Prevention and treatment of major blood loss.

The most common medical cause of major blood loss is surgery, particularly cardiovascular procedures, liver transplantation and hepatic resection, and major orthopedic procedures. Excessive blood loss may also occur for other reasons, such as trauma. This article reviews the benefits of hemostatic drugs and considers the associated risk of adverse events, particularly thrombotic complications.

[1]  S. Jones,et al.  PARVOVIRUS INFECTIONS AND HYPOPLASTIC CRISIS IN SICKLE-CELL ANAEMIA , 1981, The Lancet.

[2]  U. Pendurthi,et al.  Activity and regulation of factor VIIa analogs with increased potency at the endothelial cell surface , 2007, Journal of thrombosis and haemostasis : JTH.

[3]  R. Rossaint,et al.  Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double-blind clinical trials. , 2005, The Journal of trauma.

[4]  P. Mannucci,et al.  The Effect of Desmopressin on Reducing Blood Loss in Cardiac Surgery – A Meta-Analysis of Double-Blind, Placebo-Controlled Trials , 1995, Thrombosis and Haemostasis.

[5]  B. Boland,et al.  Recombinant Human Coagulation Factor VIIa in Jehovah's Witness Patients Undergoing Liver Transplantation , 2005, The American surgeon.

[6]  Peggy Hollingsworth-Fridlund,et al.  Original Scientific ArticlesLethal Injuries and Time to Death in a Level I Trauma Center 1 , 1998 .

[7]  D. Thabut,et al.  Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a randomized, double-blind trial. , 2004, Gastroenterology.

[8]  John D. Birkmeyer,et al.  Is ε-Aminocaproic Acid as Effective as Aprotinin in Reducing Bleeding With Cardiac Surgery? A Meta-Analysis , 1999 .

[9]  B. Chaitman,et al.  Analyses of coronary graft patency after aprotinin use: results from the International Multicenter Aprotinin Graft Patency Experience (IMAGE) trial. , 1998, The Journal of thoracic and cardiovascular surgery.

[10]  G. Ruvolo,et al.  Changes in coagulation patterns, blood loss and blood use after cardiopulmonary bypass: aprotinin vs tranexamic acid vs epsilon aminocaproic acid. , 1996, The Journal of cardiovascular surgery.

[11]  Evert de Jonge,et al.  Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints , 1999, The Lancet.

[12]  R. Porte,et al.  REDUCED TRANSFUSION REQUIREMENTS BY RECOMBINANT FACTOR VIIa IN ORTHOTOPIC LIVER TRANSPLANTATION: A Pilot Study , 2001, Transplantation.

[13]  J. Copeland,et al.  Aprotinin for primary coronary artery bypass grafting: a multicenter trial of three dose regimens. , 1996, The Annals of thoracic surgery.

[14]  D. O'shaughnessy,et al.  Activated recombinant factor VII after cardiopulmonary bypass reduces allogeneic transfusion in complex non-coronary cardiac surgery: randomized double-blind placebo-controlled pilot study. , 2005, British journal of anaesthesia.

[15]  J. Cort,et al.  Structure--activity relations of the fibrinolytic response to vasopressins in man. , 1978, Clinical science and molecular medicine.

[16]  J. Carroll,et al.  Prevention of bleeding after cardiopulmonary bypass with high-dose tranexamic acid. Double-blind, randomized clinical trial. , 1995, The Journal of thoracic and cardiovascular surgery.

[17]  M. Braun,et al.  Thromboembolic adverse events after use of recombinant human coagulation factor VIIa. , 2006, JAMA.

[18]  P. Mannucci,et al.  Desmopressin, Surgery and Thrombosis , 1994, Thrombosis and Haemostasis.

[19]  F. Loop,et al.  Aprotinin therapy for reoperative myocardial revascularization: a placebo-controlled study. , 1992, The Annals of thoracic surgery.

[20]  O. Erçelen,et al.  Effects of deamino-8-D-arginin vasopressin on blood loss and coagulation factors in scoliosis surgery. A double-blind randomized clinical trial. , 1999, Spine.

[21]  J. Philippe,et al.  Myocardial infarction in a patient with hemophilia treated with DDAVP. , 1988 .

[22]  J. García-Valdecasas,et al.  Efficacy and safety of repeated perioperative doses of recombinant factor VIIa in liver transplantation , 2005, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[23]  I. C. Tudor,et al.  The risk associated with aprotinin in cardiac surgery. , 2006, The New England journal of medicine.

[24]  P. D. de Groot,et al.  Inhibition of fibrinolysis by recombinant factor VIIa in plasma from patients with severe hemophilia A. , 2002, Blood.

[25]  R. Weintraub,et al.  Treatment with Desmopressin Acetate to Reduce Blood Loss after Cardiac Surgery , 1986 .

[26]  R. E. Clark,et al.  A multicenter, double-blind, placebo-controlled trial of aprotinin for reducing blood loss and the requirement for donor-blood transfusion in patients undergoing repeat coronary artery bypass grafting. , 1995, Circulation.

[27]  M. V. Van Dyck,et al.  Systematic use of aprotinin in cardiac surgery: influence on total homologous exposure and hospital cost. , 1992, Acta anaesthesiologica Belgica.

[28]  M. Cheang,et al.  SHORTENING OF BLEEDING TIME BY 1-DEAMINO-8-D-ARGININE VASOPRESSIN IN VARIOUS BLEEDING DISORDERS , 1984, The Lancet.

[29]  A. Peral,et al.  [Use of high doses of aprotinin in cardiac surgery]. , 1994, Revista espanola de anestesiologia y reanimacion.

[30]  J. Moake,et al.  Thrombosis following desmopressin for uremic bleeding , 1988, American journal of hematology.

[31]  W. Bechstein,et al.  Recombinant Coagulation Factor VIIa in Major Liver Resection: A Randomized, Placebo-controlled, Double-blind Clinical Trial , 2005, Anesthesiology.

[32]  M. Lamy,et al.  Liver transplantation in Jehovah's witnesses , 2005, Transplant international : official journal of the European Society for Organ Transplantation.

[33]  P. Mannucci,et al.  Randomized controlled trial of desmopressin plus terlipressin vs. terlipressin alone for the treatment of acute variceal hemorrhage in cirrhotic patients: A multicenter, double‐blind study , 1993 .

[34]  Brian Hutton,et al.  Randomized controlled trials of aprotinin in cardiac surgery: could clinical equipoise have stopped the bleeding? , 2005, Clinical trials.

[35]  W. Hiatt.  Observational studies of drug safety--aprotinin and the absence of transparency. , 2006, The New England journal of medicine.

[36]  A. Hoeft,et al.  Mortality associated with aprotinin during 5 years following coronary artery bypass graft surgery. , 2007, JAMA.

[37]  D. Bainbridge,et al.  Does Off-pump Coronary Artery Bypass Reduce Mortality, Morbidity, and Resource Utilization When Compared with Conventional Coronary Artery Bypass? A Meta-analysis of Randomized Trials , 2005, Anesthesiology.

[38]  C. Tatooles,et al.  Aprotinin for coronary bypass operations: efficacy, safety, and influence on early saphenous vein graft patency. A multicenter, randomized, double-blind, placebo-controlled study. , 1994, The Journal of thoracic and cardiovascular surgery.

[39]  P. Brady,et al.  The use of ultra-low-dose aprotinin to reduce blood loss in cardiac surgery. , 1995, Journal of cardiothoracic and vascular anesthesia.

[40]  J. Sixma,et al.  DDAVP enhances platelet adherence and platelet aggregate growth on human artery subendothelium. , 1984, Blood.

[41]  D. Pateron,et al.  Early administration of terlipressin plus glyceryl trinitrate to control active upper gastrointestinal bleeding in cirrhotic patients , 1995, The Lancet.

[42]  G. Remuzzi,et al.  Deamino-8-D-arginine vasopressin shortens the bleeding time in uremia. , 1983, The New England journal of medicine.

[43]  E. Persson,et al.  Improved hemostasis with superactive analogs of factor VIIa in a mouse model of hemophilia A. , 2003, Blood.

[44]  J. Fratantoni,et al.  Fibrin sealant: summary of a conference on characteristics and clinical uses , 1995, Transfusion.

[45]  D. Düren,et al.  DESMOPRESSIN AND MYOCARDIAL INFARCTION , 1989, The Lancet.

[46]  G. Rivard,et al.  A Trial of Desmopressin to Reduce Blood Loss in Patients Undergoing Spinal Fusion for Idiopathic Scoliosis , 1992, Anesthesia and analgesia.

[47]  K. Mann,et al.  Mechanism of factor VIIa-dependent coagulation in hemophilia blood. , 2002, Blood.

[48]  T. Treasure,et al.  Resternotomy for bleeding after cardiac operation: a marker for increased morbidity and mortality. , 1995, The Annals of thoracic surgery.

[49]  S. Pugh,et al.  A comparison of the effects of tranexamic acid and low-dose aprotinin on blood loss and homologous blood usage in patients undergoing cardiac surgery. , 1995, Journal of cardiothoracic and vascular anesthesia.

[50]  W. Beattie,et al.  Aprotinin is useful as a hemostatic agent in cardiopulmonary surgery: no , 2006, Journal of thrombosis and haemostasis : JTH.

[51]  K. M. Taylor,et al.  EFFECT OF APROTININ ON NEED FOR BLOOD TRANSFUSION AFTER REPEAT OPEN-HEART SURGERY , 1987, The Lancet.

[52]  A. Laupacis,et al.  Drugs to Minimize Perioperative Blood Loss in Cardiac Surgery: Meta-Analyses Using Perioperative Blood Transfusion As the Outcome , 1997, Anesthesia and analgesia.

[53]  O. N. Okike,et al.  Reduction of bleeding after heart operations through the prophylactic use of epsilon-aminocaproic acid. , 1996, The Journal of thoracic and cardiovascular surgery.

[54]  C. Ponticelli,et al.  IMPROVEMENT IN THE HAEMOSTATIC DEFECT OF URAEMIA AFTER TREATMENT WITH RECOMBINANT HUMAN ERYTHROPOIETIN , 1987, The Lancet.

[55]  J. Horrow,et al.  The Dose-Response Relationship of Tranexamic Acid , 1995 .

[56]  P. Corso,et al.  Effect of Clopidogrel Premedication in Off-Pump Cardiac Surgery: Are We Forfeiting the Benefits of Reduced Hemorrhagic Sequelae? , 2006, Circulation.

[57]  M. Cheang,et al.  1-Desamino-8-D-arginine vasopressin (desmopressin) decreases operative blood loss in patients having Harrington rod spinal fusion surgery. A randomized, double-blinded, controlled trial. , 1987, Annals of internal medicine.

[58]  H. Huwer,et al.  Effects of high-dose aprotinin on renal function in aortocoronary bypass grafting. , 1995, The Annals of thoracic surgery.

[59]  Gili Kenet,et al.  Treatment of traumatic bleeding with recombinant factor VIIa , 1999, The Lancet.

[60]  P. Mannucci,et al.  1-DEAMINO-8-D-ARGININE VASOPRESSIN: A NEW PHARMACOLOGICAL APPROACH TO THE MANAGEMENT OF HAEMOPHILIA AND VON WILLEBRAND'S DISEASE , 1977, The Lancet.

[61]  P. Mannucci,et al.  Multimeric composition of factor VIII/von Willebrand factor following administration of DDAVP: implications for pathophysiology and therapy of von Willebrand's disease subtypes , 1982 .

[62]  A. Alghamdi,et al.  Does the Use of Preoperative Aspirin Increase the Risk of Bleeding in Patients Undergoing Coronary Artery Bypass Grafting Surgery? Systematic Review and Meta‐Analysis , 2007, Journal of cardiac surgery.

[63]  D. Thabut,et al.  Management of acute bleeding from portal hypertension. , 2007, Best practice & research. Clinical gastroenterology.

[64]  K. Kurth,et al.  Effect of recombinant activated factor VII on perioperative blood loss in patients undergoing retropubic prostatectomy: a double-blind placebo-controlled randomised trial , 2003, The Lancet.

[65]  T. Treasure,et al.  Effect of aprotinin on clinical outcomes in coronary artery bypass graft surgery: a systematic review and meta-analysis of randomized clinical trials. , 2004, The Journal of thoracic and cardiovascular surgery.

[66]  J. Peoples,et al.  A Study of Desmopressin and Blood Loss during Spinal Fusion for Neuromuscular Scoliosis: A Randomized, Controlled, Double‐Blinded Study , 1997, Anesthesiology.

[67]  M. Franck,et al.  Consequences Hemodynamiques Maternelles d'Une CEC Foetale À Debit Pulse Vs Debit Continu , 1995 .

[68]  M. Levi,et al.  The activation of factor X and prothrombin by recombinant factor VIIa in vivo is mediated by tissue factor. , 1993, The Journal of clinical investigation.

[69]  L. Eijsman,et al.  Hemostatic efficacy of dipyridamole, tranexamic acid, and aprotinin in coronary bypass grafting. , 1995, The Annals of thoracic surgery.

[70]  E. Vamvakas,et al.  The continuing risk of transfusion-transmitted infections. , 2006, The New England journal of medicine.

[71]  R. Weiskopf.  Assessment of hemostasis through the retrospectroscope , 2006, Journal of thrombosis and haemostasis : JTH.

[72]  S. McCluskey,et al.  Recombinant factor VIIa for intractable blood loss after cardiac surgery: a propensity score–matched case‐control analysis , 2005, Transfusion.

[73]  B. Mcleod.  Myocardial infarction in a blood donor after administration of desmopressin , 1990, The Lancet.

[74]  P Hollingsworth-Fridlund,et al.  Lethal injuries and time to death in a level I trauma center. , 1998, Journal of the American College of Surgeons.

[75]  S. Bélisle,et al.  Low-dose aprotinin infusion is not clinically useful to reduce bleeding and transfusion of homologous blood products in high-risk cardiac surgical patients , 1993, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[76]  Dougald M Monroe,et al.  The use of recombinant factor VIIa in the treatment of bleeding disorders. , 2004, Blood.

[77]  J. Fontcuberta,et al.  Aprotinin versus desmopressin for patients undergoing operations with cardiopulmonary bypass. A double-blind placebo-controlled study. , 1995, The Journal of thoracic and cardiovascular surgery.

[78]  I. Ferreira-González,et al.  Outcomes in off-pump vs. on-pump coronary artery bypass grafting stratified by pre-operative risk profile: an assessment using propensity score. , 2006, European heart journal.

[79]  R. Prêtre,et al.  Influence of aprotinin on early graft thrombosis in patients undergoing myocardial revascularization. , 1994, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[80]  Keyvan Karkouti,et al.  A propensity score case‐control comparison of aprotinin and tranexamic acid in high‐transfusion‐risk cardiac surgery , 2006, Transfusion.

[81]  H. Lummis,et al.  The use of low-dose aprotinin, epsilon-aminocaproic acid or tranexamic acid for prevention of mediastinal bleeding in patients receiving aspirin before coronary artery bypass operations. , 1997, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[82]  M. Petricevic,et al.  Tranexamic acid reduces postbypass blood use: a double-blinded, prospective, randomized study of 210 patients. , 1996, The Annals of thoracic surgery.

[83]  F. Sellke,et al.  Aprotinin in cardiac surgery , 2006, Expert review of cardiovascular therapy.

[84]  C. Bailey,et al.  Randomized placebo‐controlled double‐blind study of three aprotinin regimens in primary cardiac surgery , 1994, British Journal of Surgery.

[85]  M. Ray,et al.  Preoperative platelet dysfunction increases the benefit of aprotinin in cardiopulmonary bypass. , 1997, The Annals of thoracic surgery.

[86]  T. Brott,et al.  Recombinant factor VIIa in patients with coagulopathy secondary to anticoagulant therapy, cirrhosis, or severe traumatic injury: review of safety profile , 2006, Transfusion.

[87]  T. Ortel,et al.  Heparin-induced thrombocytopenia. , 2006, Seminars in hematology.

[88]  B. Binder,et al.  Assessment of Hemostasis , 1997 .

[89]  Po-Huang Lee,et al.  Safety and hemostatic effect of recombinant activated factor VII in cirrhotic patients undergoing partial hepatectomy: a multicenter, randomized, double-blind, placebo-controlled trial. , 2006, American journal of surgery.

[90]  A. Sturk,et al.  Low-dose and high-dose aprotinin improve hemostasis in coronary operations. , 1996, The Journal of thoracic and cardiovascular surgery.

[91]  L. Salemark,et al.  A prospective double blind randomized study comparing the need for blood transfusion with terlipressin or a placebo during early excision and grafting of burns. , 2004, Burns : journal of the International Society for Burn Injuries.

[92]  P. Aebersold,et al.  Regulatory perspectives on clinical trials for trauma, transfusion, and hemostasis , 2005, Transfusion.

[93]  M. Irwin,et al.  Desmopressin does not decrease blood loss and transfusion requirements in patients undergoing hepatectomy , 2003, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[94]  C. Naylor,et al.  Metaanalysis of prophylactic drug treatment in the prevention of postoperative bleeding. , 1994, The Annals of thoracic surgery.

[95]  X. Moreau,et al.  Comparaison des effets de l’aprotinine et de l’acide tranexamique sur le saignement en chirurgie cardiaque , 1995 .

[96]  J. Levy,et al.  Aprotinin is useful as a hemostatic agent in cardiopulmonary surgery: yes , 2006, Journal of thrombosis and haemostasis : JTH.

[97]  A. Spotnitz,et al.  Hemorrhage Related Reexploration following Open Heart Surgery: The Impact of Pre-Operative and Post-Operative Coagulation Testing , 2002, Cardiovascular surgery.

[98]  L. Stitt,et al.  Does clopidogrel increase blood loss following coronary artery bypass surgery? , 2004, The Annals of thoracic surgery.

[99]  M. Schechter,et al.  A trial of desmopressin (1-desamino-8-D-arginine vasopressin) to reduce blood loss in uncomplicated cardiac surgery. , 1989, The New England journal of medicine.

[100]  S. Mayer,et al.  Recombinant Activated Factor VII for Acute Intracerebral Hemorrhage , 2007, Stroke.

[101]  H. Büller,et al.  Efficacy and safety of recombinant factor VIIa for treatment of severe bleeding: A systematic review , 2005, Critical care medicine.

[102]  D. V. Van Riper,et al.  Hemostatic Effects of Tranexamic Acid and Desmopressin During Cardiac Surgery , 1991, Circulation.

[103]  L. Cohn,et al.  Aprotinin in primary valve replacement and reconstruction: a multicenter, double-blind, placebo-controlled trial. , 1996, The Journal of thoracic and cardiovascular surgery.

[104]  P. Mannucci,et al.  Mechanism of Plasminogen Activator and Factor VIII Increase after Vasoactive Drugs , 1975, British journal of haematology.

[105]  J. Paramo,et al.  Does desmopressin acetate reduce blood loss after surgery in patients on cardiopulmonary bypass? , 1988, Circulation.

[106]  J. Forrest,et al.  Haemostatic effects of lysine vasopressin and triglycyl lysine vasopressin infusion in patients with cirrhosis , 1980, European journal of clinical investigation.