" ] ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.A. Kozek-Langenecker" 1 => "A. Afshari" 2 => "P. Albaladejo" 3 => "C. Aldecoa Alvarez Santullano" 4 => "E. De Robertis" 5 => "D. Filipescu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/EJA.0b013e32835f4d5b" "Revista" => array:6 [ "tituloSerie" => "Eur J Anaesthesiol" "fecha" => "2013" "volumen" => "30" "paginaInicial" => "270" "paginaFinal" => "382" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23656742" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0060" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Massive transfusion protocols: the role of aggressive resuscitation versus product ratio in mortality reduction" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.J. Riskin" 1 => "T.C. Tsai" 2 => "L. Riskin" 3 => "T. Hernandez-Boussard" 4 => "M. Purtill" 5 => "P.M. Maggio" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jamcollsurg.2009.04.016" "Revista" => array:6 [ "tituloSerie" => "J Am Coll Surg" "fecha" => "2009" "volumen" => "209" "paginaInicial" => "198" "paginaFinal" => "205" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19632596" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0065" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical effectiveness of fresh frozen plasma compared with fibrinogen concentrate: a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S. Kozek-Langenecker" 1 => "B. Sorensen" 2 => "J.R. Hess" 3 => "D.R. Spahn" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/cc10488" "Revista" => array:5 [ "tituloSerie" => "Crit Care" "fecha" => "2011" "volumen" => "15" "paginaInicial" => "R239" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21999308" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0070" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effect of plasma transfusion on morbidity and mortality: a systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.H. Murad" 1 => "J.R. Stubbs" 2 => "M.J. Gandhi" 3 => "A.T. Wang" 4 => "A. Paul" 5 => "P.J. Erwin" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Transfusion (Paris)" "fecha" => "2010" "volumen" => "50" "paginaInicial" => "1370" "paginaFinal" => "1383" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0075" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Is fresh frozen plasma clinically effective? A systematic review of randomized controlled trials" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S.J. Stanworth" 1 => "S.J. Brunskill" 2 => "C.J. Hyde" 3 => "D.B. McClelland" 4 => "M.F. Murphy" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2141.2004.04973.x" "Revista" => array:6 [ "tituloSerie" => "Br J Haematol" "fecha" => "2004" "volumen" => "126" "paginaInicial" => "139" "paginaFinal" => "152" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15198745" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0080" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fibrinogen concentrate in bleeding patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Wikkelsø" 1 => "J. Lunde" 2 => "M. Johansen" 3 => "J. Stensballe" 4 => "J. Wetterslev" 5 => "A.M. Møller" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Cochrane Database Syst Rev" "fecha" => "2013" "volumen" => "8" "paginaInicial" => "CD00886" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0085" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.F. O'Shaughnessy" 1 => "C. Atterbury" 2 => "P. Bolton Maggs" 3 => "M. Murphy" 4 => "D. Thomas" 5 => "S. Yates" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2141.2004.04972.x" "Revista" => array:6 [ "tituloSerie" => "Br J Haematol" "fecha" => "2004" "volumen" => "126" "paginaInicial" => "11" "paginaFinal" => "28" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15198728" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0090" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "Cross-sectional Guidelines for Therapy with Blood Components and Plasma Derivatives Executive Committee of the German Medical Association on the recommendation of the Scientific Advisory Board" ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:2 [ "edicion" => "4th edition" "fecha" => "2009" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0095" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Haemostatic profile of reconstituted blood in a proposed 1:1:1 ratio of packed red blood cells, platelet concentrate and four different plasma preparations" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Ponschab" 1 => "H. Schöchl" 2 => "C. Gabriel" 3 => "S. Süssner" 4 => "J. Cadamuro" 5 => "E. Haschke-Becher" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/anae.13067" "Revista" => array:6 [ "tituloSerie" => "Anaesthesia" "fecha" => "2015" "volumen" => "70" "paginaInicial" => "528" "paginaFinal" => "536" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25866040" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0100" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of bleeding following major trauma: an updated European guideline" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Rossaint" 1 => "B. Bouillon" 2 => "V. Cerny" 3 => "T.J. Coats" 4 => "J. Duranteau" 5 => "E. Fernandez-Mondejar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/cc8943" "Revista" => array:5 [ "tituloSerie" => "Crit Care" "fecha" => "2010" "volumen" => "14" "paginaInicial" => "R52" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20370902" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735727/0000004000000006/v2_201704060203/S2173572716300315/v2_201704060203/en/main.assets" "Apartado" => null "PDF" => "https://static.elsevier.es/multimedia/21735727/0000004000000006/v2_201704060203/S2173572716300315/v2_201704060203/en/main.pdf?idApp=WMIE&text.app=https://medintensiva.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572716300315?idApp=WMIE" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 6 | 14 |
| 2024 October | 105 | 38 | 143 |
| 2024 September | 114 | 37 | 151 |
| 2024 August | 141 | 54 | 195 |
| 2024 July | 136 | 25 | 161 |
| 2024 June | 146 | 54 | 200 |
| 2024 May | 108 | 44 | 152 |
| 2024 April | 74 | 43 | 117 |
| 2024 March | 74 | 30 | 104 |
| 2024 February | 81 | 37 | 118 |
| 2024 January | 111 | 30 | 141 |
| 2023 December | 139 | 48 | 187 |
| 2023 November | 121 | 14 | 135 |
| 2023 October | 138 | 33 | 171 |
| 2023 September | 74 | 34 | 108 |
| 2023 August | 73 | 24 | 97 |
| 2023 July | 74 | 19 | 93 |
| 2023 June | 81 | 29 | 110 |
| 2023 May | 122 | 29 | 151 |
| 2023 April | 88 | 20 | 108 |
| 2023 March | 96 | 37 | 133 |
| 2023 February | 77 | 46 | 123 |
| 2023 January | 87 | 27 | 114 |
| 2022 December | 80 | 36 | 116 |
| 2022 November | 103 | 32 | 135 |
| 2022 October | 87 | 36 | 123 |
| 2022 September | 77 | 40 | 117 |
| 2022 August | 48 | 42 | 90 |
| 2022 July | 46 | 25 | 71 |
| 2022 June | 61 | 39 | 100 |
| 2022 May | 68 | 53 | 121 |
| 2022 April | 95 | 29 | 124 |
| 2022 March | 94 | 67 | 161 |
| 2022 February | 83 | 31 | 114 |
| 2022 January | 117 | 40 | 157 |
| 2021 December | 119 | 54 | 173 |
| 2021 November | 103 | 49 | 152 |
| 2021 October | 95 | 69 | 164 |
| 2021 September | 90 | 47 | 137 |
| 2021 August | 84 | 49 | 133 |
| 2021 July | 77 | 42 | 119 |
| 2021 June | 63 | 34 | 97 |
| 2021 May | 96 | 55 | 151 |
| 2021 April | 198 | 91 | 289 |
| 2021 March | 152 | 33 | 185 |
| 2021 February | 119 | 26 | 145 |
| 2021 January | 167 | 27 | 194 |
| 2020 December | 104 | 25 | 129 |
| 2020 November | 91 | 23 | 114 |
| 2020 October | 73 | 31 | 104 |
| 2020 September | 66 | 25 | 91 |
| 2020 August | 63 | 30 | 93 |
| 2020 July | 71 | 20 | 91 |
| 2020 June | 78 | 20 | 98 |
| 2020 May | 77 | 16 | 93 |
| 2020 April | 115 | 19 | 134 |
| 2020 March | 110 | 17 | 127 |
| 2020 February | 168 | 31 | 199 |
| 2020 January | 51 | 30 | 81 |
| 2019 December | 58 | 21 | 79 |
| 2019 November | 52 | 27 | 79 |
| 2019 October | 66 | 32 | 98 |
| 2019 September | 71 | 29 | 100 |
| 2019 August | 48 | 20 | 68 |
| 2019 July | 31 | 30 | 61 |
| 2019 June | 36 | 23 | 59 |
| 2019 May | 51 | 21 | 72 |
| 2019 April | 52 | 18 | 70 |
| 2019 March | 39 | 33 | 72 |
| 2019 February | 30 | 24 | 54 |
| 2019 January | 32 | 20 | 52 |
| 2018 December | 25 | 42 | 67 |
| 2018 November | 32 | 47 | 79 |
| 2018 October | 45 | 24 | 69 |
| 2018 September | 22 | 4 | 26 |
| 2018 August | 10 | 4 | 14 |
| 2018 July | 18 | 5 | 23 |
| 2018 June | 22 | 5 | 27 |
| 2018 May | 20 | 3 | 23 |
| 2018 April | 16 | 6 | 22 |
| 2018 March | 36 | 3 | 39 |
| 2018 February | 13 | 4 | 17 |
| 2018 January | 15 | 4 | 19 |
| 2017 December | 16 | 6 | 22 |
| 2017 November | 19 | 8 | 27 |
| 2017 October | 17 | 6 | 23 |
| 2017 September | 13 | 4 | 17 |
| 2017 August | 8 | 9 | 17 |
| 2017 July | 14 | 7 | 21 |
| 2017 June | 17 | 5 | 22 |
| 2017 May | 16 | 9 | 25 |
| 2017 April | 16 | 14 | 30 |
| 2017 March | 7 | 2 | 9 |
| 2017 February | 9 | 8 | 17 |
| 2017 January | 10 | 7 | 17 |
| 2016 December | 18 | 18 | 36 |
| 2016 November | 34 | 0 | 34 |
| 2016 October | 3 | 1 | 4 |
| 2016 September | 1 | 1 | 2 |
| 2016 August | 4 | 5 | 9 |
Show all
