|Year : 2020 | Volume
| Issue : 4 | Page : 1270-1275
Effect of tranexamic acid in reducing blood loss during and after cesarean delivery
Zakaria F Sanad1, Hamed E Ellakwa1, Alaa M Gomaa1, Haitham A Hamza1, Haitham H Elsalamony2
1 Department of Obstetrics and Gynecology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Obstetrics and Gynecology, Alexandria Specialized Medical Center, Alexandria, Egypt
|Date of Submission||04-Apr-2020|
|Date of Decision||17-May-2020|
|Date of Acceptance||31-May-2020|
|Date of Web Publication||24-Dec-2020|
Haitham H Elsalamony
MBBCh, El Montazah, Alexandria
Source of Support: None, Conflict of Interest: None
The aim was to evaluate the effect of tranexamic acid (TA) in reducing blood loss during and after elective cesarean delivery (CS).
Postpartum hemorrhage is an obstetrical emergency that can follow delivery. It is a major cause of maternal sickness and maternal death.
Patients and methods
In all, 74 full-term pregnant primigravida with singleton pregnancy aged between 20 and 35 years, scheduled for elective CS were enrolled at a prospective study. The patients were divided into two groups. Group I: patients received a bolus injection of 1 g of intravenous TA diluted in 20 ml of 5% dextrose solution slowly over 5 min at 10 min before skin incision. Oxytocin 10 units in 500 ml normal saline (9% saline) intravenous drip (8 ml/min) were administrated after fetal delivery. Group II: no TA was given; oxytocin was administered as in group I. Preoperatively, complete blood picture and coagulation profile were done.
Hemoglobin and hematocrit levels decreased significantly in group II than in group I (P = 0.007; 0.005) consecutively. On comparing the two studied groups, there was a significant decrease in the amount of blood loss in group I than in group II (P = 0.001). More cases in group II than in the TA group required further ecbolic treatment during the postoperative period (P = 0.018).
A safe dose of TA plays an effective role in reducing blood loss during lower segment CS without causing complications.
Keywords: cesarean, delivery, hemorrhage, postpartum, tranexamic acid
|How to cite this article:|
Sanad ZF, Ellakwa HE, Gomaa AM, Hamza HA, Elsalamony HH. Effect of tranexamic acid in reducing blood loss during and after cesarean delivery. Menoufia Med J 2020;33:1270-5
|How to cite this URL:|
Sanad ZF, Ellakwa HE, Gomaa AM, Hamza HA, Elsalamony HH. Effect of tranexamic acid in reducing blood loss during and after cesarean delivery. Menoufia Med J [serial online] 2020 [cited 2021 Jun 24];33:1270-5. Available from: http://www.mmj.eg.net/text.asp?2020/33/4/1270/304481
| Introduction|| |
Blood loss during vaginal or cesarean delivery is always of prime concern. Despite significant improvement in obstetric care 125 000 women die from obstetric hemorrhage every year in the world. The lower segment cesarean delivery is an established procedure. It is a transverse incision on the lower uterine segment which is easier to repair and heal well. It is important to take convenient steps to decrease the amount of bleeding during and after cesarean delivery. Cesarean section (CS) rates have increased to as high as 25%–30% in many areas of the world. In spite of all measures to prevent blood loss during and after CS, postpartum hemorrhage (PPH) continues to be the most common complication seen in 20% of the cases, leading to increased maternal morbidity and mortality. Intravenous tranexamic acid (TA) has been routinely used for many years to decrease blood loss during and after surgical interventions 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 hemorrhage and incidence of blood transfusion in these surgeries. Use of TA has been a subject of intense debate in combat situations. Findings from MATTERs study reveal that the use of TA in conjunction with a blood component-based resuscitation following combat injury results in improved measures of coagulation defects and survival. This benefit was present in all who receive blood transfusions in this setting but was most prominent in those who needed massive transfusion. This study was done to evaluate the efficacy of TA in reducing blood loss after placental delivery following lower segment cesarean section (LSCS). In industrialized countries, PPH usually ranks in the top three causes of maternal sickness rates, along with embolism and hypertension. In the developing world, several countries have maternal mortality rates more than 1000 women per 100 000 live births, and WHO statistics suggest that 25% of maternal mortality are due to PPH, accounting for more than 100 000 maternal mortality per year. The definition of PPH is somewhat arbitrary and problematic. PPH is defined as blood loss of more than 500 ml following vaginal delivery or more than 1000 ml following CS. A loss of these amounts within 24 h of delivery is named early or primary PPH, whereas such losses are named late or secondary PPH if they occur 24 h after delivery. High-quality evidence suggests that active management of the third stage of labor decrease the incidence and severity of PPH. Active management consists of first, uterotonic administration immediately upon delivery of the baby; second, uterine message; and third, controlled cord traction with uterine countertraction (i.e. Brandt-Andrews maneuver). The aim of this study was to evaluate the effect of TA in reducing blood loss during and after an elective CS.
| Patients and methods|| |
After approval of Local Ethical Committee and with written informed consent, a prospective study was carried out in Menoufia University Hospital and The Governate Hospital for Birth (Dar Ismaael) on 74, healthy, full-term pregnant women aged between 20 and 35 years, scheduled for elective CS under spinal anesthesia from March 2018 to September 2019. The sample size and the number of the study groups were categorized after the recommendations of the Biostatistics Department in Faculty of Medicine, Menoufia University. The sample sizing assumes that the expected effect size is 2.75 in Hb drop between the group with TA and that without TA. To achieve 80% power to detect this difference with a significance level of 5%, it was estimated that 33 cases per group would be needed. With a withdrawal/nonevaluable subject rate of 10% a total of 37 per group participants were recruited leading to a total required sample size of 74 participants. Inclusion criteria: Pregnant at full term (=37 weeks gestation), 20–35 years, primigravida with singleton pregnancy. Exclusion criteria: Severe medical and surgical complications involving the heart, liver or the kidney; brain disease and blood disorders; hypersensitivity to TA; history of thromboembolic disorders; abnormal placenta (placenta previa and placental abruption), severe preeclampsia, multiple pregnancy, macrosomia, polyhydramnios, fibroid uterus, or anemia (hemoglobin < 10 g/dl). Patients were randomly categorized into two equal groups, Group I: patients received a bolus injection of 1 g of intravenous TA diluted in 20 ml of 5% dextrose solution slowly over 5 min at 10 min before skin incision. Oxytocin 10 units in 500 ml normal saline (9% saline) intravenous drip (8 ml/min/h) (1 g of intravenous TA diluted in 20 ml of 5% dextrose solution slowly over 5 min at 10 min before skin incision. Oxytocin 10 units in 500 ml normal saline (9% saline) intravenous drip) were administrated after fetal delivery. Group II: no TA was given; oxytocin was administered as in the study group. All patients were subjected to the following: Preoperative full history taking and clinical; general and obstetric examination, ultrasonography to define exclusion criteria, complete blood picture immediately before labor and coagulation profile including prothrombin time, partial thromboplastin time, and international normalized ratio. Anesthesia was spinal anesthesia and assessment of the blood loss intraoperatively by weighing an absorbing disposable sheet put under each case before and after being removed to assess the blood loss (the sheet was removed and weighed after the end of CS operation). However, amniotic fluid and the amount of blood loss before placental delivery were not included in measuring blood loss. The quantity of blood loss (ml) intraoperatively=(weight of used towels during operation–weight of towels prior to surgery)+volume of blood sucked in a suction container after placental delivery. Postoperative assessment of blood loss was done by the difference in hemoglobin and hematocrit values immediately preoperatively and 4 h postoperatively:
(estimated blood volume) = weight (kg) ×70 ml, where Hi is the initial hemoglobin and Hf is the final hemoglobin. Another sheet was put under each case and was weighed before being put and was removed and weighed 2 h after CS to assess the postoperative blood loss. Measured outcomes: the difference between preoperative, immediate postoperative, and 4 h postoperative hemoglobin and hematocrit values and the need for additional use of ecbolics.
Statistical analysis and data management
Data were fed to the computer and analyzed using International Business Machines Statistical Package for the Social Sciences (IBM SPSS) software package version 20.0. (IBM Corp., Armonk, New York, USA). The Kolmogorov–Smirnov test was used to verify the normality of distribution. Quantitative data were described using the range (minimum and maximum), mean, SD, and the median. Significance of the obtained results was judged at P value less than or equal to 0.05. The tests used were: Student's t-test for normally distributed quantitative variables, to compare between two studied groups and paired t-test for normally distributed quantitative variables, to compare between two periods. The sample size was 74 cases.
| Results|| |
In this study, there were no statistically significant differences between the two studied groups regarding maternal age and gestational age (P>0.05) [Table 1]. Hemoglobin and hematocrit levels before delivery in the two groups were matched without significant difference, while the level of h[Table 2] and hematocrit [Table 3] decreased significantly in group II than in group I (P = 0.007 and 0.005, respectively). The mean amount of blood loss in group I was 364.82 ± 33.16 ml, while in group II was 454.5 ± 40.23 ml. On comparing the two studied groups, it was found that there was a significant decrease in the amount of blood loss in group I than in group II (P = 0.001) [Table 4]. No cases needed blood transfusion. In this study, 17 cases of group I and 27 cases of group II needed additional ecbolics (such as syntocinon and misoprostol). More cases in group II than in the TA group required further ecbolic treatment during the postoperative period (P = 0.018) [Table 5]. Comparison between the two groups according to hemoglobin levels [Figure 1]. Comparison between the two groups according to blood loss [Figure 2].
|Table 1: Comparison between the two groups according to demographic data|
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|Table 2: Comparison between the two groups according to hemoglobin before and after delivery|
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|Table 3: Comparison between the two groups according to hematocrit before and after delivery|
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|Table 4: Comparison between the two groups according to blood loss during and after delivery|
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|Table 5: Comparison between the two groups according to the needed additional ecbolic|
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|Figure 1: Comparison between the two groups according to the level of hemoglobin.|
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| Discussion|| |
In this study, there were no statistically significant differences between the two studied groups regarding maternal age and gestational age. The PPH which is an early complication of cesarean delivery is defined as greater than 500 ml and greater than 1000 ml of blood loss after vaginal and cesarean delivery, respectively, with a hematocrit decrease greater than 10%. It is the main cause for maternal death rates in low-income countries. Further, it is the primary cause of nearly 1/4 of maternal death rates all over the world,. TA does its antifibrinolytic action by blocking the lysine binding locus of the plasminogen and plasmin molecules, thereby preventing the binding of plasminogen and plasmin to the fibrin substrate. TXA also prevents conversion of plasminogen to plasmin. After delivery of the baby, there is activation of fibrinolytic cascade transiently for 6 to 10 h. Hence, the role of an antifibrinolytic agent such as TXA is being evaluated for the prevention of PPH. The present study was carried out in Menoufia University Hospital and the Governate Hospital for Birth (Dar Ismael Hospital) on 74 healthy full-term pregnant women aged between 20 and 35 years, scheduled for elective cesarean delivery under spinal anesthesia. In this study, there were no statistically significant differences between the two studied groups regarding maternal age and gestational age. In our study of 74 patients, the cases were 37 patients who received a bolus injection of 1 g of intravenous TA diluted in 20 ml of 5% dextrose solution slowly over 5 min at 10 min before skin incision. Oxytocin 10 units in 500 ml normal saline (9% saline) intravenous drip (8 ml/min) were administrated after fetal delivery and 37 controls who had not received TA but received oxytocin 10 units as the first group. There is a statistically significant difference in the quantity of blood loss intraoperatively, that is, from the time of placental delivery to the end of CS with a mean blood loss of 293.6 ml in the study group vs 328.3 ml in the other group (P < 0.001). Our result of this study shows that TA significantly reduces bleeding from the end of CS to 2 h post-CS with a mean blood loss of 71.22 ml in the study group vs 126.2 ml in the control group (P < 0.001). The Sherafati et al. study included 108 primigravida who were randomized into two groups also showed that TA reduces the amount of blood loss from the end of LSCS to 2 h postpartum significantly: 42.75 ± 40.45 ml in the study group vs 73.98 ± 77.09 ml in the control group (P = 0.001). It showed reduced quantity of total blood from placental separation to 2 h postpartum significantly: 351.57 ± 148.20 ml in the study group and 439.36 ± 191.48 ml in the control group (P = 0.002). The study also proves significant decrease in the incidence of greater than 500 ml blood loss in the study group as compared with the control group (P = 0.029). Li et al. assessed the efficacy and safety of TA in reducing blood loss in patients undergoing cesarean delivery. Finally, 25 articles with 4747 participants were included. Our results indicated that TA resulted in a reduced intraoperative, postoperative, and total blood loss by a mean volume of 141.25 ml (P<0.00001), 36.42 ml (P<0.00001), and 154.25 ml (P<0.00001) in CS. In addition, TA could decrease the rate of PPH and severe PPH. The findings indicated that intravenous TA for patients undergoing cesarean delivery was effective and safe. Ali et al. proved the efficacy and safety of TA in reducing blood loss during cesarean delivery. A prospective randomized research was conducted on 90 primigravida who were divided into two groups who underwent cesarean delivery. The study group, 45 women, received TA immediately before CS, whereas the control group, 45 women, received placebo. The amount of blood loss was measured from the end of CS to 2 h postpartum and compared between the two groups. TA reduced the blood loss from the end of CS to 2 h postpartum significantly; 28.02 ± 5.53 ml in the tranexamic group vs 37.12 ± 8.97 ml in the control group (P = 0.000). Another study obtained similar results; TXA significantly reduced the amount of blood loss during cesarean delivery. There was significant reduction in blood loss measured from placental delivery till the end of cesarean delivery: 347.17 ml in the study group vs 517.72 ml in the control group (P < 0.001) Lakshmi and Abraham. In a study, the efficacy and safety of TA in reducing blood loss after placental separation following lower segment cesarean delivery was evaluated. They proved that a statistically significant difference in the amount of blood loss from the end of LSCS to 2 h postpartum Bhatia et al.. In addition, Chattopadhyay et al. found the efficacy and safety of TA in reducing blood loss during and after cesarean delivery. A prospective randomized, case–control study was conducted on 100 women who opt for cesarean delivery. Fifty of them were given TA immediately before cesarean delivery and compared with 50 others to whom TA was not given. Blood loss was measured up to 2 days. In this study, it was found that TA reduced the amount of blood loss from placental separation to 2 days postpartum: 990 ml in the study group vs 1004 ml in the control group. Therefore, TA significantly reduced the amount of blood loss during and after cesarean delivery. In this study, there was significant difference in post-CS hemoglobin levels between the two groups, the mean concentration being 10.0 g% in the study group vs 8.8 g% in the control group (P = 0.000). The difference between the preoperative and postoperative hemoglobin and hematocrit values was also significantly less in the study group than the control group (P = 0.000). Other hematologic and biochemical parameters did not have any significant difference in the two groups. These results were comparable with the study by Sherafati et al. and Pakniat et al.,. A study found that TXA significantly reduced the amount of blood loss during CS, the percentage of fall in hemoglobin before and after surgery, and the number of patients who had more than 10% decrease in hemoglobin. Of the patients 9.3% in study group and 39% in the control group had more than 10% fall in hemoglobin level (P < 0.01). Bhatia et al. found that there were statistically significant differences between the studied groups regarding hemoglobin and hematocrit 24 h after cesarean delivery. These results are consistent with the present study except that in our study the hemoglobin level was measured after 4 h and an additional dose of methylergometrine (0.2 mg IM) was given in this study after delivery of babies in both groups. Ali et al. found that hemoglobin 24 h after a cesarean delivery 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). In accordance with our results, other studies reported no complications or side effects were reported in either group. In this study, 17 cases of group I and 27 cases of group II needed additional ecbolics (as syntocinon and misoprostol). More patients in the control group than in the TA group required further ecbolic treatment during the postoperative period. TA could be used in women with a high risk of blood loss to decrease the need for blood transfusion or serious PPH. Furthermore, the drug decreases the use of ecbolic drugs during the postoperative period. Sentilhes et al. determine the efficacy and safety of TA in reducing blood loss during elective cesarean delivery. Furthermore, more women in the placebo group than in the TA group needed additional uterotonic agents [48 (14.5%) vs 28 (8.5%), respectively). TA significantly reduced bleeding during CS, the percentage of patients with blood loss greater than 1000 ml, and the need for additional uterotonic agents. Ifunanya et al. evaluated the efficacy of TXA in reducing blood loss when given before cesarean delivery. The number of cases who needed additional uterotonic agents was significantly lower in the TXA group than in controls. Pregnancy is a hypercoagulable state; hence, the risk of thrombotic events is more during pregnancy. Nevertheless, the use of this antifibrinolytic was not associated with any side effects or complications in the immediate postpartum period. Hence, TA can be used safely and effectively in individuals undergoing cesarean delivery.
| Conclusion|| |
Prophylactic TXA given before cesarean skin incision in women undergoing cesarean delivery significantly decreases blood loss, including PPH.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Muñoz M, Stensballe J, Ducloy-Bouthors AS, Bonnet MP, De Robertis E, Fornet I, et al
. Patient blood management in obstetrics: prevention and treatment of postpartum haemorrhage. A NATA consensus statement. Blood Transfus 2019; 17
Gupta M and Garg V. The rate and indications of caesarean section in a tertiary care hospital at Jaipur, India. Int J Reprod Contracept Obstet Gynecol 2017; 6
Spahn DR, Bouillon B, Cerny V, Cerny V, Duranteau J, Filipescuet D, et al
. The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition. Crit Care 2019; 23
Stokes MJ, Wilkinson JP. The causes of maternal mortality are changing and preventable. BJOG 2018; 125
Ouh YT, Lee KM, Ahn KH, Hong SC, Oh MJ, Kim HJ, et al
. Predicting peripartum blood transfusion: focusing on pre-pregnancy characteristics. BMC Pregnancy Childbirth 2019; 19
Wang Y, Liu S, He L. Prophylactic use of tranexamic acid reduces blood loss and transfusion requirements in patients undergoing cesarean section: a meta-analysis. J Obstet Gynaecol Res 2019; 45
Wudneh A, Dheresa M, Demena M. Active management of third stage of labour: practice and associated factors among obstetric care providers' at health facilities in Kambata-Tembaro Zone, Southern Ethiopia 2018. Int J Pregn Child Birth 2019; 5
Saccone G, Della Corte L, D'Alessandro P, Ardino B, Carbone L, Raffone A, et al
. Prophylactic use of tranexamic acid after vaginal delivery reduces the risk of primary postpartum hemorrhage. J Mater Fetal Neonat Med 2019; 31:1-9.
Sherafati G, Akhlaghi F, Mostafa K. Assessment of the effects of tranexamic acid (TXA) in reducing bleeding loss during and after cesarean section (CS). Adv Biores 2017; 8
Bhatia BK, Vachhani R, Ratnani R. Study the efficacy of tranexamic acid in reducing blood loss during LSCS. Int J Innov Res Med Sci 2018; 3:1831-to.
van der Vorm LN, Remijn JA, de Laat B, Huskens D. Effects of plasmin on Von Willebrand factor and platelets: a narrative review. TH Open 2018; 2
Li C, Gong Y, Dong L, Xie B, Dai Z. Is prophylactic tranexamic acid administration effective and safe for postpartum hemorrhage prevention: a systematic review and meta-analysis. Medicine (Baltimore) 2017; 96
Ali SA, Oof TF, Elmolla MF. Efficacy of intravenous tranexamic acid in reducing blood loss after elective cesarean section. Egypt J Hosp Med 2019; 74
Lakshmi SD and Abraham R. Role of prophylactic tranexamic acid in reducing blood loss during elective caesarean section: a randomized controlled study. J Clin Diagn Re 2016; 10
Bhatia SK and Deshpande H. Role of tranexamic acid in reducing blood loss during and after caesarean section. Med J Dr DY Patil Univ 2015; 8
Chattopadhyay S, Sarkar S, Chakrabarti S, Mandal MC. Effect of intravenous tranexamic acid administration on blood loss during and after elective caesarean delivery – A randomised placebo-controlled study. J Evol Med Dent Sci 2017; 6
Pakniat H, Chegini V, Shojaei A, Khezri MB, Ansari I. Comparison of the effect of intravenous tranexamic acid and sublingual misoprostol on reducing bleeding after cesarean section: a double-blind randomized clinical trial. J Obstet Gynecol India 2019; 69
Acharya S, Mishra S. Efficacy of tranexamic acid in reducing blood loss in cesarean section: a comparative study. J Lumbini Med Coll 2019; 7
Sentilhes L, Daniel V, Deneux-Tharaux C. TRAAP2-TRAnexamic acid for preventing postpartum hemorrhage after cesarean delivery: a multicenter randomized, doubleblind, placebo-controlled trial – a study protocol. BMC Preg Childbirth 2020; 20
Ifunanya NJ, Chukwu IC, Nobert OC, Blessing O, Chibuzor UD, Uchenna OV. Tranexamic acid vs placebo for prevention of primary postpartum haemorrhage among high risk women undergoing caesarean section in Abakaliki: a randomized controlled trial. Open J Obstet Gynecol 2019; 9
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]