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All About Bleeding

Acquired Bleeding Literature

F1000 Medical Research Posters

View information presented at scientific symposia.
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Perioperative Bleeding Symposia Newsletters

View expert opinions on the latest developments in haemostasis, anaesthesiology, emergency medicine, surgery, trauma and intensive care medicine from CSL Behring-sponsored satellite symposia.

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Presented here are clinical articles of interest to healthcare professionals in the areas of warfarin reversal, management of perioperative bleeding, and new oral anticoagulant reversal.

Warfarin Reversal

Prothrombin complex concentrates versus fresh frozen plasma for warfarin reversal. A systematic review and meta-analysis. (Thrombosis and Haemostasis)

Chai-Adisaksopha C, Hillis C, Siegal DM, Movilla R, Heddle N, Iorio, Crowther M. Thromb Haemost. 2016 Oct 28;116(5):879-890. Epub 2016 Aug 4.
Conclusion: As compared to FFP, the use of PCC for warfarin reversal was associated with a significant reduction in all-cause mortality, more rapid INR reduction, and less volume overload without an increased risk of thromboembolic events.
Available on Pubmed.

Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial. (Lancet)

Goldstein JN, Refaai MA, Milling TJ Jr, et al. Lancet. 2015 Feb 26. pii: S0140-6736(14)61685-8. doi: 10.1016/S0140-6736(14)61685-8. [Epub ahead of print]
Background: Rapid reversal of vitamin K antagonist (VKA)-induced anticoagulation is often necessary for patients needing urgent surgical or invasive procedures. The optimum means of VKA reversal has not been established in comparative clinical trials. We compared the efficacy and safety of four-factor prothrombin complex concentrate (4F-PCC) with that of plasma in VKA-treated patients needing urgent surgical or invasive procedures.
Available on The Lancet.

Increased risk of volume overload with plasma compared with four-factor prothrombin complex concentrate for urgent vitamin K antagonist reversal
Refaai MA, Goldstein JN, Lee ML, Durn BL, Milling TJ Jr, Sarode R. 2015 Nov;55(11):2722-9. doi: 10.1111/trf.13191. Epub 2015 Jul 1. Available on Wiley Online Library.

Thromboembolic Events After Vitamin K Antagonist Reversal With 4-Factor Prothrombin Complex Concentrate: Exploratory Analyses of Two Randomized, Plasma-Controlled Studies
Milling TJ Jr, et al. Ann Emerg Med. 2015 Jun 17. pii: S0196-0644(15)00387-X. doi: 10.1016/j.annemergmed.2015.04.036. [Epub ahead of print]. Available on ScienceDirect.

Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding. A randomized, plasma-controlled, phase IIIb study
Sarode R, Milling Jr T, Refaai M, et al. 2013;128:1234-1243. Available on American Heart Association Circulation.

Guideline on the management of bleeding in patients on antithrombotic agents
Makris M, Van Veen J, Tait C, Mumford A, Laffan M. Br J Haematol. 2013 Jan; 160(1):35-46. doi:10.1111/bjh.12107 Available on Wiley Online Library.

Factors associated with failure to correct the international normalised ratio following fresh frozen plasma administration among patients treated for warfarin-related major bleeding. An analysis of electronic health records
Menzin J, White L, Friedman M, et al. Thromb Haemost. 2012 Apr;107(4):662-72. doi: 10.1160/TH11-09-0646. Epub 2012 Feb 8. Available on Pubmed.

Failure to correct International Normalized Ratio and mortality among patients with warfarin-related major bleeding: an analysis of electronic health records
Menzin J, Hoesche J, Friedman M, et al. J Thromb Haemost. 2012 Apr;10(4):596-605. doi: 10.1111/j.1538-7836.2012.04636.x. Available on Pubmed.

Long-term safety and efficacy of a pasteurized nanofiltrated prothrombin complex concentrate (Beriplex P/N): a pharmacovigilance study
Hanke AA, Joch C, Görlinger K. Br J Anaesth. 2013 May;110(5):764-72. doi: 10.1093/bja/aes501. Epub 2013 Jan 18. Available on Pubmed.

Successful emergency reversal of phenprocoumon anticoagulation with prothrombin complex concentrate: a prospective clinical study
Lorenz R, Kienast J, Otto U, et al. Blood Coagul Fibrinolysis. 2007 Sep;18(6):565-70. Available on Pubmed.

Prothrombin complex concentrate (Beriplex® P/N) for emergency anticoagulation reversal: a prospective multinational clinical trial
Pabinger I, Brenner B, Kalina U, et. al. J Thromb Haemost. 2008 Apr;6(4):622-31. doi: 10.1111/j.1538-7836.2008.02904.x. Epub 2008 Jan 15. Available on Pubmed.

Management of Perioperative Bleeding

Introduction of an algorithm for ROTEM-guided fibrinogen concentrate administration in major obstetric haemorrhage
Mallaiah S, Barclay P, Harrod I, Chevannes C, Bhalla A. Anaesthesia. 2014 Oct 7. doi: 10.1111/anae.12859. Available on Pubmed.

Prothrombin complex concentrate (Beriplex P/N) for control of bleeding after kidney trauma in a rabbit dilutional coagulopathy model
Pragst I, Kaspereit F, Dörr B, Dickneite G. Thromb Res. 2010 Mar;125(3):272-7. doi: 10.1016/j.thromres.2009.10.011. Epub 2009 Nov 14. Available on Pubmed.

Effects of fibrinogen concentrate as first-line therapy during major aortic replacement surgery: a randomized, placebo-controlled trial
Rahe-Meyer N, Solomon, C, Hanke A, et al. Anesthesiology. 2013 Jan;118(1):40-50. doi: 10.1097/ALN.0b013e3182715d4d. Available on Pubmed.

The exclusive use of coagulation factor concentrates enables reversal of coagulopathy and decreases transfusion rates in patients with major blunt trauma
Innerhofer P, Westermann I, Tauber H, et al. Injury. 2013 Feb; 44(2):209–216. Available on ScienceDirect.

Point-of-care testing: a prospective, randomized clinical trial of efficacy in coagulopathic cardiac surgery patients
Weber CF, Görlinger K, Meininger D, et al. Anesthesiology. 2012 Sep;117(3):531-47. Available on Pubmed.

Clinical effectiveness of fresh frozen plasma compared with fibrinogen concentrate: a systematic review
Kozek-Langenecker S, Sørensen B, Hess JR, Spahn DR. Crit Care. 2011;15(5):R239. doi: 10.1186/cc10488. Epub 2011 Oct 14. Available on Pubmed.

Fibrinogen and hemostasis: a primary hemostatic target for the management of acquired bleeding
Levy JH, Szlam F, Tanaka KA, Sniecienski RM. Anesth Analg. 2012 Feb;114(2):261-74. doi: 10.1213/ANE.0b013e31822e1853. Epub 2011 Sep 29. Available on Pubmed.

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
Görlinger K, Dirkmann D, Hanke AA, et al. Anesthesiology. 2011 Dec;115(6):1179-91. doi: 10.1097/ALN.0b013e31823497dd. Available on Pubmed.

Replacement of massive blood loss
Hippala S. Vox Sang. 1998;74 Suppl 2:399-407. Available on Pubmed.

Goal-directed coagulation management of major trauma patients using rotation thromboelastometry (ROTEM)-guided administration of fibrinogen concentrate and prothrombin complex concentrate
Schöchl H, Nienaber U, Hofer G, et al. Crit Care. 2010; 14(2): R55. doi: 10.1186/cc8948 Available on Pubmed.

Reversal of New Oral Anticoagulants

Reversing the new oral anticoagulants with prothrombin complex concentrates (PCCs): what is the evidence?
Dickneite G, Hoffman M. Thromb Haemost 2014; 111: doi:10.1160/TH13-05-0431 Available on Pubmed.

Reversal of apixaban induced alterations in hemostasis by different coagulation factor concentrates: significance of studies in vitro with circulating human blood
Escolar G, Fernandez-Gallego V, Arellano-Rodrigo E, et al. PLoS ONE 8(11): e78696. doi:10.1371/journal.pone.0078696. Available on Pubmed.

Reversal of dabigatran anticoagulation by prothrombin complex concentrate (Beriplex P/N) in a rabbit model
Pragst I, Zeitler SH, Doerr B, et al. J Thromb Haemost. 2012 Sep;10(9):1841-8. doi: 10.1111/j.1538-7836.2012.04859.x. Available on Pubmed.

Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects
Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M. Circulation. 2011 Oct 4;124(14):1573-9. doi: 10.1161/CIRCULATIONAHA.111.029017. Epub 2011 Sep 6. Available on Pubmed.

Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers
Marlu R, Hodaj E, Paris A, Albaladejo P, Cracowski JL, Pernod G. Thromb Haemost. 2012 Aug;108(2):217-24. doi: 10.1160/TH12-03-0179. Epub 2012 May 25. Available on Pubmed.

Management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor-Xa inhibitors: Proposals of the Working Group on Perioperative Haemostasis (GIHP) — March 2013
Pernod G, Albaladejo P, Godier A, Samama CM, Susen S, Gruel Y, et al. Arch Cardiovasc Dis. 2013 Jun-Jul;106(6-7):382-93. doi: 10.1016/j.acvd.2013.04.009. Epub 2013 Jun 25. Available on Pubmed.

Last Updated: 12/13/2016 1:17 PM
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