Heart, Lung and Circulation

Immediate Higher-Dose Prothrombin Complex Concentrate Without Fresh Frozen Plasma or Fibrinogen Concentrate for Significant Coagulopathic Cardiac Surgical Field Bleeding


      Treatment of significant coagulopathic cardiac surgical field bleeding with immediate higher-dose prothrombin complex concentrate (PCC) without fresh frozen plasma (FFP) or fibrinogen concentrate is unexplored.


      To study characteristics, chest drainage, and clinical outcomes of patients with significant coagulopathic surgical field bleeding treated with immediate higher-dose (defined at >15 IU/kg based on factor IX) PCC without FFP or fibrinogen concentrate.


      We screened sequential cardiac surgery patients. We reviewed electronic blood bank data, Australian Society of Cardiothoracic Surgery database information and anaesthetic, intensive care unit (ICU), ward and radiological charts and electronic data. We identified patients deemed by the operating surgeon to require treatment for significant coagulopathic surgical field bleeding who underwent immediate higher-dose PCC without FFP or fibrinogen concentrate.


      Among 168 patients, we identified 30 who underwent immediate higher-dose PCC without FFP or fibrinogen concentrate. Median age was 68 years, 23 were male, 17 underwent coronary artery bypass surgery and three underwent complex surgery (David procedure, redo mitral valve surgery, and redo thoraco-abdominal aneurysm repair). Median dose of PCC was 2,500 IU. In addition, 27% underwent platelets and one underwent cryoprecipitate. Chest drainage at 24 hours was 505 ml. Survival to hospital discharge was 100%. There were no cases of pulmonary embolism, stroke, or other thrombotic events. Stage 1 AKI occurred in one patient.


      In a pilot cohort of patients with significant coagulopathic surgical field bleeding, immediate higher-dose PCC without FFP or fibrinogen concentrate was feasible and had an acceptable efficacy and safety profile, which justifies future controlled studies.


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        • Al-Attar N.
        • Johnston S.
        • Jamous N.
        • Mistry S.
        • Ghosh E.
        • Gangoli G.
        • et al.
        Impact of bleeding complications on length of stay and critical care utilization in cardiac surgery patients in England.
        J Cardiothorac Surg. 2019; 14: 64
        • Achneck H.E.
        • Sileshi B.
        • Parikh A.
        • Milano C.
        • Welsby I.
        • Lawson J.
        Pathophysiology of bleeding and clotting in the cardiac surgery patient: from vascular endothelium to circulatory assist device surface.
        Circulation. 2010; 122: 2068-2077
        • Hofer J.
        • Fries D.
        • Solomon C.
        • Velik-Salchner C.
        • Ausserer J.
        A snapshot of coagulopathy after cardiopulmonary bypass.
        Clin Appl Thromb Hemost. 2016; 22: 505-511
        • Murphy G.J.
        • Reeves B.
        • Rogers C.
        • Rizvi S.
        • Culliford L.
        • Angelini G.
        Increased mortality, postoperative morbidity, and cost after red blood cell transfusion in patients having cardiac surgery.
        Circulation. 2007; 116: 2544-2552
        • Thomas D.
        • Wee M.
        • Clyburn P.
        • Walker I.
        • Brohi K.
        • Collins P.
        • et al.
        for Association of Anaesthetists of Great Britain. Blood transfusion and the anaesthetist: management of massive haemorrhage.
        Anaesthesia. 2010; 65: 1153-1161
        • Hunt B.J.
        • Allard S.
        • Keeling D.
        • Norfolk D.
        • Stanworth S.
        • Pendry K.
        A practical guideline for the haematological management of major haemorrhage.
        Br J Haematol. 2015; 170: 788-803
        • Raphael J.
        • Mazer C.
        • Subramani S.
        • Schroeder A.
        • Abdalla M.
        • Ferreira R.
        • et al.
        Society of Cardiovascular Anesthesiologists Clinical Practice Improvement Advisory for Management of Perioperative Bleeding and Hemostasis in Cardiac Surgery Patients.
        Anesth Analg. 2019; 129: 1209-1221
        • O'Carroll-Kuehn B.U.
        • Meeran H.
        Management of coagulation during cardiopulmonary bypass.
        Continuing Edu in Anesth, Crit Care and Pain. 2007; 7: 195-198
        • Roman M.
        • Biancari F.
        • Ahmed A.
        • Agarwal S.
        • Hadjinikolaou L.
        • Al-Sarraf A.
        • et al.
        Prothrombin complex concentrate in cardiac surgery: a systematic review and meta-analysis.
        Ann Thorac Surg. 2019; 107: 1275-1283
        • Sarode R.
        • Milling T.
        • Refaai M.
        • Mangione A.
        • Schneider A.
        • Durn B.
        • et al.
        Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study.
        Circulation. 2013; 128: 1234-1243
        • Demeyere R.
        • Gillardin S.
        • Arnout J.
        • Strengers P.
        Comparison of fresh frozen plasma and prothrombin complex concentrate for the reversal of oral anticoagulants in patients undergoing cardiopulmonary bypass surgery: a randomized study.
        Vox Sang. 2010; 99: 251-260
        • Fraser T.A.
        • Corke C.F.
        • Mohajeri M.
        • Stevenson L.
        • Campbell P.J.
        A retrospective audit of the use of Prothrombinex-HT for refractory bleeding following adult cardiac surgery.
        Crit Care Resusc. 2006; 8: 141-145
        • Green L.
        • Roberts N.
        • Platton S.
        • O’Brien B.
        • Agarwal S.
        • Gill R.
        • et al.
        Impact of prothrombin complex concentrate and fresh frozen plasma on correction of haemostatic abnormalities in bleeding patients undergoing cardiac surgery (PROPHESY trial results).
        Anaesthesia. 2021; 76: 997-1000
        • Ghadimi K.
        • Levy J.H.
        • Welsby I.J.
        Prothrombin complex concentrates for bleeding in the perioperative setting.
        Anesth Analg. 2016; 122: 1287-1300
        • Gorlinger K.
        • Dirkmann D.
        • Hanke A.
        • Kamler M.
        • Kottenberg E.
        • Thielmann M.
        • et al.
        First-line therapy with coagulation factor concentrates combined with point-of-care coagulation testing is associated with decreased allogeneic blood transfusion in cardiovascular surgery: a retrospective, single-center cohort study.
        Anesthesiology. 2011; 115: 1179-1191
        • Percy C.L.
        • Hartmann R.
        • Jones R.
        • Balachandran S.
        • Mehta D.
        • Dockal M.
        • et al.
        Correcting thrombin generation ex vivo using different haemostatic agents following cardiac surgery requiring the use of cardiopulmonary bypass.
        Blood Coagul Fibrinolysis. 2015; 26: 357-367
        • Pagano D.
        • Milojevic M.
        • Meesters M.
        • Benedetto U.
        • Bolliger D.
        • von Heymann C.
        • et al.
        2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery.
        Eur J Cardiothorac Surg. 2018; 53: 79-111
        • Arnékian V.
        • Camous J.
        • Fattal S.
        • Rezaiguia-Delclaux S.
        • Nottin R.
        • Stephan F.
        Use of prothrombin complex concentrate for excessive bleeding after cardiac surgery.
        Interactive Cardiovasc and Thorac Surg. 2012; 15: 382-389
        • Cappabianca G.
        • Mariscalco G.
        • Biancari F.
        • Maselli D.
        • Papesso F.
        • Cottini M.
        • et al.
        Safety and efficacy of prothrombin complex concentrate as first-line treatment in bleeding after cardiac surgery.
        Crit Care. 2016; 20: 5
        • Fitzgerald J.
        • Lenihan M.
        • Callum J.
        • McCluskey S.A.
        • Srinivas C.
        • van Rensburg A.
        • et al.
        Use of prothrombin complex concentrate for management of coagulopathy after cardiac surgery: a propensity score matched comparison to plasma.
        Br J Anaesth. 2018; 120: 928-934
        • Song H.K.
        • Tibayan F.A.
        • Kahl E.A.
        • Sera V.A.
        • Slater M.S.
        • Deloughery T.G.
        • et al.
        Safety and efficacy of prothrombin complex concentrates for the treatment of coagulopathy after cardiac surgery.
        J Thorac Cardiovasc Surg. 2014; 147: 1036-1040
        • Kozek-Langenecker S.A.
        • Ahmed A.B.
        • Afshari A.
        • Albaladejo P.
        • Aldecoa C.
        • Barauskas G.
        • et al.
        Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology: First update 2016.
        Eur J Anaesthesiol. 2017; 34: 332-395
        • Joseph R.
        • Burner J.
        • Yates S.
        • Strickland A.
        • Tharpe W.
        • Sarode R.
        Thromboembolic outcomes after use of a four-factor prothrombin complex concentrate for vitamin K antagonist reversal in a real-world setting.
        Transfusion. 2016; 56: 799-807
        • Harper P.C.
        • Smith M.M.
        • Brinkman N.J.
        • Passe M.A.
        • Schroeder D.R.
        • Said S.M.
        • et al.
        Outcomes following three-factor inactive prothrombin complex concentrate versus recombinant activated factor VII administration during cardiac surgery.
        J Cardiothorac Vasc Anesth. 2018; 32: 151-157
      1. What Blood Products are Supplied - National Product Price List | National Blood Authority [Internet]. 2022 [cited 30 March 2022].
        (Available from)
        • Callum J.
        • Farkouh M.E.
        • Scales D.C.
        • Heddle N.M.
        • Crowther M.
        • Rao V.
        • et al.
        Effect of fibrinogen concentrate vs cryoprecipitate on blood component transfusion after cardiac surgery: the FIBRES randomized clinical trial.
        JAMA. 2019; 26: 1966-1976