JBUR-4356; No. of Pages 2 burns xxx (2014) xxx–xxx
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/burns
Letter to the Editor
What is the evidence for tranexamic acid in Burns? Dear Sir, Tangential excision of large burns can lead to major blood loss and coagulopathy [1,2]. Within the literature the methods used to control blood loss in theatre are widely discussed. Such methods include early excision, the use of subcutaneous injection of adrenaline solution (to the site of excision and donor sites for skin harvest), adrenaline soaked gauzes, tourniquets and sustaining core temperature greater than 378 [1,2]. Review articles demonstrate that haemoglobin thresholds for transfusion are variable but the use of blood products has increased in recent years [1,3]. Despite this there is a lack of evidence or research studies looking at the use of tranexamic acid (TXA) in burns despite its common use in trauma. In our trust TXA has been used in an ad hoc manner during plastic surgery cases where there is a risk of blood loss. On occasion it has been used in large burns to limit blood loss from the excision of a burn and the skin graft harvest. We were surprised to find that only 1 prospective study and 1 case report could be found in the literature that has reported the use of TXA in burns [4,5]. This case report only described the use of topical TXA rather than the intravenous route most often used [5]. The prospective study of TXA had only 27 patients in the study and did not provide details of the total burn size. Although there was reduced post-operative bleeding with TXA and no evidence of venous thrombo-embolism (VTE), the study suggested further research [4]. Since the study in 2003, no other study has taken place. It is clearly evident that research is required regarding the use of TXA in burns. TXA is an anti-fibrinolytic agent. It binds to plasminogen inhibiting break down of the fibrin clot [6]. Hyperfibinolysis occurs in 2–34% of trauma [6]. However no case reports have shown this incidence in burns or the ‘second hit trauma’ following burn excision. Fibrinolysis occurs in trauma or in episodes of large volume blood loss. Severe fibrinolysis can lead to acute coagulopathy of trauma (ACOT) increasing the risk of mortality in trauma patients [6]. Post injury fibrinolysis causes protein C activation resulting in protein Va and protein VIIIa deactivation mediated by a reduction plasminogen activator 1 PA inhibitor (PAI-1). PAI-1 normally inhibits tissue §
plasminogen activator 1 (t-Pa 1) and inhibits fibrinolysis. A reduction in PAI-1 results in less clot formation, thrombin is bound and a clot more amendable to fibrinolysis [6–8]. The CRASH-2 trial has shown that TXA reduced mortality in trauma patients and its use is estimated to save up 70–100,000 lives per annum worldwide [6,9]. A Cochrane review demonstrated that TXA reduced the probability of the requirement of a blood transfusion in surgery by one third [10]. A limitation of TXA is that it has been associated with increased venous thromboembolic events (VTE) [6]. Deep Vein thrombosis (DVT) and Pulmonary Embolisms (PE) occur in 1–23% of burns patients in the literature reviewed [11]. Due to the predisposition of VTE in burns we may ask if it safe to prescribe TXA in burns. Studies of TXA in trauma have not demonstrated if there was a reduction in post-operative bleeding. Due to its antifibrinolytic qualities it would be of interest to see if there was a reduction in post surgical ooze or haematoma. Clearly this may have a significant effect on graft take. TXA was shown to reduce mortality by 32% if administered within the first 1 h of bleeding. Conversely, TXA increased the risk of mortality after 3 h [9]. Research should elicit when TXA is safe to prescribe in burns and if it is suitable for use in burns. This is of great importance as burns patients require extensive excisions which may take several hours to complete or until the patient shows signs of haemodynamic instability. We are aware of increasing use of TXA in elective surgery despite the lack of evidence of clear benefit in many such situations. Although there are clear benefits in certain trauma situations the area of burns remains uninvestigated. We would encourage our colleagues to be cautious in using TXA until there is clear evidence of benefit. The complexities of performing such research are significant and would require a large number of participants. We feel it is essential to determine if TXA (i) reduces mortality, (ii) reduces the requirement for blood transfusion, (iii) determine if TXA potentiates VTE in burns, (iv) has an effect on graft take, (v) determine when TXA should be administered and the most optimum route of administration. This will require multi centre participation and we are hoping to establish an appropriate protocol with the help of our colleagues.
Worked attributed to Plastic Surgery Department, Queen Victoria Hospital, East Grinstead, UK.
Please cite this article in press as: Walsh K. What is the evidence for tranexamic acid in Burns? Burns (2014), http://dx.doi.org/10.1016/ j.burns.2014.04.015
JBUR-4356; No. of Pages 2
2
burns xxx (2014) xxx–xxx
references
[1] Curinga G, Jain A, Feldman M, Prosciak M, Phillips B, Milner S. Red blood cell transfusion following burn. Burns 2011;37:742–52. [2] Woodson LC, Sherwood ER, Aarsland A, Talon M, Kinsky MP, Morvant EM. Anesthesia for burned patients. In: Herndon DN, editor. Total burn care. London: Saunders Co.; 2007. p. 221. [3] H e´bert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care, Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med 1999;340:409–17 [Erratum in: N Engl J Med 1999;340:1056]. [4] Jennes SMD, Degrave EMD, Despiegeleer X, Grenez O. Effect of tranexamic acid on blood loss in burn surgery: a preliminary study: 33. J Burn Care Rehabil 2003; 24:S59. [5] Tang YMJ, Chapman TWL, Brooks P. Use of tranexamic acid to reduce bleeding in burn surgery. J Plast Reconstr Surg 2011;65:684–6. [6] Napolitano LM, Cohen MJ, Cotton BA, Schreiber MA, Moore EE. Tranexamic acid in trauma: how should we use it? J Acute Care Surg 2013;74:1575–86. [7] Cohen MJ, Brohi K, Ganter MT, Manley GT, Mackersie RC, Pittet JF. Early coagulopathy after traumatic brain injury: the role of hypoperfusion and the protein C pathway. J Trauma 2007;63:1254–61.
[8] Esmon CT. The protein C pathway. Chest 2003;124(3 Suppl): 26S–32S. [9] CRASH-2 Trial Collaborators, 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;376:23. [10] 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. [11] Faucher LD, Conlon KM. Practice guidelines for deep venous thrombosis prophylaxis in burns. J Burn Care Rehabil 2007;28:661–3.
Karl Walsh* The Royal Albert and Edward Infirmary, Wigan Lane, Wigan, Lancashire WN1 2NN, UK Dariush Nikkhah Baljit Dheansa Department of Plastic Surgery, Queen Victoria Hospital, East Grinstead RH19 3DZ, UK *Corresponding author E-mail addresses: [email protected] (K. Walsh) [email protected] (D. Nikkhah) [email protected] (B. Dheansa) http://dx.doi.org/10.1016/j.burns.2014.04.015 0305-4179/# 2014 Published by Elsevier Ltd and ISBI.
Please cite this article in press as: Walsh K. What is the evidence for tranexamic acid in Burns? Burns (2014), http://dx.doi.org/10.1016/ j.burns.2014.04.015
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/burns
Letter to the Editor
What is the evidence for tranexamic acid in Burns? Dear Sir, Tangential excision of large burns can lead to major blood loss and coagulopathy [1,2]. Within the literature the methods used to control blood loss in theatre are widely discussed. Such methods include early excision, the use of subcutaneous injection of adrenaline solution (to the site of excision and donor sites for skin harvest), adrenaline soaked gauzes, tourniquets and sustaining core temperature greater than 378 [1,2]. Review articles demonstrate that haemoglobin thresholds for transfusion are variable but the use of blood products has increased in recent years [1,3]. Despite this there is a lack of evidence or research studies looking at the use of tranexamic acid (TXA) in burns despite its common use in trauma. In our trust TXA has been used in an ad hoc manner during plastic surgery cases where there is a risk of blood loss. On occasion it has been used in large burns to limit blood loss from the excision of a burn and the skin graft harvest. We were surprised to find that only 1 prospective study and 1 case report could be found in the literature that has reported the use of TXA in burns [4,5]. This case report only described the use of topical TXA rather than the intravenous route most often used [5]. The prospective study of TXA had only 27 patients in the study and did not provide details of the total burn size. Although there was reduced post-operative bleeding with TXA and no evidence of venous thrombo-embolism (VTE), the study suggested further research [4]. Since the study in 2003, no other study has taken place. It is clearly evident that research is required regarding the use of TXA in burns. TXA is an anti-fibrinolytic agent. It binds to plasminogen inhibiting break down of the fibrin clot [6]. Hyperfibinolysis occurs in 2–34% of trauma [6]. However no case reports have shown this incidence in burns or the ‘second hit trauma’ following burn excision. Fibrinolysis occurs in trauma or in episodes of large volume blood loss. Severe fibrinolysis can lead to acute coagulopathy of trauma (ACOT) increasing the risk of mortality in trauma patients [6]. Post injury fibrinolysis causes protein C activation resulting in protein Va and protein VIIIa deactivation mediated by a reduction plasminogen activator 1 PA inhibitor (PAI-1). PAI-1 normally inhibits tissue §
plasminogen activator 1 (t-Pa 1) and inhibits fibrinolysis. A reduction in PAI-1 results in less clot formation, thrombin is bound and a clot more amendable to fibrinolysis [6–8]. The CRASH-2 trial has shown that TXA reduced mortality in trauma patients and its use is estimated to save up 70–100,000 lives per annum worldwide [6,9]. A Cochrane review demonstrated that TXA reduced the probability of the requirement of a blood transfusion in surgery by one third [10]. A limitation of TXA is that it has been associated with increased venous thromboembolic events (VTE) [6]. Deep Vein thrombosis (DVT) and Pulmonary Embolisms (PE) occur in 1–23% of burns patients in the literature reviewed [11]. Due to the predisposition of VTE in burns we may ask if it safe to prescribe TXA in burns. Studies of TXA in trauma have not demonstrated if there was a reduction in post-operative bleeding. Due to its antifibrinolytic qualities it would be of interest to see if there was a reduction in post surgical ooze or haematoma. Clearly this may have a significant effect on graft take. TXA was shown to reduce mortality by 32% if administered within the first 1 h of bleeding. Conversely, TXA increased the risk of mortality after 3 h [9]. Research should elicit when TXA is safe to prescribe in burns and if it is suitable for use in burns. This is of great importance as burns patients require extensive excisions which may take several hours to complete or until the patient shows signs of haemodynamic instability. We are aware of increasing use of TXA in elective surgery despite the lack of evidence of clear benefit in many such situations. Although there are clear benefits in certain trauma situations the area of burns remains uninvestigated. We would encourage our colleagues to be cautious in using TXA until there is clear evidence of benefit. The complexities of performing such research are significant and would require a large number of participants. We feel it is essential to determine if TXA (i) reduces mortality, (ii) reduces the requirement for blood transfusion, (iii) determine if TXA potentiates VTE in burns, (iv) has an effect on graft take, (v) determine when TXA should be administered and the most optimum route of administration. This will require multi centre participation and we are hoping to establish an appropriate protocol with the help of our colleagues.
Worked attributed to Plastic Surgery Department, Queen Victoria Hospital, East Grinstead, UK.
Please cite this article in press as: Walsh K. What is the evidence for tranexamic acid in Burns? Burns (2014), http://dx.doi.org/10.1016/ j.burns.2014.04.015
JBUR-4356; No. of Pages 2
2
burns xxx (2014) xxx–xxx
references
[1] Curinga G, Jain A, Feldman M, Prosciak M, Phillips B, Milner S. Red blood cell transfusion following burn. Burns 2011;37:742–52. [2] Woodson LC, Sherwood ER, Aarsland A, Talon M, Kinsky MP, Morvant EM. Anesthesia for burned patients. In: Herndon DN, editor. Total burn care. London: Saunders Co.; 2007. p. 221. [3] H e´bert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care, Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med 1999;340:409–17 [Erratum in: N Engl J Med 1999;340:1056]. [4] Jennes SMD, Degrave EMD, Despiegeleer X, Grenez O. Effect of tranexamic acid on blood loss in burn surgery: a preliminary study: 33. J Burn Care Rehabil 2003; 24:S59. [5] Tang YMJ, Chapman TWL, Brooks P. Use of tranexamic acid to reduce bleeding in burn surgery. J Plast Reconstr Surg 2011;65:684–6. [6] Napolitano LM, Cohen MJ, Cotton BA, Schreiber MA, Moore EE. Tranexamic acid in trauma: how should we use it? J Acute Care Surg 2013;74:1575–86. [7] Cohen MJ, Brohi K, Ganter MT, Manley GT, Mackersie RC, Pittet JF. Early coagulopathy after traumatic brain injury: the role of hypoperfusion and the protein C pathway. J Trauma 2007;63:1254–61.
[8] Esmon CT. The protein C pathway. Chest 2003;124(3 Suppl): 26S–32S. [9] CRASH-2 Trial Collaborators, 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;376:23. [10] 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. [11] Faucher LD, Conlon KM. Practice guidelines for deep venous thrombosis prophylaxis in burns. J Burn Care Rehabil 2007;28:661–3.
Karl Walsh* The Royal Albert and Edward Infirmary, Wigan Lane, Wigan, Lancashire WN1 2NN, UK Dariush Nikkhah Baljit Dheansa Department of Plastic Surgery, Queen Victoria Hospital, East Grinstead RH19 3DZ, UK *Corresponding author E-mail addresses: [email protected] (K. Walsh) [email protected] (D. Nikkhah) [email protected] (B. Dheansa) http://dx.doi.org/10.1016/j.burns.2014.04.015 0305-4179/# 2014 Published by Elsevier Ltd and ISBI.
Please cite this article in press as: Walsh K. What is the evidence for tranexamic acid in Burns? Burns (2014), http://dx.doi.org/10.1016/ j.burns.2014.04.015
