Miscellaneous
In this episode of the APEX Live Anesthesia Podcast we talk clotting…or more specifically how to promote blood clotting and STOP BLEEDING by giving an antifibrinolytic. We review the mechanisms of how a clot is formed and broken down. We then discuss several large trials published within the last decade that focus on situations where antifibrinolytics may be useful. What You’ll Learn How are blood clots formed and broken down? What are the mechanisms of action of the various antifibrinolytic agents? Which antifibrinolytic agents are currently being used? What are the surgical situations where antifibrinolytics are used? What are the CRASH 2 and CRASH 3 trials? Recommended Resources Bennett C, Klingenberg SL, Langholz E, Gluud LL. Tranexamic acid for upper gastrointestinal bleeding. Cochrane Database Syst Rev. 2014;2014(11):CD006640. Published 2014 Nov 21. https://pubmed.ncbi.nlm.nih.gov/25414987/ Brenner, A., Afolabi, A., Ahmad, S.M. et al.Tranexamic acid for acute gastrointestinal bleeding (the HALT-IT trial): statistical analysis plan for an international, randomised, double-blind, placebo-controlled trial. Trials 20, 467 (2019). https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-019-3561-7 Cole, E., et al. Tranexamic Acid Use in Severely Injured Civilian Patients and the Effects on Outcomes: A Prospective Cohort Study. Annals of Surgery 2015;261(2):390. https://pubmed.ncbi.nlm.nih.gov/25412319/ Gayet-Ageron A, Prieto-Merino D, Ker K, et al. Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe haemorrhage: a meta-analysis of individual patient-level data from 40 138 bleeding patients. Lancet. 2018;391(10116):125-132. https://pubmed.ncbi.nlm.nih.gov/29126600/ Levy JH, Koster A, Quinones QJ, Milling TJ, Key NS. Antifibrinolytic Therapy and Perioperative Considerations. Anesthesiology. 2018;128(3):657‐ https://pubmed.ncbi.nlm.nih.gov/29200009/ Perel P, Al-Shahi S, Kawahara T, et al. CRASH-2 (Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage) intracranial bleeding study: the effect of tranexamic acid in traumatic brain injury–a nested randomised, placebo-controlled trial. Health Technol Assess. 2012;16(13):iii-xii, 1-54. https://www.ncbi.nlm.nih.gov/pubmed/22417901. Poeram, J., et al. Tranexamic acid use and postoperative outcomes in patients undergoing total hip or knee arthroplasty in the United states: Retrospective analysis of effectiveness and safety. BJM. Aug 2014;349:g4829. https://www.bmj.com/content/349/bmj.g4829 Roberts I, Coats T, Edwards P, et al. HALT-IT–tranexamic acid for the treatment of gastrointestinal bleeding: study protocol for a randomised controlled trial. Trials. 2014;15:450. https://www.ncbi.nlm.nih.gov/pubmed/25409738. Roberts I, Shakur H, Coats T, et al. The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients. Health Technol Assess. 2013;17(10):1-79. https://www.ncbi.nlm.nih.gov/pubmed/23477634. Salim Rezaie, "It’s Time for Tranexamic Acid (TXA) in Massive Hemorrhage", REBEL EM blog, November 20, 2017. Available at: https://rebelem.com/its-time-for-tranexamic-acid-txa-in-massive-hemorrhage/. Shakur H, Roberts I, Bautista R, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376(9734):23-32. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60835-5/fulltext Sprigg N, Flaherty K, Appleton J, et al. Tranexamic acid for hyperacute primary Intra-Cerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial. Lancet. 2018;391(10135):2107-2115. https://www.ncbi.nlm.nih.gov/pubmed/29778325. The CRASH-3 trial collaborators. Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial. Lancet. October 14, 2019. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32233-0/fulltext WOMAN trial collaborators. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial. 2017;389(10084):2105-2116. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30638-4/fulltext Zehtabchi S et al. Tranexamic Acid for Traumatic Brain Injury: A Systematic Review and Meta-Analysis. Am J Emerg Med 2014. PMID: 25447601. https://pubmed.ncbi.nlm.nih.gov/25447601/ Zhang, H., et al. The effect of tranexamic acid on blood loss and use of blood products in total knee arthroplasty: a meta-analysis. Knee Surg Sports Traumatol Arthrosc. 2012 Sep;20(9):1742-52. https://pubmed.ncbi.nlm.nih.gov/22065294/