Aminocaproic acid – an antifibrinolytic with great clinical potential
18.10.2016
Aminocaproic acid – an antifibrinolytic with great clinical potential
Aminocaproic acid (6-aminohexanoic acid or ε-aminocaproic acid) is one of the most well-known hemostatic agents. The mechanism of action of aminocaproic acid is associated with the inhibition of the conversion of profibrinolysin to fibrinolysin, apparently by inhibiting the activator of this process, as well as exerting a direct inhibitory effect on fibrinolysin; it inhibits the activating effect of streptokinase, urokinase, and tissue kinases on fibrinolysis, neutralizes the effects of kallikrein, trypsin, and hyaluronidase, and reduces capillary permeability.
Despite being one of the "veterans" among drugs with antifibrinolytic activity (clinical use began in 1962), and despite the emergence of new generations of effective hemostatic agents over more than 50 years, the significance of this drug remains high. Aminocaproic acid is mainly used perioperatively to reduce intraoperative blood loss and the risk of postoperative bleeding in traumatic and/or extensive surgeries in fields such as surgery, obstetrics and gynecology, orthopedics and traumatology. This, among other things, allows for avoiding blood transfusions and preventing post-transfusion complications.
Another effective antifibrinolytic agent, tranexamic acid, has failed to replace aminocaproic acid, which demonstrates at least similar clinical efficacy and a high safety profile, as shown in a study by K. Martin et al. (2011). In this study, aminocaproic acid and tranexamic acid were used perioperatively in 234 pediatric patients undergoing cardiac surgeries. Both drugs demonstrated similar efficacy and no statistically significant differences in the frequency of adverse reactions; however, in absolute terms, aminocaproic acid was more effective, including a lower frequency of repeat interventions for bleeding (8.3% in the aminocaproic acid group vs. 9.6% in the tranexamic acid group) and side effects such as seizures (0.8% vs. 3.5%).
It is also important to mention the local application of aminocaproic acid in the field of ENT diseases. The effectiveness of local hemostasis and a significantly lower rate of postoperative bleeding compared to placebo after sinus surgery was demonstrated in an experimental study by D.C. Thomas et al. (2008).
However, the greatest interest in aminocaproic acid, according to recent publications in the medical literature, has come from orthopedic surgeons performing joint reconstruction surgeries (total joint replacement) and spinal surgeries (scoliosis surgery in children and spinal reconstructive surgery in adults) (J.D. Eubanks, 2010). According to the results of numerous randomized placebo-controlled trials, perioperative use of aminocaproic acid contributed to reduced intraoperative blood loss, reduced need for blood transfusions, which ensured a favorable postoperative course and lowered the overall treatment cost.
Recently, the results of a meta-analysis on the effectiveness of antifibrinolytic agents in reducing intraoperative blood loss during spinal surgeries have also confirmed the effectiveness of aminocaproic acid, which is not inferior to tranexamic acid (G. Li et al., 2016). Perioperative use of antifibrinolytics prevented massive blood loss and significantly reduced the need for intra- and postoperative blood transfusions. It was also shown that the incidence of thromboembolic complications in the groups receiving antifibrinolytics was not statistically different from the control group.
To date, the optimal regimens for using antifibrinolytics during spinal surgeries have not been definitively established. However, considering the proven effectiveness of aminocaproic acid (according to the latest Cochrane review, the use of antifibrinolytics, including aminocaproic acid, in scoliosis surgery in children reduced intraoperative blood loss by 20% compared to placebo [E.D. McNicol et al., 2016]), the development of detailed guidelines is a matter of time. It is also necessary to determine the most effective concentrations of the drug in blood plasma and develop methods to maintain them during surgery and the postoperative period.
References:
1. Eubanks JD. Antifibrinolytics in major orthopaedic surgery. J Am Acad Orthop Surg. 2010 Mar;18(3):132-8.
2. Li G, Sun TW, Luo G, Zhang C. Efficacy of antifibrinolytic agents on surgical bleeding and transfusion requirements in spine surgery: a meta-analysis. Eur Spine J. 2016 Sep 26. [Epub ahead of print]
3. Martin K, Breuer T, Gertler R, Hapfelmeier A, Schreiber C, Lange R, Hess J, Wiesner G. Tranexamic acid versus ɛ-aminocaproic acid: efficacy and safety in paediatric cardiac surgery. Eur J Cardiothorac Surg. 2011 Jun;39(6):892-7.
4. McNicol ED, Tzortzopoulou A, Schumann R, Carr DB, Kalra A. Antifibrinolytic agents for reducing blood loss in scoliosis surgery in children. Cochrane Database Syst Rev. 2016 Sep 19;9:CD006883. [Epub ahead of print]
5. Nielsen VG, Cankovic L, Steenwyk BL.Epsilon-aminocaproic acid inhibition of fibrinolysis in vitro: should the 'therapeutic' concentration be reconsidered? Blood Coagul Fibrinolysis. 2007 Jan;18(1):35-9.
6. Thomas DC, Wormald PJ. A randomized controlled pilot study of epsilon-aminocaproic acid as a topical hemostatic agent for postoperative bleeding in the sheep model of chronic sinusitis. Am J Rhinol. 2008 Mar-Apr;22(2):188-91.
7. https://ru.wikipedia.org
Despite being one of the "veterans" among drugs with antifibrinolytic activity (clinical use began in 1962), and despite the emergence of new generations of effective hemostatic agents over more than 50 years, the significance of this drug remains high. Aminocaproic acid is mainly used perioperatively to reduce intraoperative blood loss and the risk of postoperative bleeding in traumatic and/or extensive surgeries in fields such as surgery, obstetrics and gynecology, orthopedics and traumatology. This, among other things, allows for avoiding blood transfusions and preventing post-transfusion complications.
Another effective antifibrinolytic agent, tranexamic acid, has failed to replace aminocaproic acid, which demonstrates at least similar clinical efficacy and a high safety profile, as shown in a study by K. Martin et al. (2011). In this study, aminocaproic acid and tranexamic acid were used perioperatively in 234 pediatric patients undergoing cardiac surgeries. Both drugs demonstrated similar efficacy and no statistically significant differences in the frequency of adverse reactions; however, in absolute terms, aminocaproic acid was more effective, including a lower frequency of repeat interventions for bleeding (8.3% in the aminocaproic acid group vs. 9.6% in the tranexamic acid group) and side effects such as seizures (0.8% vs. 3.5%).
It is also important to mention the local application of aminocaproic acid in the field of ENT diseases. The effectiveness of local hemostasis and a significantly lower rate of postoperative bleeding compared to placebo after sinus surgery was demonstrated in an experimental study by D.C. Thomas et al. (2008).
However, the greatest interest in aminocaproic acid, according to recent publications in the medical literature, has come from orthopedic surgeons performing joint reconstruction surgeries (total joint replacement) and spinal surgeries (scoliosis surgery in children and spinal reconstructive surgery in adults) (J.D. Eubanks, 2010). According to the results of numerous randomized placebo-controlled trials, perioperative use of aminocaproic acid contributed to reduced intraoperative blood loss, reduced need for blood transfusions, which ensured a favorable postoperative course and lowered the overall treatment cost.
Recently, the results of a meta-analysis on the effectiveness of antifibrinolytic agents in reducing intraoperative blood loss during spinal surgeries have also confirmed the effectiveness of aminocaproic acid, which is not inferior to tranexamic acid (G. Li et al., 2016). Perioperative use of antifibrinolytics prevented massive blood loss and significantly reduced the need for intra- and postoperative blood transfusions. It was also shown that the incidence of thromboembolic complications in the groups receiving antifibrinolytics was not statistically different from the control group.
To date, the optimal regimens for using antifibrinolytics during spinal surgeries have not been definitively established. However, considering the proven effectiveness of aminocaproic acid (according to the latest Cochrane review, the use of antifibrinolytics, including aminocaproic acid, in scoliosis surgery in children reduced intraoperative blood loss by 20% compared to placebo [E.D. McNicol et al., 2016]), the development of detailed guidelines is a matter of time. It is also necessary to determine the most effective concentrations of the drug in blood plasma and develop methods to maintain them during surgery and the postoperative period.
References:
1. Eubanks JD. Antifibrinolytics in major orthopaedic surgery. J Am Acad Orthop Surg. 2010 Mar;18(3):132-8.
2. Li G, Sun TW, Luo G, Zhang C. Efficacy of antifibrinolytic agents on surgical bleeding and transfusion requirements in spine surgery: a meta-analysis. Eur Spine J. 2016 Sep 26. [Epub ahead of print]
3. Martin K, Breuer T, Gertler R, Hapfelmeier A, Schreiber C, Lange R, Hess J, Wiesner G. Tranexamic acid versus ɛ-aminocaproic acid: efficacy and safety in paediatric cardiac surgery. Eur J Cardiothorac Surg. 2011 Jun;39(6):892-7.
4. McNicol ED, Tzortzopoulou A, Schumann R, Carr DB, Kalra A. Antifibrinolytic agents for reducing blood loss in scoliosis surgery in children. Cochrane Database Syst Rev. 2016 Sep 19;9:CD006883. [Epub ahead of print]
5. Nielsen VG, Cankovic L, Steenwyk BL.Epsilon-aminocaproic acid inhibition of fibrinolysis in vitro: should the 'therapeutic' concentration be reconsidered? Blood Coagul Fibrinolysis. 2007 Jan;18(1):35-9.
6. Thomas DC, Wormald PJ. A randomized controlled pilot study of epsilon-aminocaproic acid as a topical hemostatic agent for postoperative bleeding in the sheep model of chronic sinusitis. Am J Rhinol. 2008 Mar-Apr;22(2):188-91.
7. https://ru.wikipedia.org
