|Year : 2015 | Volume
| Issue : 1 | Page : 21-25
Role of tranexamic acid in reducing blood loss during and after caesarean section
Simran Kaur Bhatia, Hemant Deshpande
Department of Obstetrics and Gynaecology, Padmashree Dr. D. Y. Patil Medical College Hospital and Research Centre, Pune, Maharashtra, India
|Date of Web Publication||8-Jan-2015|
Simran Kaur Bhatia
Padmashree Dr. DY Patil Medical College Hospital and Research Centre, Sant Tukaram Nagar, Pimpri, Pune - 411 018, Maharashtra
Source of Support: None, Conflict of Interest: None
Introduction: Association between caesarean section and intra operative and post operative bleeding is known. Post-partum hemorrhage is still a leading cause for maternal morbidity and mortality. This study will evaluate the efficacy and safety of tranexamic acid in reducing the blood loss after placental delivery following lower segment caesarean section (LSCS) and note any adverse effects. Materials and Methods: A total of 100 women, who underwent elective or emergency primary caesarean section at term between 37 and 41 weeks have been studied prospectively. They were divided into two groups. In the study group of 50, tranexamic acid 1 gm IV was given 20 minutes before making incision for caesarean section and the control group of 50 did not receive tranexamic acid. Statistical Analysis: For quantitative outcomes, the t-test was used to test for difference in the two groups. For categorical outcomes, chi square and odds ratio with 95% confidence interval were used as applicable. Results: The patient characteristics, namely age, height, weight, gestational age and gravidity in two groups were similar which was statistically insignificant. Hemoglobin decreased slightly after birth in both groups but no statistical difference between two groups was noticed. There was no episode of thrombosis in the study. Tranexamic acid significantly reduced the quantity of the blood loss from time of placental delivery to 2 hours postpartum (P < 0.001) and from end of LSCS to 2 hours postpartum (P < 0.001). However, there was no statistical difference in quantity of blood loss from time of placental delivery to end of LSCS in both groups (P < 0.001). Conclusion: A safe dose of tranexamic acid has an effective role in reducing blood loss during LSCS without causing adverse reaction. Thus, drug can be used effectively in reducing maternal morbidity and mortality during LSCS.
Keywords: Blood loss, delivery, labor, postpartum, tranexamic acid
|How to cite this article:|
Bhatia SK, Deshpande H. Role of tranexamic acid in reducing blood loss during and after caesarean section. Med J DY Patil Univ 2015;8:21-5
|How to cite this URL:|
Bhatia SK, Deshpande H. Role of tranexamic acid in reducing blood loss during and after caesarean section. Med J DY Patil Univ [serial online] 2015 [cited 2018 Aug 14];8:21-5. Available from: http://www.mjdrdypu.org/text.asp?2015/8/1/21/148830
| Introduction|| |
Bleeding during vaginal or operative delivery is always of prime concern. Despite significant progress in obstetric care 125,000 women die from obstetric hemorrhage annually in the world. 
The lower segment caesarean section (LSCS) is an established procedure. It involves a transverse incision on the lower uterine segment which is easier to repair and heal well. It is important to take proper steps to reduce the amount of bleeding during and after LSCS. 
Caesarean section rates have increased to as high as 25% to 30% in many areas of the world. 
In spite of the various measures to prevent blood loss during and after caesarean section, post-partum hemorrhage (PPH) continues to be the most common complication seen in almost 20% of the cases, leading to increased maternal morbidity and mortality. 
Intravenous administration of tranexamic acid (TXA) has been routinely used for many years to reduce hemorrhage during and after surgical procedures  like coronary artery bypass, scoliosis surgery, oral surgery, orthotopic liver transplantation, total hip or knee arthroplasty and urinary tract surgery. It has been shown to be very useful in reducing blood loss and incidence of blood transfusion in these surgeries.
Use of TXA has been a subject of intense debate in combat situations. Findings from MATTERs study reveal that the use of TXA in conjunction with a blood component-based resuscitation following combat injury results in improved measures of coagulopathy and survival.  This benefit was present in all who receive blood transfusions in this setting but was most prominent in those requiring massive transfusion.
This study was done to evaluate the efficacy and safety of TXA in reducing the blood loss after placental delivery following LSCS and record any adverse effects following its administration.
| Materials and Methods|| |
A prospective study of the efficacy of TXA in decreasing blood loss during and after caesarean section was carried out in department of Obstetrics and Gynecology in our hospital from 2011 to 2012. It included a total of 100 women who underwent primary caesarean section at term between 37 and 41 weeks of elective or emergency indication, between an age group of 23 and 28 years with an average height of 145-162 cm and an average body weight of 50-60 kg. They were divided into the study group which received TXA and the control group which did not receive TXA, each group consisting of 50 patients.
Patients with severe medical and surgical complications involving heart, liver or kidney, brain diseases and blood disorders, abruptio placenta, placenta previa, multiple gestation, polyhydramnios, macrosomia, obstructed and prolonged labor, previous caesarean section, allergy to TXA, history of thromboembolic disorders, severe anemia were excluded from both the groups.
Ethical approval was obtained from Institutional Ethical Committee before the commencement of the study. Patients consent was also obtained. TXA 1 gram, diluted in 10 ml distilled water was given slowly intravenously over 10 minutes in study group 20 minutes before making skin incision.
Oxytocin 10 units in 1 pint ringer lactate and 0.2 mg of methylergometrine intramuscularly were given after delivery of neonates in both groups. Heart rate, respiratory rate, blood pressure were measured before surgery, immediately after placental delivery and within 1 and 2 hours after birth of baby. Laboratory analysis comprising hemoglobin, urine routine and microscopy, liver and renal function tests were done before and on the third day after birth.
Blood Loss was Measured as
The quantity of blood loss (ml) intra operatively = (weight of used sponges during operation - weight of sponges prior to surgery) + volume of blood sucked in suction container after placental delivery.
In addition, pads used after completion of caesarean section up to 2 hours postpartum were separately weighed to assess the blood loss postoperatively. However, amniotic fluid and the amount of blood loss before placental delivery were not included in measuring blood loss.
Quantitative outcomes were summarized with mean and standard deviation. Categorical outcomes were summarized with percentages. For quantitative outcomes, t-test was used to test for difference in the two groups. For categorical outcomes, chi square and odds ratio with 95% confidence interval were used as applicable. A P-value of < 0.05 was taken as significant.
| Results|| |
The patients' characteristics in two groups were similar with no statistical significant difference [Table 1].
There was no significant difference in regard to obstetrical complications and indications of LSCS [Table 2]. All LSCS were done under spinal anesthesia and duration of surgery was 43.5 minutes in study group and 44.64 minutes in control groups which was statistically not significant. Elective and emergency caesarean sections were done in 50 patients each.
Hemoglobin decreased slightly after birth in both the groups, though not statistically significant [Table 3] and [Table 4]. No statistical significant difference has been observed in urine analysis, liver and renal function tests between two groups. There was no episode of thrombosis in the study.
Heart rates, respiratory rates and blood pressures were comparable in the two groups [Table 5].
Significant difference in the quantity of the blood loss from time of placental delivery to 2 hours postpartum was noticed. There was also statistically significant difference in quantity of blood loss from end of LSCS to 2 hours postpartum. However, no significant difference in quantity of blood loss from time of placental delivery to end of LSCS was observed [Table 6] and [Table 7].
| Discussion|| |
PPH is commonly defined as blood loss of ≥500 ml after vaginal delivery of a baby, or ≥1000 ml after caesarean section. However, these thresholds do not take into account pre-existing health status, and blood loss of as little as 200-300 ml can be life threatening for a woman with severe anemia or cardiac disease. 
There is a global commitment to the Millennium Development Goal (MDG) of reducing maternal deaths by three quarters by the year 2015, a commitment that requires a reduction of the maternal mortality ratio by 5.5% each year. Because maternal hemorrhage accounts for over a quarter of deaths, an effective treatment for PPH would contribute importantly to MDG of reducing maternal mortality. 
The WOMAN Trial (World Maternal Antifibrinolytic Trial) aims to determine the effect of early administration of TXA on mortality, hysterectomy and other morbidities (surgical interventions, blood transfusion, risk of non-fatal vascular events) in women with clinically diagnosed postpartum hemorrhage. The use of health services and safety, especially thromboembolic effect on breastfed babies will also be assessed. The trial will be large, pragmatic, randomized, double blind, placebo controlled trial among 15,000 women with a clinical diagnosis of postpartum hemorrhage. 
Continuous and constant efforts are made to unearth measures which will help in reducing bleeding following delivery whether by caesarean section or vaginal route. TXA which is known to help reduce surgical bleeding has been subject of many studies related to loss of blood following caesarean section. TXA achieves this by its antifibrinolytic effect by preventing binding of plasminogen and plasmin to the fibrin substrate. TXA also inhibits the conversion of plasminogen to plasmin by plasminogen activators. 
Fibrinogen and fibrin are rapidly degraded during placental delivery whereas plasminogen activators and fibrin degradation products increase due to activation of the fibrinolytic system.
The side effects described with the use of TXA include gastrointestinal symptoms such as diarrhea, nausea and vomiting that occur in about 10% of patients. Rare complications include hypotension, thrombosis, blurred vision, renal cortical necrosis and retinal artery obstruction.  No side effects were observed in our study.
A randomized case controlled prospective study was conducted on 100 women undergoing LSCS. TXA significantly reduced the quantity of blood loss from the end of LSCS to 2 hours postpartum which was 86.5 ml in the study group versus 142.70 ml in the control group (<0.001).  Similar findings have been observed in the present study.
TXA significantly reduced the blood loss from the end of caesarean section to 2 hours postpartum; 28.02 +/- 5.53 ml in the tranexamic group versus 37.12 +/- 8.97 ml in the control group (P = 0.000). Hemoglobin 24 hours after caesarean section was significantly greater in the tranexamic group than the control group (12.57 ± 1.33 in the tranexamic group and 11.74 ± 1.14 in the control group, P = 0.002). No complications or side effects were reported in either group.  In our study results are consistent with their findings, except that in our study, drop in hemoglobin concentration was statistically insignificant in two groups.
Ferrer et al. identified three randomized controlled trials involving 461 participants. Out of the three trials two were those who had caesarean section delivery , and one who had spontaneous vaginal delivery. 
Combining the results of the three trials, use of TXA significantly reduced mean blood loss by 92 ml (95% CI 76 to 109) compared to no treatment. There were no mortality and no thrombotic event was reported. The most frequently reported adverse effect of TXA was nausea although the increase was easily compatible with the play of chance (RR 4.63, 95% CI 0.23 to 95.14). 
Trials of the use of TXA for the prevention of obstetric hemorrhage used TXA at a dose of 1 gram without major complications.  In the emergency situation, the administration of a fixed dose is more practicable since weighing women with PPH would be difficult. Therefore, a fixed dose of 1 gram of TXA initially followed by 1 gram if bleeding continues, which is within the dose range which has been shown to inhibit fibrinolysis and provide haemostatic benefit, was selected for the WOMAN trial.  The same dosage has been used in our study.
A systemic review and cumulative meta-analysis of 129 trials totaling 10,488 patients carried out between 1972 and 2011 was done which estimated the effect of TXA on surgical bleeding.  This analysis revealed that TXA reduces blood transfusion in surgical patients. Although this evidence is available for over a decade, yet the effect on thromboembolic events and mortality remains uncertain which requires a large pragmatic clinical trial of TXA in a heterogeneous group of surgical patients. 
Therapeutic impact of the antifibrinolytic TXA has been a subject of another study called Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage (CRASH-2) study which demonstrated that TXA safely reduces risk of death in bleeding trauma patients. 
A small sample size and duration of study period are limitations of this study which is undertaken to draw attention to the need of undertaking multicentre randomized controlled trials to study its effect on thromboembolic events.
| Conclusion|| |
A safe dose of TXA plays an effective role in reducing the blood loss during lower segment caesarean section without causing complications. Therefore, this drug can be used effectively in reducing maternal morbidity and mortality during LSCS and is devoid of any side effects. However, its effect on thromboembolic events remains uncertain.
| Acknowledgement|| |
The above study was approved and sponsored by Indian Council of Medical Research as a part of short-term student's research project.
| References|| |
Tarabrin O, Kaminskiy V, Galich S, Tkachenko R, Gulyaev A, Shcherbakov S, et al. Efficacy of tranexamic acid in decreasing blood loss during cesarean section. Crit Care 2012;16(Suppl 1):439.
Kambo I, Bedi N, Dhillon BS, Saxena NC. A critical appraisal of cesarean section rates at teaching hospitals in India. Int J Gynaecol Obstet 2002;79:151-8.
Gohel M, Patel P, Gupta A, Desai P. Efficacy of tranexamic acid in decreasing blood loss during and after cesarean section: A randomised case controlled prospective study. J Obstet Gynecol India 2007;57:227-30.
Katsaros D, Petricevic M, Snow NJ,Woodhall DD,Van Bergen R. Tranexamic acid reduces postbypass blood use: A double-blinded, prospective, randomized study of 210 patients. Ann Thorac Surg 1996;61:1131-5.
Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. Military application of tranexamic acid in trauma emergency resuscitation (MATTERs) study. Arch Surg 2012;147:113-9.
Lalonde A, Daviss BA, Acosta A, Herschderfer K. Postpartum haemorrhage today: ICM/FIGO inititative 2004-2006. Int J Gynaecol Obstet 2006;94:243-53.
Shakur H, Elbourne D, Gülmezoglu M, Alfirevic Z, Ronsmans C, Allen E, et al. The WOMAN Trail (World Maternal Antifibrinolytic Trial): Tranexamic acid for the treatment of postpartum haemorrhage: An international randomised, double blind placebo controlled trial. Trials 2010;11:40.
Hoylaerts M, Lijnen HR, Collen D. Studies on the mechanism of the antifibrinolytic action of tranexamic acid. Biochim Biophys Acta 1981;673:75-85.
Astedt B. Clinical pharmacology of tranexamic acid. Scand J Gastroenterol Suppl1987;137:22-5.
Rashmi PS, Sudha TR, Prema P, Patil R, Vijaynath V. Role of tranexamic acid in reducing blood loss during and after cesarean section: A randomized case control prospective study. J Med Res Pract 2012;1.
Gai MY, Wu LF, Su QF, Tatsumoto K. Clinical observation of blood loss reduced by tranexamic acid during and after caesarian section: A multi-centre, randomized trial. Eur J Obstet Gynecol Reprod Biol 2004;112:154-7.
Yang H, Zheng S, Shi C. Clinical study on the efficacy of tranexamic acid in reducing postpartum blood loss: A randomized, comparative, multicenter trial. Zhonghua Fu Chan Ke Za Zhi 2001;36:590-2.
Ferrer P, Roberts I, Sydenham E, Blackhall K, Shakur H. Anti-fibrinolytic agents in post partum haemorrhage: A systematic review. BMC Pregnancy Childbirth 2009;9:29.
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.
Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, et al.; CRASH-2 trial collaborators. 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;376:23-32.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]