Pharmacologic tools to reduce bleeding in surgery.

Strategies to reduce blood loss and the need for transfusions in surgery include enhancement of coagulation, inhibition of fibrinolysis, and an improved decision algorithm for transfusion based on bedside monitoring of global hemostasis. The synthetic antifibrinolytic drug tranexamic acid has emerged as an effective alternative in this respect for orthopedic and cardiac surgery. Although it seems less effective than aprotinin, it has not been associated with the increased risk of mortality of the latter. Thromboelastography to monitor the global hemostatic capacity and to guide the appropriate use of blood components in cardiac surgery is also effective in reducing the need for transfusion. Patients on antithrombotic drug therapy may need reversal before surgery to avoid excessive blood loss, or intraoperatively in cases of unexpected bleeding. Available options are protamine for unfractionated or low-molecular-weight heparin, recombinant activated factor VII for fondaparinux, prothrombin complex concentrate for vitamin K antagonists and possibly for oral factor Xa inhibitors, dialysis and possibly activated prothrombin complex concentrate for oral thrombin inhibitors, desmopressin for aspirin and possibly for thienopyridines, and platelet transfusions for the latter.

[1]  T. Ortel Perioperative management of patients on chronic antithrombotic therapy. , 2012, Hematology. American Society of Hematology. Education Program.

[2]  S. Connolly,et al.  Recombinant factor VIIa (rFVIIa) and hemodialysis to manage massive dabigatran-associated postcardiac surgery bleeding. , 2012, Blood.

[3]  S. Schulman,et al.  Thromboembolic safety and efficacy of prothrombin complex concentrates in the emergency reversal of warfarin coagulopathy. , 2012, Thrombosis research.

[4]  A. Nargol,et al.  Tranexamic acid in total knee replacement: a systematic review and meta-analysis. , 2011, The Journal of bone and joint surgery. British volume.

[5]  P. Kamphuisen,et al.  Reversal of Rivaroxaban and Dabigatran by Prothrombin Complex Concentrate: A Randomized, Placebo-Controlled, Crossover Study in Healthy Subjects , 2011, Circulation.

[6]  P. Kamphuisen,et al.  Bleeding risk and reversal strategies for old and new anticoagulants and antiplatelet agents , 2011, Journal of thrombosis and haemostasis : JTH.

[7]  W. Ageno,et al.  Safety of prothrombin complex concentrates for rapid anticoagulation reversal of vitamin K antagonists , 2011, Thrombosis and Haemostasis.

[8]  Jean A. Orman,et al.  Tranexamic acid for trauma patients: a critical review of the literature. , 2011, The Journal of trauma.

[9]  K. Ker,et al.  Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. , 2011, The Cochrane database of systematic reviews.

[10]  J. Nawarskas,et al.  Ticagrelor: a novel reversible oral antiplatelet agent. , 2011, Cardiology in review.

[11]  C. Long,et al.  Perioperative monitoring of thromboelastograph on blood protection and recovery for severely cyanotic patients undergoing complex cardiac surgery. , 2010, Artificial organs.

[12]  K. Rathgen,et al.  Influence of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Oral Dabigatran Etexilate , 2010, Clinical pharmacokinetics.

[13]  R. Salamonsen,et al.  Protocol based on thromboelastograph (TEG) out-performs physician preference using laboratory coagulation tests to guide blood replacement during and after cardiac surgery: a pilot study. , 2009, Heart, lung & circulation.

[14]  A. Civelek,et al.  Thromboelastography‐Based Transfusion Algorithm Reduces Blood Product Use after Elective CABG: A Prospective Randomized Study , 2009, Journal of cardiac surgery.

[15]  S. Skrtic,et al.  Prophylactic fibrinogen infusion reduces bleeding after coronary artery bypass surgery , 2009, Thrombosis and Haemostasis.

[16]  J. Douketis,et al.  Use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopedic surgery: a systematic review of randomized trials. , 2009, Thrombosis research.

[17]  A. Laupacis,et al.  The safety of aprotinin and lysine-derived antifibrinolytic drugs in cardiac surgery: a meta-analysis , 2009, Canadian Medical Association Journal.

[18]  Du Feng,et al.  The use of antifibrinolytic agents in spine surgery. A meta-analysis. , 2008, The Journal of bone and joint surgery. American volume.

[19]  R. Martineau,et al.  A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. , 2008, The New England journal of medicine.

[20]  G. Hicks,et al.  Increased risk of infection and mortality in women after cardiac surgery related to allogeneic blood transfusion. , 2007, Journal of women's health.

[21]  J. Gill,et al.  The use of antifibrinolytic agents in total hip arthroplasty: a meta-analysis. , 2006, The Journal of arthroplasty.

[22]  S. Yusuf,et al.  Adverse Impact of Bleeding on Prognosis in Patients With Acute Coronary Syndromes , 2006, Circulation.

[23]  Lorne L Holland,et al.  Toward rational fresh frozen plasma transfusion: The effect of plasma transfusion on coagulation test results. , 2006, American journal of clinical pathology.

[24]  Lorne L Holland,et al.  Toward Rational Fresh Frozen Plasma Transfusion , 2006 .

[25]  M. Avidan,et al.  Comparison of structured use of routine laboratory tests or near-patient assessment with clinical judgement in the management of bleeding after cardiac surgery. , 2004, British journal of anaesthesia.

[26]  A. Laupacis,et al.  Desmopressin for minimising perioperative allogeneic blood transfusion. , 2004, The Cochrane database of systematic reviews.

[27]  P. D. de Groot,et al.  Recombinant factor VIIa reverses the in vitro and ex vivo anticoagulant and profibrinolytic effects of fondaparinux , 2003, Journal of thrombosis and haemostasis : JTH.

[28]  R. Peters,et al.  Ability of Recombinant Factor VIIa to Reverse the Anticoagulant Effect of the Pentasaccharide Fondaparinux in Healthy Volunteers , 2002, Circulation.

[29]  S. Ishii,et al.  Timing of the administration of tranexamic acid for maximum reduction in blood loss in arthroplasty of the knee. , 2001, The Journal of bone and joint surgery. British volume.

[30]  S. Carlsson,et al.  Effect of activated prothrombin complex concentrate or recombinant factor VIIa on the bleeding time and thrombus formation during anticoagulation with a direct thrombin inhibitor. , 2001, Thrombosis research.

[31]  M. DePerio,et al.  Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery. , 1999, Anesthesia and analgesia.

[32]  Ong,et al.  Menorrhagia in von Willebrand disease successfully treated with single daily dose tranexamic acid , 1998, Haemophilia : the official journal of the World Federation of Hemophilia.

[33]  P. Mannucci,et al.  Fibrinolytic shut‐down after surgery: impairment of the balance between tissue‐type plasminogen activator and its specific inhibitor , 1985, European journal of clinical investigation.

[34]  R. Stafford,et al.  Safety of recombinant activated factor VII in randomized clinical trials. , 2011, The New England journal of medicine.

[35]  S. Molliex,et al.  Tranexamic acid in hip fracture surgery: a randomized controlled trial. , 2010, British journal of anaesthesia.

[36]  B. Leithäuser,et al.  Effects of desmopressin on platelet membrane glycoproteins and platelet aggregation in volunteers on clopidogrel. , 2008, Clinical hemorheology and microcirculation.

[37]  S. Schulman,et al.  Anticoagulants and their reversal. , 2007, Transfusion medicine reviews.

[38]  A. Laupacis,et al.  Desmopressin for minimising perioperative allogeneic blood transfusion. , 2004, The Cochrane database of systematic reviews.