{
    "abstract": "Optimal transfusion strategies in traumatic hemorrhage are unknown. Reports suggest a beneficial effect of 4-factor prothrombin complex concentrate (4F-PCC) on blood product consumption.\nTo investigate the efficacy and safety of 4F-PCC administration in patients at risk of massive transfusion.\nDouble-blind, randomized, placebo-controlled superiority trial in 12 French designated level I trauma centers from December 29, 2017, to August 31, 2021, involving consecutive patients with trauma at risk of massive transfusion. Follow-up was completed on August 31, 2021.\nIntravenous administration of 1 mL/kg of 4F-PCC (25 IU of factor IX/kg) vs 1 mL/kg of saline solution (placebo). Patients, investigators, and data analysts were blinded to treatment assignment. All patients received early ratio-based transfusion (packed red blood cells:fresh frozen plasma ratio of 1:1 to 2:1) and were treated according to European traumatic hemorrhage guidelines.\nThe primary outcome was 24-hour all blood product consumption (efficacy); arterial or venous thromboembolic events were a secondary outcome (safety).\nOf 4313 patients with the highest trauma level activation, 350 were eligible for emergency inclusion, 327 were randomized, and 324 were analyzed (164 in the 4F-PCC group and 160 in the placebo group). The median (IQR) age of participants was 39 (27-56) years, Injury Severity Score was 36 (26-50 [major trauma]), and admission blood lactate level was 4.6 (2.8-7.4) mmol/L; prehospital arterial systolic blood pressure was less than 90 mm Hg in 179 of 324 patients (59%), 233 patients (73%) were men, and 226 (69%) required expedient hemorrhage control. There was no statistically or clinically significant between-group difference in median (IQR) total 24-hour blood product consumption (12 [5-19] U in the 4F-PCC group vs 11 [6-19] U in the placebo group; absolute difference, 0.2 U [95% CI, -2.99 to 3.33]; P\u2009=\u2009.72). In the 4F-PCC group, 56 patients (35%) presented with at least 1 thromboembolic event vs 37 patients (24%) in the placebo group (absolute difference, 11% [95% CI, 1%-21%]; relative risk, 1.48 [95% CI, 1.04-2.10]; P\u2009=\u2009.03).\nAmong patients with trauma at risk of massive transfusion, there was no significant reduction of 24-hour blood product consumption after administration of 4F-PCC, but thromboembolic events were more common. These findings do not support systematic use of 4F-PCC in patients at risk of massive transfusion.\nClinicalTrials.gov Identifier: NCT03218722.",
    "authors": [
        {
            "affiliation": "Universit\u00e9 Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institute Neurosciences, Grenoble, France.",
            "firstname": "Pierre",
            "initials": "P",
            "lastname": "Bouzat"
        },
        {
            "affiliation": "Trauma Critical Care Unit, Montpellier University Hospital, F-34295 Montpellier Cedex 5, France.",
            "firstname": "Jonathan",
            "initials": "J",
            "lastname": "Charbit"
        },
        {
            "affiliation": "Department of Anesthesiology and Critical Care, Beaujon Hospital, DMU Parabol, AP-HP. Nord, Clichy, France.",
            "firstname": "Paer-Selim",
            "initials": "PS",
            "lastname": "Abback"
        },
        {
            "affiliation": "Department of Anesthesiology and Critical Care, Centre Hospitalier Universitaire Lille, Surgical Critical Care, Lille, France.",
            "firstname": "Delphine",
            "initials": "D",
            "lastname": "Huet-Garrigue"
        },
        {
            "affiliation": "AP-HP, Groupe Hospitalier Universitaire APHP-Sorbonne Universit\u00e9, site Piti\u00e9-Salp\u00eatri\u00e8re, D\u00e9partement d'Anesth\u00e9sie R\u00e9animation, Paris, France.",
            "firstname": "Nathalie",
            "initials": "N",
            "lastname": "Delhaye"
        },
        {
            "affiliation": "Aix Marseille University, Assistance Publique H\u00f4pitaux Universitaires de Marseille, Department of Anesthesiology and Intensive Care Unit, North Hospital, and Centre for CardioVascular and Nutrition Research (C2VN), Inserm 1263, Inrae 1260, Marseille, France.",
            "firstname": "Marc",
            "initials": "M",
            "lastname": "Leone"
        },
        {
            "affiliation": "Hospices Civils de Lyon, Hopital Edouard Herriot, Department of Anesthesia and Intensive Care, Lyon, France.",
            "firstname": "Guillaume",
            "initials": "G",
            "lastname": "Marcotte"
        },
        {
            "affiliation": "University Claude Bernard Lyon 1, INSERM U1290, Research on Healthcare Performance (RESHAPE), and Hospices Civils de Lyon, Groupement Hospitalier Sud, Department of Anesthesia and Intensive Care, Pierre Benite, France.",
            "firstname": "Jean-St\u00e9phane",
            "initials": "JS",
            "lastname": "David"
        },
        {
            "affiliation": "Intensive care unit, Annecy Hospital, Annecy, France.",
            "firstname": "Albrice",
            "initials": "A",
            "lastname": "Levrat"
        },
        {
            "affiliation": "Universit\u00e9 de Nantes, CHU Nantes, P\u00f4le anesth\u00e9sie r\u00e9animations, Service d'Anesth\u00e9sie R\u00e9animation chirurgicale, H\u00f4tel Dieu, Nantes, France.",
            "firstname": "Karim",
            "initials": "K",
            "lastname": "Asehnoune"
        },
        {
            "affiliation": "H\u00f4pitaux Universitaires de Strasbourg, H\u00f4pital de Hautepierre, Service d'Anesth\u00e9sie-R\u00e9animation & M\u00e9decine P\u00e9ri-Op\u00e9ratoire - Universit\u00e9 de Strasbourg, Facult\u00e9 de M\u00e9decine, FMTS, ER3072, Strasbourg, France.",
            "firstname": "Julien",
            "initials": "J",
            "lastname": "Pottecher"
        },
        {
            "affiliation": "D\u00e9partement d'Anesth\u00e9sie-R\u00e9animation, H\u00f4pitaux Universitaires Paris Sud, Universit\u00e9 Paris XI, Facult\u00e9 de M\u00e9decine Paris-Sud, Le Kremlin-Bic\u00eatre, France.",
            "firstname": "Jacques",
            "initials": "J",
            "lastname": "Duranteau"
        },
        {
            "affiliation": "Trauma Critical Care Unit, Montpellier University Hospital, F-34295 Montpellier Cedex 5, France.",
            "firstname": "Elie",
            "initials": "E",
            "lastname": "Courvalin"
        },
        {
            "affiliation": "P\u00f4le d'Anesth\u00e9sie-R\u00e9animation, CHU Grenoble Alpes, Grenoble, France.",
            "firstname": "Anais",
            "initials": "A",
            "lastname": "Adolle"
        },
        {
            "affiliation": "Univ. Grenoble Alpes, CNRS, Public Health department CHU Grenoble Alpes, TIMC-IMAG, Grenoble, France.",
            "firstname": "Dimitri",
            "initials": "D",
            "lastname": "Sourd"
        },
        {
            "affiliation": "Univ. Grenoble Alpes, CNRS, Public Health department CHU Grenoble Alpes, TIMC-IMAG, Grenoble, France.",
            "firstname": "Jean-Luc",
            "initials": "JL",
            "lastname": "Bosson"
        },
        {
            "affiliation": "Sorbonne Universit\u00e9, UMR-S INSERM 1166, IHU ICAN, and Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Department of Emergency medicine and Surgery, Paris, France.",
            "firstname": "Bruno",
            "initials": "B",
            "lastname": "Riou"
        },
        {
            "affiliation": "Department of Anesthesiology and Critical Care, Beaujon Hospital, DMU Parabol, AP-HP. Nord, Clichy, France.",
            "firstname": "Tobias",
            "initials": "T",
            "lastname": "Gauss"
        },
        {
            "affiliation": "Universit\u00e9 Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institute Neurosciences, Grenoble, France.",
            "firstname": "Jean-Fran\u00e7ois",
            "initials": "JF",
            "lastname": "Payen"
        },
        {
            "affiliation": null,
            "firstname": null,
            "initials": null,
            "lastname": null
        }
    ],
    "conclusions": null,
    "copyrights": null,
    "doi": "10.1001/jama.2023.4080\n10.1016/j.injury.2016.10.037\n10.1097/SLA.0000000000004563\n10.1097/SLA.0000000000003657\n10.1007/s00068-022-01998-9\n10.1016/S2352-3026(22)00040-0\n10.1001/jama.2015.12\n10.1016/S2352-3026(17)30077-7\n10.1007/s00134-020-06266-1\n10.1186/cc8948\n10.1186/cc10078\n10.1097/TA.0000000000001938\n10.1097/TA.0000000000002262\n10.1186/s13063-021-05524-x\n10.1186/s13054-015-0835-7\n10.1097/TA.0b013e3181961c35\n10.1111/j.1538-7836.2010.03945.x\n10.1097/SLA.0000000000002825\n10.1016/S0140-6736(11)60278-X\n10.1186/s13054-016-1265-x\n10.1186/s13049-018-0523-0\n10.1007/s00068-019-01165-7\n10.1002/cphy.c170006\n10.1007/s00134-022-06834-7\n10.1111/j.1537-2995.2009.02335.x\n10.1001/jamasurg.2019.5085\n10.1093/bja/aen391\n10.1371/journal.pone.0258192\n10.1136/bmjopen-2021-059181\n10.1001/jamasurg.2019.2884",
    "journal": "JAMA",
    "keywords": [],
    "methods": null,
    "publication_date": "2023-03-22",
    "pubmed_id": "36942533\n27847192\n33065652\n31651535\n35732811\n35271808\n25647203\n28457980\n33048195\n20374650\n21375741\n29664892\n30889141\n34530886\n25887150\n19204506\n20553376\n29794847\n21439633\n27072503\n29986757\n31183527\n29357125\n35925321\n19682336\n31851290\n19168856\n34614035\n36424120\n31461138",
    "results": "Of 4313 patients with the highest trauma level activation, 350 were eligible for emergency inclusion, 327 were randomized, and 324 were analyzed (164 in the 4F-PCC group and 160 in the placebo group). The median (IQR) age of participants was 39 (27-56) years, Injury Severity Score was 36 (26-50 [major trauma]), and admission blood lactate level was 4.6 (2.8-7.4) mmol/L; prehospital arterial systolic blood pressure was less than 90 mm Hg in 179 of 324 patients (59%), 233 patients (73%) were men, and 226 (69%) required expedient hemorrhage control. There was no statistically or clinically significant between-group difference in median (IQR) total 24-hour blood product consumption (12 [5-19] U in the 4F-PCC group vs 11 [6-19] U in the placebo group; absolute difference, 0.2 U [95% CI, -2.99 to 3.33]; P\u2009=\u2009.72). In the 4F-PCC group, 56 patients (35%) presented with at least 1 thromboembolic event vs 37 patients (24%) in the placebo group (absolute difference, 11% [95% CI, 1%-21%]; relative risk, 1.48 [95% CI, 1.04-2.10]; P\u2009=\u2009.03).",
    "title": "Efficacy and Safety of Early Administration of 4-Factor Prothrombin Complex Concentrate in Patients With Trauma at Risk of Massive Transfusion: The PROCOAG Randomized Clinical Trial.",
    "xml": "<Element 'PubmedArticle' at 0x788503898360>"
}