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Drug Safety

, Volume 31, Issue 3, pp 217–230 | Cite as

A Benefit-Risk Review of Systemic Haemostatic Agents

Part 1: In Major Surgery
  • Ian S. Fraser
  • Robert J. Porte
  • Peter A. Kouides
  • Andrea S. Lukes
Review Article

Abstract

Systemic haemostatic agents play an important role in the management of blood loss during major surgery where significant blood loss is likely and their use has increased in recent times as a consequence of demand for blood products outstripping supply and the risks associated with transfusions. Their main application is as prophylaxis to reduce bleeding in major surgery, including cardiac and orthopaedic surgery and orthotopic liver transplantation. Aprotinin has been the predominant agent used in this setting; of the other antifibrinolytic agents that have been studied, tranexamic acid is the most effective and e-aminocaproic acid may also have a role. Eptacog alfa (recombinant factor VIIa) has also shown promise. Tranexamic acid, e-aminocaproic acid and eptacog alfa are generally well tolerated; however, when considering the methods to reduce or prevent blood loss intra- and postoperatively, the benefits of these agents need to be weighed against the risk of adverse events. Recently, concerns have been raised about the safety of aprotinin after an association between increased renal dysfunction and mortality was shown in retrospective observational studies and an increase in allcause mortality with aprotinin relative to tranexamic acid or e-aminocaproic acid was seen after a pre-planned periodic analysis of the large BART (Blood conservation using Antifibrinolytics in a Randomized Trial) study. The latter finding resulted in the trial being halted, and aprotinin has subsequently been withdrawn from the market pending detailed analysis of efficacy and safety results from the study. Part 1 of this benefit-risk review examines the efficacy and adverse effect profiles of systemic haemostatic agents commonly used in surgery, and provides individual benefit-risk profiles that may assist clinicians in selecting appropriate pharmacological therapy in this setting.

Keywords

Aprotinin Orthotopic Liver Transplantation Tranexamic Acid Desmopressin Transfusion Requirement 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

Funding for the preparation of this manuscript was provided by Daiichi Sankyo Co., Ltd.

Dr Fraser has undertaken consultancies, given lectures for or received honoraria for scientific contributions to meetings for the Daiichi Sankyo, Organon and Schering companies. Dr Porte has previously received an unrestricted research grant from Bayer Pharmaceuticals and is involved in a trial that is co-sponsored by Johnson & Johnson. Dr Kouides serves on the advisory board of CSL Behring (which markets intranasal desmopressin), has been a consultant to the Ferring Pharmaceuticals (which manufactures desmopressin) and serves on the Drug Monitoring Safety Boards of Xanodyne Pharmaceuticals Inc. (which markets ε-aminocaproic acid and is developing a sustained-release form of oral tranexamic acid). Dr Lukes has been an investigator on several trials using tranexamic acid, including the CDC study on heavy periods using tranexamic acid and desmopressin, is a consultant to Xanodyne Pharmaceuticals Inc. (who are pursuing FDA approval for tranexamic acid in the US) and has been a speaker for Daiichi Sankyo Co. Ltd (FIGO 2006). Dr Lukes received a small stipend for contributing to this manuscript.

The authors would like to thank Dr Susan Keam, of Wolters Kluwer Health Medical Communications, for her assistance in the writing and editing of this manuscript.

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Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  • Ian S. Fraser
    • 1
  • Robert J. Porte
    • 2
  • Peter A. Kouides
    • 3
  • Andrea S. Lukes
    • 4
  1. 1.Department of Obstetrics and GynaecologyUniversity of SydneySydneyAustralia
  2. 2.Department of SurgeryUniversity Medical Center Groningenm University of GroningenGroningenThe Netherlands
  3. 3.Mary M. Gooely Hemophilia Center of RochesterRochesterUSA
  4. 4.Carolina Women’s Research and Wellness CenterDurhamUSA

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