BACKGROUND: Single-dose human fibrinogen concentrate (FCH) might have haemostatic benefits in complex cardiovascular surgery. METHODS: Patients undergoing elective aortic surgery requiring cardiopulmonary bypass were randomly assigned to receive FCH or placebo. Study medication was administered to patients with a 5 min bleeding mass of 60-250 g after separation from bypass and surgical haemostasis. A standardized algorithm for allogeneic blood product transfusion was followed if bleeding continued after study medication. RESULTS: 519 patients from 34 centres were randomized, of whom 152 (29%) met inclusion criteria for study medication. Median (IQR) pretreatment 5 min bleeding mass was 107 (76-138) and 91 (71-112) g in the FCH and placebo groups, respectively (P=0.13). More allogeneic blood product units were administered during the first 24 h after FCH, 5.0 (2.0-11.0), when compared with placebo, 3.0 (0.0-7.0), P=0.026. Fewer patients avoided transfusion in the FCH group (15.4%) compared with placebo (28.4%), P=0.047. The FCH immediately increased plasma fibrinogen concentration and fibrin-based clot strength. Adverse event rates were comparable in each group. CONCLUSIONS: Human fibrinogen concentrate was associated with increased allogeneic blood product transfusion, an unexpected finding contrary to previous studies. Human fibrinogen concentrate may not be effective in this setting when administered according to 5-minute bleeding mass. Low bleeding rates and normal-range plasma fibrinogen concentrations before study medication, and variability in adherence to the complex transfusion algorithm, may have contributed to these results. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier no. NCT01475669; EudraCT trial no. 2011-002685-20.

Clinic for Anesthesiology and Intensive Care Medicine Franziskus Hospital Kiskerstraße 26 D 33615 Bielefeld Germany

CSL Behring King of Prussia PA USA

CSL Behring Marburg Germany

Duke University School of Medicine Durham NC USA

Faculty of Medicine University of Ostrava Ostrava Czech Republic

Helsinki University Hospital Helsinki Finland

Kobe University Hospital Kobe Japan

Nagoya University Graduate School of Medicine Nagoya Japan

Papworth Hospital Cambridge UK

St Michael's Hospital University of Toronto Toronto ON Canada

University Hospital of Southampton Southampton UK

Br J Anaesth. 2018 Feb;120(2):407-409. doi: 10.1016/j.bja.2017.11.092. PubMed

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Sniecinski RM, Levy JH. Bleeding and management of coagulopathy. J Thorac Cardiovasc Surg 2011; 142: 662–7 PubMed

Nascimento B, Goodnough LT, Levy JH. Cryoprecipitate therapy. Br J Anaesth 2014; 113: 922–34 PubMed PMC

Pandey S, Vyas GN. Adverse effects of plasma transfusion. Transfusion 2012; 52(Suppl 1): 65S–79S PubMed PMC

Levy JH, Szlam F, Tanaka KA, Sniecienski RM. Fibrinogen and hemostasis: a primary hemostatic target for the management of acquired bleeding. Anesth Analg 2012; 114: 261–74 PubMed

Tanaka KA, Esper S, Bolliger D. Perioperative factor concentrate therapy. Br J Anaesth 2013; 111(Suppl 1): i35–49 PubMed

Solomon C, Rahe-Meyer N, Sørensen B. Fibrin formation is more impaired than thrombin generation and platelets immediately following cardiac surgery. Thromb Res 2011; 128: 277–82 PubMed

Hiippala ST, Myllylä GJ, Vahtera EM. Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates. Anesth Analg 1995; 81: 360–5 PubMed

Gielen C, Dekkers O, Stijnen T et al. . The effects of pre- and postoperative fibrinogen levels on blood loss after cardiac surgery: a systematic review and meta-analysis. Interact Cardiovasc Thorac Surg 2014; 18: 292–8 PubMed PMC

Karlsson M, Ternström L, Hyllner M, Baghaei F, Nilsson S, Jeppsson A. Plasma fibrinogen level, bleeding, and transfusion after on-pump coronary artery bypass grafting surgery: a prospective observational study. Transfusion 2008; 48: 2152–8 PubMed

Reinhöfer M, Brauer M, Franke U, Barz D, Marx G, Lösche W. The value of rotation thromboelastometry to monitor disturbed perioperative haemostasis and bleeding risk in patients with cardiopulmonary bypass. Blood Coagul Fibrinolysis 2008; 19: 212–9 PubMed

Levy JH, Welsby I, Goodnough LT. Fibrinogen as a therapeutic target for bleeding: a review of critical levels and replacement therapy. Transfusion 2014; 54: 1389–405 PubMed

Costa-Filho R, Hochleitner G, Wendt M, Teruya A, Spahn DR. Over 50 years of fibrinogen concentrate. Clin Appl Thromb Hemost 2016; 22: 109–14 PubMed PMC

Solomon C, Pichlmaier U, Schoechl H et al. . Recovery of fibrinogen after administration of fibrinogen concentrate to patients with severe bleeding after cardiopulmonary bypass surgery. Br J Anaesth 2010; 104: 555–62 PubMed PMC

Bolliger D, Szlam F, Molinaro RJ, Rahe-Meyer N, Levy JH, Tanaka KA. Finding the optimal concentration range for fibrinogen replacement after severe haemodilution: an in vitro model. Br J Anaesth 2009; 102: 793–9 PubMed

Rahe-Meyer N, Pichlmaier M, Haverich A et al. . Bleeding management with fibrinogen concentrate targeting a high-normal plasma fibrinogen level: a pilot study. Br J Anaesth 2009; 102: 785–92 PubMed PMC

Rahe-Meyer N, Solomon C, Winterhalter M et al. . Thromboelastometry-guided administration of fibrinogen concentrate for the treatment of excessive intraoperative bleeding in thoracoabdominal aortic aneurysm surgery. J Thorac Cardiovasc Surg 2009; 138: 694–702 PubMed

Rahe-Meyer N, Hanke A, Schmidt DS, Hagl C, Pichlmaier M. Fibrinogen concentrate reduces intraoperative bleeding when used as first-line hemostatic therapy during major aortic replacement surgery: results from a randomized, placebo-controlled trial. J Thorac Cardiovasc Surg 2013; 145: S178–85 PubMed

Rahe-Meyer N, Solomon C, Hanke A et al. . Effects of fibrinogen concentrate as first-line therapy during major aortic replacement surgery: a randomized, placebo-controlled trial. Anesthesiology 2013; 118: 40–50 PubMed

Solomon C, Schöchl H, Hanke A et al. . Haemostatic therapy in coronary artery bypass graft patients with decreased platelet function: comparison of fibrinogen concentrate with allogeneic blood products. Scand J Clin Lab Invest 2012; 72: 121–8 PubMed

Ranucci M, Baryshnikova E, Crapelli GB et al. . Randomized, double-blinded, placebo-controlled trial of fibrinogen concentrate supplementation after complex cardiac surgery. J Am Heart Assoc 2015; 4: e002066. PubMed PMC

Karlsson M, Ternström L, Hyllner M et al. . Prophylactic fibrinogen infusion reduces bleeding after coronary artery bypass surgery. A prospective randomised pilot study. Thromb Haemost 2009; 102: 137–44 PubMed

Solomon C, Gröner A, Ye J, Pendrak I. Safety of fibrinogen concentrate: analysis of more than 27 years of pharmacovigilance data. Thromb Haemost 2015; 113: 759–71 PubMed

Zobrazit více v PubMed

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NCT01475669