Art & science | coagulopathy
Tranexamic acid in patients with major injuries and blood loss Carl Livingstone reviews two trials of a blood‑clotting agent involving people who had sustained traumatic injuries with significant exsanguination Correspondence [email protected] Carl Livingstone is an emergency department staff nurse at North Bristol NHS Trust Date of submission August 28 2013 Date of acceptance September 23 2013 Peer review This article has been subject to double-blind review and has been checked using antiplagiarism software Author guidelines en.rcnpublishing.com
Abstract In the UK, care for people with major injuries has improved since the introduction of trauma networks and major trauma centres, and since ambulance services began to use specific triage tools to identify major trauma. The advent of consultant-led trauma teams in emergency departments and implementation of the relevant protocols have also raised the standard of trauma care. One such protocol governs the use of tranexamic acid (TXA), which is used to control bleeding. This drug is cheap and widely available, and can save lives if administered within three hours of injury. This article reviews two recent major studies of the effects of TXA on trauma patients Keywords Major injury, blood loss, trauma care, tranexamic acid AVAILABLE FOR more than 40 years, tranexamic acid (TXA) has been used successfully to control and reduce bleeding in patients with haemophilia, heavy menstrual bleeding, and in those undergoing elective cardiac and orthopaedic surgery (Martin et al 2008, 2011, Henry et al 2009, Kagoma et al 2009, Sander et al 2010, Boling and Moore 2012). Tranexamic acid is an antifibrinolytic that acts primarily by binding to plasminogen and interfering with its conversion to plasmin, thereby inhibiting fibrinolysis and diminishing blood loss (Ide et al 2010). It also reduces the inflammatory response that is thought to contribute to the development of multiple organ dysfunction syndrome secondary to haemorrhagic shock (Levy 2010, Cap et al 2011). The onset of fibrinolysis after traumatic injury is rapid (Kashuk et al 2010) but is detectable within 30 minutes of injury (Davenport et al 2011),
24 December 2013 | Volume 21 | Number 8
so outcomes of TXA use can depend on time of administration. Coagulopathy after major trauma is usually attributed to activation and consumption of coagulation factors, such as hypothermia and metabolic acidosis, while early coapulapathy is due to tissue hypoperfusion (Tsuei and Kearny 2004). Not all trauma patients become coagulapathic, but those who do are more likely to die (Mitra et al 2010). One of the contraindications for TXA is thromboembolic disease, which increases the risk of deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE). Use of TXA increased after publication of two major studies: the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH)-2 trial (Shakur et al 2010) and the Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTER) trial (Morrison et al 2012), both of which are reviewed below.
Review of studies Study one The CRASH-2 trial was a UK governmentfunded, multi-country randomised trial of the effects of early administration of TXA on the likelihood of death and vascular occlusive events, and the need for blood transfusion, in bleeding trauma patients. It was conducted in 274 study sites, most of which were in low- and middle-income countries, and involved 20,211 participants who had sustained traumatic injuries, some involving significant haemorrhage, within the previous eight hours. Ten thousand and sixty patients were given a loading dose of 1g intravenous TXA over ten minutes followed by an infusion of 1g over eight hours, and 10,151 patients were given
EMERGENCY NURSE Downloaded from rcnpublishing.com by ${individualUser.displayName} on Feb 12, 2015. For personal use only. No other uses without permission. Copyright © 2015 RCN Publishing Ltd. All rights reserved.
matching placebos. Of the 1,063 patients who died from haemorrhage, 489 had been given TXA and 574 had been given placebos, representing 4.9 per cent of the TXA group and 5.7 per cent of the placebo group respectively. These figures suggest that administration of TXA can reduce the risk of death from bleeding. Drugs were administered within one hour of, between one and three hours after, or more than three hours after injury. Results show that: ■■ Of 3,747 patients given TXA within one hour of injury, 198 (5.3 per cent) died. ■■ Of 3,704 patients given placebos within one hour of injury, 286 (7.7 per cent) died. ■■ Of 3,037 patients given TXA between one and three hours after injury, 147 (4.8 per cent) died. ■■ Of 2,996 patients given placebos between one and three hours after injury, 184 (6.1 per cent) died. ■■ Of 3,272 patients given TXA more than three hours after injury, 144 (4.4 per cent) died. ■■ Of 3,362 patients given placebos more than three hours after injury, 103 (3.1 per cent) died. These results indicate that the effect of TXA on death due to bleeding depends on the time from injury that it is administered. The CRASH-2 trial did not measure coagulopathy markers or record if patients received blood transfusion, fresh frozen plasma (FFP), platelets or cryoprecipitate. The study was conducted in mainly low- or middle-GDP countries, in which trauma centres may be unable to afford the use of major haemorrhage protocols. Blood transfusions, FFP, platelets and cryoprecipitate are effective when used during significant bleeding and coagulopathy but are expensive, while TXA is practical, affordable and effective when administered within three hours of injury (Mitra and Gruen 2011). The cost of TXA is £1.55 per 5ml ampoule (100mg/ml). If two ampoules are needed for the loading dose and two more for the maintenance doses, the total cost would be about £6.20, which compares with £120 for one unit of packed red blood cells (PRBCs). Study two The MATTERs study was conducted jointly between the UK Joint Medical Command Research Pillar and the US Army’s Medical Research and Materiel Command. It was a retrospective study of events between January 1 2009 and December 31 2010 at Camp Bastion, Afghanistan. The study involved 896 patients, including military personnel, Afghan police and civilians, who had combat-related injuries and had received at least one unit of PRBCs within 24 hours of
admission to the camp’s emergency department (ED) or to its theatre. A total of 321 patients had received ten or more units of PRBCs, and these were said to have had massive transfusions (MTs). The study measured the numbers of deaths within 24 hours of injury, between 24 and 48 hours after injury, and within 30 days of admission to hospital. Each patient was given three scores: an abbreviated injury score, a first coagulopathy score at admission to the ED or theatre and a second coagulopathy score on arrival at the intensive care unit (ICU) following the initial operation. Of all 896 patients involved in the study, 293 had received TXA and 603 had not. Three hundred and twenty one patients had received MT and, of these, 125 had also received TXA and 196 had not. These groups of patients were labelled TXA, no-TXA, TXAmt and no-TXAmt respectively. Results show that 145 (50 per cent) of the patients in the TXA group, 385 (64 per cent) of those in the no-TXA group, 54 (43 per cent) of those in the TXAmt group and 125 (64 per cent) in the no-TXAmt group had died within 30 days of admission to hospital. These findings suggest that TXA improves markers of coagulation and reduces the risk of death. The study also revealed an increase in DVT and PTE among all patients who had received TXA. These patients tended to have higher injury scores, however, so whether the increase in incidence of DVT and PTE is due to the potential prothrombotic mechanism of TXA or to severity of injury is unknown. Overall, the MATTERs findings suggest that TXA is more beneficial in higher severity traumatic injuries and is more effective when used with massive transfusion protocols covering, for example, blood transfusion, FFP, platelets and cryoprecipitate
Conclusion The studies discussed in this article involved patients with traumatic injuries. Participants in the CRASH-2 trial had mainly blunt trauma injuries, while those in the MATTERs trial had more penetrating injuries. Unlike the CRASH-2 trial, the MATTERs study recorded severity of injury score and area of injury, which gives a clearer picture of which patients benefit more from TXA. The studies highlight the importance of using TXA in trauma patients and show that early administration improves survival rates and outcomes. They also show that the drug should be administered to trauma patients within four hours of injury, after which it is unlikely to be effective.
EMERGENCY NURSE December 2013 | Volume 21 | Number 8 25 Downloaded from rcnpublishing.com by ${individualUser.displayName} on Feb 12, 2015. For personal use only. No other uses without permission. Copyright © 2015 RCN Publishing Ltd. All rights reserved.
Art & science | coagulopathy After the CRASH-2 trial results had been published, the World Health Organization (WHO) included TXA on its list of essential medicines and attempted to increase awareness of TXA’s potential for saving the lives of trauma patients. The CRASH-2 trial concludes that, if TXA is administered within one hour of injury, 128,000 deaths worldwide could be prevented; if it is administered within three hours of injury, 112,000 deaths worldwide could be prevented (Ker et al 2012). Since the implementation of trauma networks, the treatment of trauma patients has improved. Most haemodynaically stable trauma patients are transported by road or air to the nearest trauma centre. Haemodynaically unstable trauma patients, or patients who would have to travel for more than
30 minutes to a trauma centre, usually attend the nearest trauma unit for stabilisation before transfer to the centre. Ambulance services use trauma triage tools to assess whether patients should be assigned to the trauma category. With critical care paramedics and doctors on the front line, and the air ambulance service in operation during daylight, trauma patients should receive the best treatment possible. As trauma protocols, tools and appropriate clinical guidance are introduced, the use of TXA is increasing. Inexpensive, and easy to store on ambulances and rapid response vehicles, it is proven to reduce blood loss and death from severe haemorrhage. As long as TXA is administered by paramedics at incident sites and at the earliest opportunities, survival rates are likely to improve.
Online archive For related information, visit our online archive and search using the keywords Conflict of interest None declared
References Boling B, Moore K (2012) Tanexamic acid (TXA) use in trauma. Journal of Emergency Nursing. 38, 496-497.
in cardiac surgery. Journal of Anesthesia. 24, 1, 96-106.
Cap AP, Baer DG, Orman JA et al (2011) Tranexamic acid for trauma patients: a critical review of the literature. Journal of Trauma. 71, Supplement 1, S9-S14. doi: 10.1097/TA.0b013e31822114af
Kagoma Y, Crowther M, Douketis J et al (2009) Use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopaedic surgery: a systemic review of randomized trials. Thrombosis Research. 123, 5, 687-696. doi: 10.1016/j.thromres.2008.09.015
Davenport R, Curry N, Manson J et al (2011) Hemostatic effects of fresh frozen plasma may be maximal at red cell ratios of 1:2. Journal of Trauma. 70, 1, 90-95.
Kashuk JL, Moore EE, Sawyer M et al (2010) Primary fibrinolysis is integral in the pathogenesis of the acute coagulathy of trauma. Annals of Surgery. 252, 3, 434-44.
Henry D, Carless P, Fergusson D et al (2009) The safety of aprotinin and lysine-derived antifibrinolytic drugs in cardiac surgery: a meta-analysis. Canadian Medical Association Journal. 180, 2, 183-193.
Ker K, Kiriya J, Perel P et al (2012) Avoidable mortality from giving tranexamic acid to bleeding trauma patients: an estimation based on WHO mortality data, a systemic literature review and data from CRASH‑2 trail. BMC Emergency Medicine. 12, 3. doi:10.1186/1471-227X-12-3
Ide M, Bolliger D, Taketomi T et al (2010) Lessons from the aprotinin saga: current perspective on antifibrinolytic therapy
26 December 2013 | Volume 21 | Number 8
Levy JH (2010) Antifibrinolytic therapy: new data and new concepts. The Lancet. 376, 9734, 3-4. Martin K, Wiesner G, Breuer T et al (2008) The risks of aprotinin and tranexamic acid in cardiac surgery: a one-year follow-up of 1188 consecutive patients. Anesthesia and Analgesia. 107, 6, 1783-1790. doi: 10.1213/ane.0b013e318184bc20 Martin K, Knorr J, Breuer T et al (2011) Seizures after open heart surgery: comparison of epsilon-aminocaproic acid and tranexamic acid. Journal of Cardiothoracic and Vascular Anesthesia. 25, 1, 20-25. Mitra B, Cameron P, Mori A et al (2010) Acute coagulopathy and early deaths post major trauma. Injury. doi: 10.1016/j.injury.2010.10.015 Mitra B, Gruen R (2011) Tranexamic acid for trauma. The Lancet. doi:10.1016/S0140-6736(11)60396-6
Morrison JJ, Dubose JJ, Rasmussen TE et al (2012) Military application of tranexamic acid in trauma emergency resuscitation (MATTERs) study. Archives of Surgery. 147, 2, 113-119. doi: 10.1001/archsurg.2011.287 Sander M, Spies C, Martiny V et al (2010) Mortality associated with administration of high-dose tranexamic acid and aprotinin in primary open-heart procedures: a retrospective analysis. Critical Care. 14, 4, 148. doi: 10.1186/cc9216 Shakur H, Roberts R, Bautista R et al (2010) 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. The Lancet. 376, 23-32. Tsuei B, Kearny P (2004) Hypothermia in the trauma patient. Injury. 35, 1, 7-15.
EMERGENCY NURSE Downloaded from rcnpublishing.com by ${individualUser.displayName} on Feb 12, 2015. For personal use only. No other uses without permission. Copyright © 2015 RCN Publishing Ltd. All rights reserved.
Tranexamic acid in patients with major injuries and blood loss Carl Livingstone reviews two trials of a blood‑clotting agent involving people who had sustained traumatic injuries with significant exsanguination Correspondence [email protected] Carl Livingstone is an emergency department staff nurse at North Bristol NHS Trust Date of submission August 28 2013 Date of acceptance September 23 2013 Peer review This article has been subject to double-blind review and has been checked using antiplagiarism software Author guidelines en.rcnpublishing.com
Abstract In the UK, care for people with major injuries has improved since the introduction of trauma networks and major trauma centres, and since ambulance services began to use specific triage tools to identify major trauma. The advent of consultant-led trauma teams in emergency departments and implementation of the relevant protocols have also raised the standard of trauma care. One such protocol governs the use of tranexamic acid (TXA), which is used to control bleeding. This drug is cheap and widely available, and can save lives if administered within three hours of injury. This article reviews two recent major studies of the effects of TXA on trauma patients Keywords Major injury, blood loss, trauma care, tranexamic acid AVAILABLE FOR more than 40 years, tranexamic acid (TXA) has been used successfully to control and reduce bleeding in patients with haemophilia, heavy menstrual bleeding, and in those undergoing elective cardiac and orthopaedic surgery (Martin et al 2008, 2011, Henry et al 2009, Kagoma et al 2009, Sander et al 2010, Boling and Moore 2012). Tranexamic acid is an antifibrinolytic that acts primarily by binding to plasminogen and interfering with its conversion to plasmin, thereby inhibiting fibrinolysis and diminishing blood loss (Ide et al 2010). It also reduces the inflammatory response that is thought to contribute to the development of multiple organ dysfunction syndrome secondary to haemorrhagic shock (Levy 2010, Cap et al 2011). The onset of fibrinolysis after traumatic injury is rapid (Kashuk et al 2010) but is detectable within 30 minutes of injury (Davenport et al 2011),
24 December 2013 | Volume 21 | Number 8
so outcomes of TXA use can depend on time of administration. Coagulopathy after major trauma is usually attributed to activation and consumption of coagulation factors, such as hypothermia and metabolic acidosis, while early coapulapathy is due to tissue hypoperfusion (Tsuei and Kearny 2004). Not all trauma patients become coagulapathic, but those who do are more likely to die (Mitra et al 2010). One of the contraindications for TXA is thromboembolic disease, which increases the risk of deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE). Use of TXA increased after publication of two major studies: the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH)-2 trial (Shakur et al 2010) and the Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTER) trial (Morrison et al 2012), both of which are reviewed below.
Review of studies Study one The CRASH-2 trial was a UK governmentfunded, multi-country randomised trial of the effects of early administration of TXA on the likelihood of death and vascular occlusive events, and the need for blood transfusion, in bleeding trauma patients. It was conducted in 274 study sites, most of which were in low- and middle-income countries, and involved 20,211 participants who had sustained traumatic injuries, some involving significant haemorrhage, within the previous eight hours. Ten thousand and sixty patients were given a loading dose of 1g intravenous TXA over ten minutes followed by an infusion of 1g over eight hours, and 10,151 patients were given
EMERGENCY NURSE Downloaded from rcnpublishing.com by ${individualUser.displayName} on Feb 12, 2015. For personal use only. No other uses without permission. Copyright © 2015 RCN Publishing Ltd. All rights reserved.
matching placebos. Of the 1,063 patients who died from haemorrhage, 489 had been given TXA and 574 had been given placebos, representing 4.9 per cent of the TXA group and 5.7 per cent of the placebo group respectively. These figures suggest that administration of TXA can reduce the risk of death from bleeding. Drugs were administered within one hour of, between one and three hours after, or more than three hours after injury. Results show that: ■■ Of 3,747 patients given TXA within one hour of injury, 198 (5.3 per cent) died. ■■ Of 3,704 patients given placebos within one hour of injury, 286 (7.7 per cent) died. ■■ Of 3,037 patients given TXA between one and three hours after injury, 147 (4.8 per cent) died. ■■ Of 2,996 patients given placebos between one and three hours after injury, 184 (6.1 per cent) died. ■■ Of 3,272 patients given TXA more than three hours after injury, 144 (4.4 per cent) died. ■■ Of 3,362 patients given placebos more than three hours after injury, 103 (3.1 per cent) died. These results indicate that the effect of TXA on death due to bleeding depends on the time from injury that it is administered. The CRASH-2 trial did not measure coagulopathy markers or record if patients received blood transfusion, fresh frozen plasma (FFP), platelets or cryoprecipitate. The study was conducted in mainly low- or middle-GDP countries, in which trauma centres may be unable to afford the use of major haemorrhage protocols. Blood transfusions, FFP, platelets and cryoprecipitate are effective when used during significant bleeding and coagulopathy but are expensive, while TXA is practical, affordable and effective when administered within three hours of injury (Mitra and Gruen 2011). The cost of TXA is £1.55 per 5ml ampoule (100mg/ml). If two ampoules are needed for the loading dose and two more for the maintenance doses, the total cost would be about £6.20, which compares with £120 for one unit of packed red blood cells (PRBCs). Study two The MATTERs study was conducted jointly between the UK Joint Medical Command Research Pillar and the US Army’s Medical Research and Materiel Command. It was a retrospective study of events between January 1 2009 and December 31 2010 at Camp Bastion, Afghanistan. The study involved 896 patients, including military personnel, Afghan police and civilians, who had combat-related injuries and had received at least one unit of PRBCs within 24 hours of
admission to the camp’s emergency department (ED) or to its theatre. A total of 321 patients had received ten or more units of PRBCs, and these were said to have had massive transfusions (MTs). The study measured the numbers of deaths within 24 hours of injury, between 24 and 48 hours after injury, and within 30 days of admission to hospital. Each patient was given three scores: an abbreviated injury score, a first coagulopathy score at admission to the ED or theatre and a second coagulopathy score on arrival at the intensive care unit (ICU) following the initial operation. Of all 896 patients involved in the study, 293 had received TXA and 603 had not. Three hundred and twenty one patients had received MT and, of these, 125 had also received TXA and 196 had not. These groups of patients were labelled TXA, no-TXA, TXAmt and no-TXAmt respectively. Results show that 145 (50 per cent) of the patients in the TXA group, 385 (64 per cent) of those in the no-TXA group, 54 (43 per cent) of those in the TXAmt group and 125 (64 per cent) in the no-TXAmt group had died within 30 days of admission to hospital. These findings suggest that TXA improves markers of coagulation and reduces the risk of death. The study also revealed an increase in DVT and PTE among all patients who had received TXA. These patients tended to have higher injury scores, however, so whether the increase in incidence of DVT and PTE is due to the potential prothrombotic mechanism of TXA or to severity of injury is unknown. Overall, the MATTERs findings suggest that TXA is more beneficial in higher severity traumatic injuries and is more effective when used with massive transfusion protocols covering, for example, blood transfusion, FFP, platelets and cryoprecipitate
Conclusion The studies discussed in this article involved patients with traumatic injuries. Participants in the CRASH-2 trial had mainly blunt trauma injuries, while those in the MATTERs trial had more penetrating injuries. Unlike the CRASH-2 trial, the MATTERs study recorded severity of injury score and area of injury, which gives a clearer picture of which patients benefit more from TXA. The studies highlight the importance of using TXA in trauma patients and show that early administration improves survival rates and outcomes. They also show that the drug should be administered to trauma patients within four hours of injury, after which it is unlikely to be effective.
EMERGENCY NURSE December 2013 | Volume 21 | Number 8 25 Downloaded from rcnpublishing.com by ${individualUser.displayName} on Feb 12, 2015. For personal use only. No other uses without permission. Copyright © 2015 RCN Publishing Ltd. All rights reserved.
Art & science | coagulopathy After the CRASH-2 trial results had been published, the World Health Organization (WHO) included TXA on its list of essential medicines and attempted to increase awareness of TXA’s potential for saving the lives of trauma patients. The CRASH-2 trial concludes that, if TXA is administered within one hour of injury, 128,000 deaths worldwide could be prevented; if it is administered within three hours of injury, 112,000 deaths worldwide could be prevented (Ker et al 2012). Since the implementation of trauma networks, the treatment of trauma patients has improved. Most haemodynaically stable trauma patients are transported by road or air to the nearest trauma centre. Haemodynaically unstable trauma patients, or patients who would have to travel for more than
30 minutes to a trauma centre, usually attend the nearest trauma unit for stabilisation before transfer to the centre. Ambulance services use trauma triage tools to assess whether patients should be assigned to the trauma category. With critical care paramedics and doctors on the front line, and the air ambulance service in operation during daylight, trauma patients should receive the best treatment possible. As trauma protocols, tools and appropriate clinical guidance are introduced, the use of TXA is increasing. Inexpensive, and easy to store on ambulances and rapid response vehicles, it is proven to reduce blood loss and death from severe haemorrhage. As long as TXA is administered by paramedics at incident sites and at the earliest opportunities, survival rates are likely to improve.
Online archive For related information, visit our online archive and search using the keywords Conflict of interest None declared
References Boling B, Moore K (2012) Tanexamic acid (TXA) use in trauma. Journal of Emergency Nursing. 38, 496-497.
in cardiac surgery. Journal of Anesthesia. 24, 1, 96-106.
Cap AP, Baer DG, Orman JA et al (2011) Tranexamic acid for trauma patients: a critical review of the literature. Journal of Trauma. 71, Supplement 1, S9-S14. doi: 10.1097/TA.0b013e31822114af
Kagoma Y, Crowther M, Douketis J et al (2009) Use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopaedic surgery: a systemic review of randomized trials. Thrombosis Research. 123, 5, 687-696. doi: 10.1016/j.thromres.2008.09.015
Davenport R, Curry N, Manson J et al (2011) Hemostatic effects of fresh frozen plasma may be maximal at red cell ratios of 1:2. Journal of Trauma. 70, 1, 90-95.
Kashuk JL, Moore EE, Sawyer M et al (2010) Primary fibrinolysis is integral in the pathogenesis of the acute coagulathy of trauma. Annals of Surgery. 252, 3, 434-44.
Henry D, Carless P, Fergusson D et al (2009) The safety of aprotinin and lysine-derived antifibrinolytic drugs in cardiac surgery: a meta-analysis. Canadian Medical Association Journal. 180, 2, 183-193.
Ker K, Kiriya J, Perel P et al (2012) Avoidable mortality from giving tranexamic acid to bleeding trauma patients: an estimation based on WHO mortality data, a systemic literature review and data from CRASH‑2 trail. BMC Emergency Medicine. 12, 3. doi:10.1186/1471-227X-12-3
Ide M, Bolliger D, Taketomi T et al (2010) Lessons from the aprotinin saga: current perspective on antifibrinolytic therapy
26 December 2013 | Volume 21 | Number 8
Levy JH (2010) Antifibrinolytic therapy: new data and new concepts. The Lancet. 376, 9734, 3-4. Martin K, Wiesner G, Breuer T et al (2008) The risks of aprotinin and tranexamic acid in cardiac surgery: a one-year follow-up of 1188 consecutive patients. Anesthesia and Analgesia. 107, 6, 1783-1790. doi: 10.1213/ane.0b013e318184bc20 Martin K, Knorr J, Breuer T et al (2011) Seizures after open heart surgery: comparison of epsilon-aminocaproic acid and tranexamic acid. Journal of Cardiothoracic and Vascular Anesthesia. 25, 1, 20-25. Mitra B, Cameron P, Mori A et al (2010) Acute coagulopathy and early deaths post major trauma. Injury. doi: 10.1016/j.injury.2010.10.015 Mitra B, Gruen R (2011) Tranexamic acid for trauma. The Lancet. doi:10.1016/S0140-6736(11)60396-6
Morrison JJ, Dubose JJ, Rasmussen TE et al (2012) Military application of tranexamic acid in trauma emergency resuscitation (MATTERs) study. Archives of Surgery. 147, 2, 113-119. doi: 10.1001/archsurg.2011.287 Sander M, Spies C, Martiny V et al (2010) Mortality associated with administration of high-dose tranexamic acid and aprotinin in primary open-heart procedures: a retrospective analysis. Critical Care. 14, 4, 148. doi: 10.1186/cc9216 Shakur H, Roberts R, Bautista R et al (2010) 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. The Lancet. 376, 23-32. Tsuei B, Kearny P (2004) Hypothermia in the trauma patient. Injury. 35, 1, 7-15.
EMERGENCY NURSE Downloaded from rcnpublishing.com by ${individualUser.displayName} on Feb 12, 2015. For personal use only. No other uses without permission. Copyright © 2015 RCN Publishing Ltd. All rights reserved.
