Pharmacological adjuncts to stop bleeding: options and effectiveness

European Journal of Trauma and Emergency Surgery

Volumn 42, Issue 3, 2016, Pages 303-310

  Panteli, M ^a   Pountos, I ^a   Giannoudis, P V ^a,b  

^a UNIVERSITY OF LEEDS   (United Kingdom)

^b CHAPEL ALLERTON HOSPITAL   (United Kingdom)

Author keywords

Antifibrinolytics; Bleeding; Coagulopathy; Haemostasis; Tranexamic acid; Trauma

Indexed keywords

ANTIFIBRINOLYTIC AGENT; TRANEXAMIC ACID;

ACIDOSIS; BLOOD CLOTTING TEST; BLOOD COAGULATION DISORDERS; BLOOD TRANSFUSION; CLINICAL PROTOCOL; COMPLICATION; FIBRINOLYSIS; HEMORRHAGE; HUMAN; HYPOTHERMIA; MULTIPLE TRAUMA; PATHOPHYSIOLOGY; PROCEDURES;

ACIDOSIS; ANTIFIBRINOLYTIC AGENTS; BLOOD COAGULATION DISORDERS; BLOOD COAGULATION TESTS; BLOOD TRANSFUSION; CLINICAL PROTOCOLS; FIBRINOLYSIS; HEMORRHAGE; HUMANS; HYPOTHERMIA; MULTIPLE TRAUMA; TRANEXAMIC ACID;

EID: 84949633757     PISSN: 18639933     EISSN: 16153146     Source Type: Journal    
DOI: 10.1007/s00068-015-0613-x     Document Type: Review

References (61)

1. Probst C, Pape HC, Hildebrand F, Regel G, Mahlke L, Giannoudis P, et al. 30 years of polytrauma care: an analysis of the change in strategies and results of 4849 cases treated at a single institution. Injury. 2009;40(1):77–83. doi:10.1016/j.injury.2008.10.004.
2. West SD, Goldberg D, Ziegler A, Krencicki M, Du Clos TW, Mold C. Transforming growth factor-beta, macrophage colony-stimulating factor and C-reactive protein levels correlate with CD14(high)CD16+ monocyte induction and activation in trauma patients. PLoS One. 2012;7(12):e52406. doi:10.1371/journal.pone.0052406.
3. Giannoudis PV, Kanakaris NK. The unresolved issue of health economics and polytrauma: the UK perspective. Injury. 2008;39(7):705–9. doi:10.1016/j.injury.2008.02.016.
4. Vu EN, Schlamp RS, Wand RT, Kleine-Deters GA, Vu MP, Tallon JM. Prehospital use of tranexamic acid for hemorrhagic shock in primary and secondary air medical evacuation. Air Med J. 2013;32(5):289–92. doi:10.1016/j.amj.2013.05.001.
5. Geeraedts LM Jr, Kaasjager HA, van Vugt AB, Frolke JP. Exsanguination in trauma: a review of diagnostics and treatment options. Injury. 2009;40(1):11–20. doi:10.1016/j.injury.2008.10.007.
6. Smith AH, Laird C, Porter K, Bloch M. Haemostatic dressings in prehospital care. Emerg Med J. 2013;30(10):784–9. doi:10.1136/emermed-2012-201581.
7. Kauvar DS, Lefering R, Wade CE. Impact of hemorrhage on trauma outcome: an overview of epidemiology, clinical presentations, and therapeutic considerations. J Trauma. 2006;60(6 Suppl):S3–11. doi:10.1097/01.ta.0000199961.02677.19.
8. Perel P, Prieto-Merino D, Shakur H, Clayton T, Lecky F, Bouamra O, et al. Predicting early death in patients with traumatic bleeding: development and validation of prognostic model. BMJ. 2012;345:e5166. doi:10.1136/bmj.e5166.
9. Findlay G, Smith N, Martin IC, Weyman D, Carter S, Mason M. Trauma: who cares? A report of the National Confidential Enquiry into Patient Outcome and Death. 2007.
10. Curry N, Hopewell S, Doree C, Hyde C, Brohi K, Stanworth S. The acute management of trauma hemorrhage: a systematic review of randomized controlled trials. Crit Care. 2011;15(2):R92. doi:10.1186/cc10096.
11. Faraoni D, Van Der Linden P. A systematic review of antifibrinolytics and massive injury. Minerva Anestesiol. 2014;80(10):1115–22 (Epub ahead of print).
12. Kirkman E, Watts S. Haemodynamic changes in trauma. Br J Anaesth. 2014;113(2):266–75. doi:10.1093/bja/aeu232.
13. Littlejohn L, Bennett BL, Drew B. Application of current hemorrhage control techniques for backcountry care: part two, hemostatic dressings and other adjuncts. Wilderness Environ Med. 2015;. doi:10.1016/j.wem.2014.08.018.
14. Spahn DR, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernandez-Mondejar E, et al. Management of bleeding and coagulopathy following major trauma: an updated European guideline. Crit Care. 2013;17(2):R76. doi:10.1186/cc12685.
15. Tien HC, Spencer F, Tremblay LN, Rizoli SB, Brenneman FD. Preventable deaths from hemorrhage at a level I Canadian trauma center. J Trauma. 2007;62(1):142–6. doi:10.1097/01.ta.0000251558.38388.47.
16. Chesters A, Roberts I, Harris T. Minimising blood loss in early trauma resuscitation. Trauma. 2014;16(1):27–36. doi:10.1177/1460408613504066.
17. Patel SV, Kidane B, Klingel M, Parry N. Risks associated with red blood cell transfusion in the trauma population, a meta-analysis. Injury. 2014;45(10):1522–33. doi:10.1016/j.injury.2014.05.015.
18. Gruen RL, Reade MC. Administer tranexamic acid early to injured patients at risk of substantial bleeding. BMJ. 2012;345:e7133. doi:10.1136/bmj.e7133.
19. Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. Military application of tranexamic acid in trauma emergency resuscitation (MATTERs) study. Arch Surg. 2012;147(2):113–9. doi:10.1001/archsurg.2011.287.
20. Nuttall GA, Bros BC, T. CR, Gessner JS, Harrison CR, Miller RD et al. Practice guidelines for perioperative blood transfusion and adjuvant therapies: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Anesthesiology. 2006;105(1):198–208.
21. Ferraris VA, Brown JR, Despotis GJ, Hammon JW, Reece TB, Saha SP, et al. 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg. 2011;91(3):944–82. doi:10.1016/j.athoracsur.2010.11.078.
22. Klenerman L, Chakrabarti R, Mackie I, Brozovic M, Stirling Y. Changes in haemostatic system after application of a tourniquet. Lancet. 1977;309(8019):970–2.
23. Ker K, Edwards P, Perel P, Shakur H, Roberts I. Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis. BMJ. 2012;344:e3054. doi:10.1136/bmj.e3054.
24. Tenholder M, Cushner FD. Intraoperative blood management in joint replacement surgery. Orthopedics. 2004;27(6 Suppl):s663–8.
25. Carson JL, Carless PA, Hebert PC. Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion. Cochrane Database Syst Rev. 2012;4:CD002042. doi:10.1002/14651858.CD002042.pub3.
26. Lemaire R. Strategies for blood management in orthopaedic and trauma surgery. J Bone Joint Surg Br. 2008;90(9):1128–36. doi:10.1302/0301-620X.90B9.21115.
27. Madjdpour C, Spahn DR. Allogeneic red blood cell transfusions: efficacy, risks, alternatives and indications. Br J Anaesth. 2005;95(1):33–42. doi:10.1093/bja/aeh290.
28. Panteli M, Papakostidis C, Dahabreh Z, Giannoudis PV. Topical tranexamic acid in total knee replacement: a systematic review and meta-analysis. Knee. 2013;20(5):300–9. doi:10.1016/j.knee.2013.05.014.
29. Spahn DR, Goodnough LT. Alternatives to blood transfusion. Lancet. 2013;381(9880):1855–65. doi:10.1016/S0140-6736(13)60808-9.
30. Pusateri AE, Holcomb JB, Kheirabadi BS, Alam HB, Wade CE, Ryan KL. Making sense of the preclinical literature on advanced hemostatic products. J Trauma. 2006;60(3):674–82. doi:10.1097/01.ta.0000196672.47783.fd.
31. Collaborators C-T, Shakur H, Roberts I, Bautista R, Caballero J, Coats T, 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. doi:10.1016/S0140-6736(10)60835-5.
32. Levy JH. Antifibrinolytic therapy: new data and new concepts. Lancet. 2010;376(9734):3–4. doi:10.1016/S0140-6736(10)60939-7.
33. Pfizer. Product information. cyklokapron (tranexamic acid). 2014. http://www.pfizer.com/system/files/products/material_safety_data/Tranexamic_Soln_Injection_16-JUL_2014.pdf. (cyklokapron). Access date 07 Dec 2015.
34. Collaborators C-T, Roberts I, Shakur H, Afolabi A, Brohi K, Coats T, et al. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet. 2011;377(9771):1096–101, 101 e1–2. doi:10.1016/S0140-6736(11)60278-X.
35. Roberts I, Perel P, Prieto-Merino D, Shakur H, Coats T, Hunt BJ, et al. Effect of tranexamic acid on mortality in patients with traumatic bleeding: prespecified analysis of data from randomised controlled trial. BMJ. 2012;345:e5839. doi:10.1136/bmj.e5839.
36. Levi M. Should antifibrinolytics be given in all patients with trauma? Curr Opin Anaesthesiol. 2012;25(3):385–8. doi:10.1097/ACO.0b013e3283532b29.
37. Dewan Y, Komolafe EO, Mejia-Mantilla JH, Perel P, Roberts I, Shakur H, et al. CRASH-3—tranexamic acid for the treatment of significant traumatic brain injury: study protocol for an international randomized, double-blind, placebo-controlled trial. Trials. 2012;13:87. doi:10.1186/1745-6215-13-87.
38. Crash-2 Collaborators IBS. Effect of tranexamic acid in traumatic brain injury: a nested randomised, placebo controlled trial (CRASH-2 Intracranial Bleeding Study). BMJ. 2011;343:d3795. doi:10.1136/bmj.d3795.
39. Yutthakasemsunt S, Kittiwatanagul W, Piyavechvirat P, Thinkamrop B, Phuenpathom N, Lumbiganon P. Tranexamic acid for patients with traumatic brain injury: a randomized, double-blinded, placebo-controlled trial. BMC Emerg Med. 2013;13:20. doi:10.1186/1471-227X-13-20.
40. Koster A, Borgermann J, Zittermann A, Lueth JU, Gillis-Januszewski T, Schirmer U. Moderate dosage of tranexamic acid during cardiac surgery with cardiopulmonary bypass and convulsive seizures: incidence and clinical outcome. Br J Anaesth. 2013;110(1):34–40. doi:10.1093/bja/aes310.
41. Gruen RL, Mitra B. Tranexamic acid for trauma. Lancet. 2011;377(9771):1052–4. doi:10.1016/S0140-6736(11)60396-6.
42. Wells JC, Stevermer JJ. PURLs: trauma care–don’t delay with TXA. J Fam Pract. 2013;62(5):E4–6.
43. Royston D. The current place of aprotinin in the management of bleeding. Anaesthesia. 2015;70 Suppl 1:46–9, e17. doi:10.1111/anae.12907.
44. Mannucci PM, Levi M. Prevention and treatment of major blood loss. N Engl J Med. 2007;356(22):2301–11. doi:10.1056/NEJMra067742.
45. Roberts I, Shakur H, Ker K, Coats T, Collaborators C-T. Antifibrinolytic drugs for acute traumatic injury. Cochrane Database Syst Rev. 2012;12:CD004896.
46. McMichan JC, Rosengarten DS, Philipp E. Prophylaxis of post-traumatic pulmonary insufficiency by protease-inhibitor therapy with aprotinin: a clinical study. Circ Shock. 1982;9(2):107–16.
47. Auer LM, Marth E, Heppner F, Holasek A. Proteolytic enzyme activity in patients with severe head injury and the effect of a proteinase inhibitor. Acta Neurochir (Wien). 1979;49(3–4):207–17.
48. Aysola AE, Wahi MM, McKelvey RP, Gerdik CR. Research on patient safety for off-label use of recombinant factor VIIa. Am J Health Syst Pharm. 2015;72(8):600–2. doi:10.2146/ajhp140493.
49. Simpson E, Lin Y, Stanworth S, Birchall J, Doree C, Hyde C. Recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia. Cochrane Database Syst Rev. 2012;3:CD005011. doi:10.1002/14651858.CD005011.pub4.
50. Levi M, Levy JH, Andersen HF, Truloff D. Safety of recombinant activated factor VII in randomized clinical trials. N Engl J Med. 2010;363(19):1791–800. doi:10.1056/NEJMoa1006221.
51. Bonville DJ, Ata A, Jahraus CB, Arnold-Lloyd T, Salem L, Rosati C, et al. Impact of preinjury warfarin and antiplatelet agents on outcomes of trauma patients. Surgery. 2011;150(4):861–8. doi:10.1016/j.surg.2011.07.070.
52. Chapman SA, Irwin ED, Beal AL, Kulinski NM, Hutson KE, Thorson MA. Prothrombin complex concentrate versus standard therapies for INR reversal in trauma patients receiving warfarin. Ann Pharmacother. 2011;45(7–8):869–75. doi:10.1345/aph.1P605.
53. Lecky FE, Omar M, Bouamra O, Jenks T, Edwards A, Battle CE, et al. The effect of preinjury warfarin use on mortality rates in trauma patients: a European multicentre study. Emerg Med J. 2015;. doi:10.1136/emermed-2014-203959.
54. Dossett LA, Riesel JN, Griffin MR, Cotton BA. Prevalence and implications of preinjury warfarin use: an analysis of the National Trauma Databank. Arch Surg. 2011;146(5):565–70. doi:10.1001/archsurg.2010.313.
55. Ivascu FA, Howells GA, Junn FS, Bair HA, Bendick PJ, Janczyk RJ. Rapid warfarin reversal in anticoagulated patients with traumatic intracranial hemorrhage reduces hemorrhage progression and mortality. J Trauma. 2005;59(5):1131–7 (discussion 7–9).
56. Rolfe S, Papadopoulos S, Cabral KP. Controversies of anticoagulation reversal in life-threatening bleeds. J Pharm Pract. 2010;23(3):217–25. doi:10.1177/0897190010362168.
57. McMillian WD, Rogers FB. Management of prehospital antiplatelet and anticoagulant therapy in traumatic head injury: a review. J Trauma. 2009;66(3):942–50. doi:10.1097/TA.0b013e3181978e7b.
58. Alvarado JC, Dewan Y, Elsayed HF, Gogichaishvili T, Gupta S, Hunt BJ, et al. Tranexamic acid in trauma: we need stronger global health policy. BMJ. 2013;347:f4593. doi:10.1136/bmj.f4593.
59. NICE Guidance. ESUOM1: Significant haemorrhage following trauma: tranexamic acid. 2012.
60. Ker K, Kiriya J, Perel P, Edwards P, Shakur H, Roberts I. Avoidable mortality from giving tranexamic acid to bleeding trauma patients: an estimation based on WHO mortality data, a systematic literature review and data from the CRASH-2 trial. BMC Emerg Med. 2012;12:3. doi:10.1186/1471-227X-12-3.
61. Guerriero C, Cairns J, Perel P, Shakur H, Roberts I, Collaborators CT. Cost-effectiveness analysis of administering tranexamic acid to bleeding trauma patients using evidence from the CRASH-2 trial. PLoS One. 2011;6(5):e18987. doi:10.1371/journal.pone.0018987.