Effectiveness of prothrombin complex concentrate for the treatment of bleeding: A systematic review and meta‐analysis

Prothrombin complex concentrate (PCC) is increasingly being used as a treatment for major bleeding in patients who are not taking anticoagulants. The aim of this systematic review and meta‐analysis is to evaluate the effectiveness of PCC administration for the treatment of bleeding in patients not taking anticoagulants. Studies investigating the effectivity of PCC to treat bleeding in adult patients and providing data on either mortality or blood loss were eligible. Data were pooled using Mantel‐Haenszel random effects meta‐analysis or inverse variance random effects meta‐analysis. From 4668 identified studies, 17 observational studies were included. In all patient groups combined, PCC administration was not associated with mortality (odds ratio = 0.83; 95% confidence interval [CI], 0.66‐1.06; P = .13; I2 = 0%). However, in trauma patients, PCC administration, in addition to fresh frozen plasma, was associated with reduced mortality (odds ratio = 0.64; CI, 0.46‐0.88; P = .007; I2 = 0%). PCC administration was associated with a reduction in blood loss in cardiac surgery patients (mean difference: −384; CI, −640 to −128, P = .003, I2 = 81%) and a decreased need for red blood cell transfusions when compared with standard care across a wide range of bleeding patients not taking anticoagulants (mean difference: −1.80; CI, −3.22 to −0.38; P = .01; I2 = 92%). In conclusion, PCC administration was not associated with reduced mortality in the whole cohort but did reduce mortality in trauma patients. In bleeding patients, PCC reduced the need for red blood cell transfusions when compared with treatment strategies not involving PCC. In bleeding cardiac surgery patients, PCC administration reduced blood loss.

[1]  S. Varnado,et al.  Evaluation of postoperative clinical outcomes in Jehovah's Witness patients who receive prothrombin complex concentrate during cardiac surgery , 2020, Journal of cardiac surgery.

[2]  Ashley Northcutt,et al.  Four-factor prothrombin complex concentrate is associated with improved survival in trauma-related hemorrhage: A nationwide propensity-matched analysis , 2019, Journal of Trauma and Acute Care Surgery.

[3]  F. Biancari,et al.  Comparative Analysis of Prothrombin Complex Concentrate and Fresh Frozen Plasma in Coronary Surgery. , 2019, Heart, lung & circulation.

[4]  R. Bellomo,et al.  Initial Experience of the Use of 3-Factor Prothrombin Complex Concentrate and Thromboembolic Complications After Cardiac Surgery. , 2019, Heart, lung & circulation.

[5]  M. Zeeshan,et al.  The role of four-factor prothrombin complex concentrate in coagulopathy of trauma: A propensity matched analysis , 2018, The journal of trauma and acute care surgery.

[6]  S. McCluskey,et al.  Use of prothrombin complex concentrate for management of coagulopathy after cardiac surgery: a propensity score matched comparison to plasma , 2018, British journal of anaesthesia.

[7]  J. Smith,et al.  Current evidence of oral anticoagulant reversal: A systematic review. , 2018, Thrombosis research.

[8]  Elizabeth Mcneely,et al.  Activated Factor 7 Versus 4-Factor Prothrombin Complex Concentrate for Critical Bleeding Post–Cardiac Surgery , 2018, The Annals of pharmacotherapy.

[9]  Tiejun Tong,et al.  Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range , 2015, Statistical methods in medical research.

[10]  D. Schroeder,et al.  Outcomes Following Three-Factor Inactive Prothrombin Complex Concentrate Versus Recombinant Activated Factor VII Administration During Cardiac Surgery. , 2018, Journal of cardiothoracic and vascular anesthesia.

[11]  A. Koster,et al.  2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery. , 2018, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[12]  C. Leveque,et al.  Impact of intraoperative factor concentrates on blood product transfusions during orthotopic liver transplantation , 2017, Transfusion.

[13]  R. Porte,et al.  Pathogenesis, prevention, and management of bleeding and thrombosis in patients with liver diseases , 2017, Research and practice in thrombosis and haemostasis.

[14]  Sandeep Sharma,et al.  Retrospective analysis of post-operative coagulopathy after major hepatic resection at a tertiary care centre in Northern India , 2017, Indian journal of anaesthesia.

[15]  V. Hjortdal,et al.  Rational and timely haemostatic interventions following cardiac surgery - coagulation factor concentrates or blood bank products. , 2017, Thrombosis research.

[16]  A. Mayr,et al.  Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial. , 2017, The Lancet. Haematology.

[17]  A. Schubert,et al.  Combined effect of therapeutic strategies for bleeding injury on early survival, transfusion needs and correction of coagulopathy , 2017, The British journal of surgery.

[18]  P. Rhee,et al.  Assessing the Efficacy of Prothrombin Complex Concentrate in Multiply Injured Patients With High-Energy Pelvic and Extremity Fractures , 2016, Journal of orthopaedic trauma.

[19]  T. Deloughery,et al.  Retrospective study of rFVIIa, 4‐factor PCC, and a rFVIIa and 3‐factor PCC combination in improving bleeding outcomes in the warfarin and non‐warfarin patient , 2016, American journal of hematology.

[20]  J. Vincent,et al.  The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition , 2016, Critical Care.

[21]  F. Biancari,et al.  Safety and efficacy of prothrombin complex concentrate as first-line treatment in bleeding after cardiac surgery , 2015, Critical Care.

[22]  R. Adamson,et al.  Safety of Prothombin Complex Concentrate to Control Excess Bleeding During Continuous Flow LVAD Insertion , 2015, ASAIO journal.

[23]  M. Trivella,et al.  Fresh frozen plasma for cardiovascular surgery. , 2015, The Cochrane database of systematic reviews.

[24]  L. Sharples,et al.  An Exploratory Cohort Study Comparing Prothrombin Complex Concentrate and Fresh Frozen Plasma for the Treatment of Coagulopathy After Complex Cardiac Surgery , 2015, Anesthesia and analgesia.

[25]  David B Hoyt,et al.  Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. , 2015, JAMA.

[26]  Xian-tao Zeng,et al.  The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta‐analysis, and clinical practice guideline: a systematic review , 2015, Journal of evidence-based medicine.

[27]  Klaus Görlinger,et al.  Coagulation management with factor concentrates in liver transplantation: a single‐center experience , 2014, Transfusion.

[28]  P. Rhee,et al.  Prothrombin Complex Concentrate Versus Fresh-Frozen Plasma for Reversal of Coagulopathy of Trauma: Is There a Difference? , 2014, World Journal of Surgery.

[29]  S. Stanworth,et al.  Damage control resuscitation using blood component therapy in standard doses has a limited effect on coagulopathy during trauma hemorrhage , 2014, Intensive Care Medicine.

[30]  M. Mazzeffi,et al.  Three‐factor prothrombin complex concentrate and hemostasis after high‐risk cardiovascular surgery , 2013, Transfusion.

[31]  P. Innerhofer,et al.  The exclusive use of coagulation factor concentrates enables reversal of coagulopathy and decreases transfusion rates in patients with major blunt trauma. , 2013, Injury.

[32]  C. Joch,et al.  Long-term safety and efficacy of a pasteurized nanofiltrated prothrombin complex concentrate (Beriplex P/N): a pharmacovigilance study , 2013, British Journal of Anaesthesia.

[33]  L. Cohn,et al.  Point-of-Care Testing: A Prospective, Randomized Clinical Trial of Efficacy in Coagulopathic Cardiac Surgery Patients , 2012, Anesthesiology.

[34]  Suchitra Pandey,et al.  Adverse effects of plasma transfusion , 2012, Transfusion.

[35]  A. Hanke,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. , 2011, Anesthesiology.

[36]  R. Attal,et al.  The impact of fresh frozen plasma vs coagulation factor concentrates on morbidity and mortality in trauma-associated haemorrhage and massive transfusion. , 2011, Injury.

[37]  Ognjen Gajic,et al.  Incidence and transfusion risk factors for transfusion‐associated circulatory overload among medical intensive care unit patients , 2011, Transfusion.

[38]  D. Reich,et al.  Risk Factors for Intraoperative Coagulopathy in Cardiac Surgery , 2010 .

[39]  G. Lippi,et al.  Prothrombin complex concentrates: an update. , 2010, Blood transfusion = Trasfusione del sangue.

[40]  W. Voelckel,et al.  Goal-directed coagulation management of major trauma patients using thromboelastometry (ROTEM®)-guided administration of fibrinogen concentrate and prothrombin complex concentrate , 2010, Critical care.

[41]  W. Voelckel,et al.  Use of rotation thromboelastometry (ROTEM®) to achieve successful treatment of polytrauma with fibrinogen concentrate and prothrombin complex concentrate , 2010, Anaesthesia.

[42]  D. Moher,et al.  Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement , 2009, BMJ : British Medical Journal.

[43]  R. Lefering,et al.  Early coagulopathy in multiple injury: an analysis from the German Trauma Registry on 8724 patients. , 2007, Injury.

[44]  Mauricio Lynn,et al.  Early coagulopathy predicts mortality in trauma. , 2003, The Journal of trauma.

[45]  Karim Brohi,et al.  Acute traumatic coagulopathy. , 2003, The Journal of trauma.