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ORIGINAL ARTICLE
Year : 2019  |  Volume : 32  |  Issue : 2  |  Page : 465-469

Misoprostol and tranexamic acid role in reducing blood loss during the elective cesarean section


1 Department of Obstetrics and Gynecology, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt
2 Department of Obstetrics and Gynecology, Tala Hospital, Tala City, Egypt

Date of Submission04-Jan-2018
Date of Acceptance03-Mar-2018
Date of Web Publication25-Jun-2019

Correspondence Address:
Yehia Z El-Sayd Ghnnam
Tala City 8001, Menoufia Governorate
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_916_17

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  Abstract 


Objective
To compare the efficacy of using misoprostol alone or in combination with tranexamic acid (TA) in reducing blood loss during elective cesarean section (CS).
Background
Normal blood loss during labor is ∼300–400 ml. Blood loss more than 500 ml following vaginal birth or greater than 1000 ml following CS means postpartum hemorrhage.
Patients and methods
A prospective randomized comparative clinical study was conducted on 150 patients who were divided into two groups: group A (75 patients) received misoprostal 600 mcg rectally before the incision, and group B (75 patients) received misoprostal 600 mcg rectally and 1-g TA slowly intravenously 10 min before the incision. Full medical history, physical examination (general condition and vital signs), prothrombin time, liver and kidney functions, and blood loss volume were recorded.
Results
Mean age of the studied patients was 28.32 ± 4.65 years in group A and 27.81 ± 5.07 years in group B. Moreover, there was a statistically significant difference between groups regarding hemoglobin postoperatively (P = 0.038), hematocrit postoperatively (P = 0.033), systolic (P = 0.043) and diastolic (P = 0.037) blood pressures 2 h postoperatively, heart rate 2 h postoperatively (P = 0.045), blood loss in the first (P < 0.001) and second periods (P = 0.019), and total blood loss (P < 0.001), with a difference of 146.15 ml (22.6%) less blood loss observed in group B than group A.
Conclusion
The use of TA before CS is significantly effective in reducing blood loss during cesarean birth, with no observed maternal or neonatal adverse effects (in addition to its low cost). Misoprostol in combination with TA is the most effective treatment in decreasing the amount of blood loss during CS.

Keywords: blood pressure, cesarean section, misoprostol, postpartum hemorrhage, tranexamic acid


How to cite this article:
El-Sttar MM, El-Gayed AM, Dawood RM, El-Sayd Ghnnam YZ. Misoprostol and tranexamic acid role in reducing blood loss during the elective cesarean section. Menoufia Med J 2019;32:465-9

How to cite this URL:
El-Sttar MM, El-Gayed AM, Dawood RM, El-Sayd Ghnnam YZ. Misoprostol and tranexamic acid role in reducing blood loss during the elective cesarean section. Menoufia Med J [serial online] 2019 [cited 2019 Sep 20];32:465-9. Available from: http://www.mmj.eg.net/text.asp?2019/32/2/465/260943




  Introduction Top


Cesarean section (CS) rate has increased to as high as 25–30% in many areas of the world. Delivery by CS can cause more complications than normal vaginal delivery, and one of its common complications is postpartum bleeding, which can be life threatening. To reduce maternal mortality and morbidity caused by bleeding, it is important to reduce the extent of bleeding during and after CS[1]. Normal blood loss during labor is ∼300–400 ml, and blood loss of more than 500 ml following vaginal birth or greater than 1000 ml following CS means postpartum hemorrhage (PPH)[2]. To control bleeding after CS, some medications such as oxytocin, prostaglandins (E1, E2, and F2α), and methylergonovine have been used[3]. Tranexamic acid (TA) is a synthetic derivative of amino acid lysine that exerts its antifibrinolytic effect through the reversible blockade of the lysine-binding sites of plasminogen molecule[4]. It works by helping to prevent the breakdown of fibrin and maintenance of blood clots. It has been routinely used for many years to reduce hemorrhage during and after surgical procedures such as coronary artery bypass, prostatectomy, and knee arthroplasty. It has been shown to be very useful for reducing blood loss and blood transfusion[5]. There are some reports on preventing blood loss in many gynecological diseases such as menorrhagia and CS with TA[6]. Prostaglandins are the natural stimulant of the myometrium activity and have proven to be effective in induction of labor and abortion. They work by their ability to displace calcium through the cell membrane, mediated by their binding to their cell membrane receptors that operate via G proteins, which subsequently activate or inhibit adenyl cyclase, or stimulate phospholipase C[7]. Obstetrician should always consider postoperative bleeding (postpartum bleeding) that may follow CS. Many researches discussed the effects of combination of the medications in decreasing blood loss in CS. Therefore, it sought to evaluate the effects of type of medications on blood loss during and after CS by comparing the changes of hemoglobin (Hb) and hematocrit (HCT) at CS[8]. The aim of this study was to compare the efficacy of using misoprostol alone or in combination with TA in reducing blood loss during the elective CS.


  Patients and Methods Top


A prospective randomized comparative study was carried out on 150 patients who attended Obstetrics and Gynecology Outpatient Clinic at Menoufia University Hospital and Tala Central Hospital during the period from October 2016 to March 2017.

Ethical consideration

The study started after approval of protocol by the Ethical Committee of Faculty of Medicine, Menoufia University. For each patient included in the study, the following measures were taken: informed consent was taken from the patients after explanation of the importance of the study to patients to become more interested and cooperative with the procedures, the confidentiality of the patient's data was guaranteed, the patients had the right to refuse participation in this study and to end the meeting at any time they want without giving any reasons, and all samples were discarded after finishing the study and were not used by any means in further research or experiments.

Sampling methods

The randomization list was concealed and accessed by sequentially numbered, opaque, sealed envelopes immediately before the intervention. According to the randomization plan, a plan of interventions was sealed in closed envelops and numbered. Other than the investigator, two independent doctors performed the packing, sealing, and numbering. Surgeons and investigators were not aware whether patient received TA. Randomization coding tables were concealed from investigators till the end of the study. The investigator supervised application of the medication from the package carrying the number matching with the patient's entry number; the main investigators kept the sealed envelopes with the number of order till the end of the study. The medications were strictly allocated in the order of the numbers, according to the randomization plan; subjects withdrawn from the study were not substituted, and the next patient included in the study received the next number.

Subjects included in the study were randomly divided into two equal groups as follow:

  1. Group A included 75 patients who received misoprostal 600 mcg rectally before the incision
  2. Group B included 75 patients who received misoprostal 600 mcg rectally and 1 g TA slowly intravenously 10 min before the incision.


Inclusion criteria

The inclusion criteria were as follows: elective CS, full-term birth (38–40 weeks), singleton pregnancy, and no medical disorders.

Exclusion criteria

The exclusion criteria included severe medical and surgical disorders; thyroid dysfunction, which was excluded by routine thyroid function test (free T3, free T4, and thyroid stimulating hormone (TSH), all of them should be within normal limits); bleeding tendency, for example, disseminated intravascular coagulopathy, which was excluded by platelet count, coagulation time, bleeding time, prothrombin time, partial thromboplastin time, and thrombin time (all should be within normal); acute liver or kidney diseases; blood disorders, such as anemia; allergy to TA; allergy to misoprostol; contraindication to misoprostol, for example, bronchial asthma and heart disease; history of thromboembolic disorders; risk factors for PPH, such as polyhydramnios, fetal macrosomia, antepartum hemorrhage, or prolonged obstructed labor; abnormal placenta such as placenta previa and placenta abruptia; pregnancy complications such as severe pre-eclampsia; multiple pregnancies; those requiring blood transfusion; and patients who refused spinal anesthesia.

All pregnant women who fulfill the eligibility criteria were subjected to the following:

Preoperative management

  1. Full medical history taking, including present and past history
  2. Physical examination, including general condition and vital signs such as heart rate (HR), blood pressure, and respiratory rate, which will be checked before the operation
  3. Prothrombin time, complete blood count, and urine analysis
  4. Liver and kidney functions
  5. Estimation of the weight of the operative towels before the operation
  6. A written consent was taken after explaining the trial to each patient.


Intraoperative management

  1. Overall, 75 patients received misoprostal 600 mcg rectally before the incision and 75 patients received misoprostal 600 mcg rectally and 1-g TA slowly intravenously over 5–10 min before the incision. The two groups received 10 IU oxytocin during the CS.


Postoperative management

  1. Vital signs such as HR, blood pressure, and respiratory rate were checked after the operation. The volume of postpartum blood loss was measured by weighting soaked towels after the operation and volume of blood aspirated by suction apparatus with graduated bottle
  2. Blood loss volume=wet weight of the patient pad or tampon–dry weight of the pad or tampon/1.05[9]
  3. Hb and HCT values were compared with the previous level. The change in Hb levels calculated by comparing the 24 h postoperative to preoperative Hb level. If Hb reduction was 1 g/dl, it considered as massive blood loss. Blood loss was collected and measured first from the time of placental delivery till the end of lower segment cesarean section (LSCS) and later from the end of LSCS to 2-h postpartum period.


Statistical analysis

Analysis of data was done by DELL computer using statistical package for the social sciences (SPSS), version 22 (SPSS Inc., Chicago, Illinois, USA) as follows: description of quantitative variables as mean ± SD or median and range as appropriate. Description of qualitative variables was done as number or frequency and percentage. Student's t-test, independent t-test, paired t-test, and Fisher exact test were used for analysis. A value of P less than 0.05 was indicated statistically significant.


  Results Top


Mean age (year) of the studied patients was 28.32 ± 4.65 years in group A, and 27.81 ± 5.07 in group B, whereas mean BMI and gestational age were 29.55 ± 3.08 weeks and 29.24 ± 3.00 kg/m2, respectively, in group A and 38.22 ± 1.10 weeks and 38.19 ± 0.7, respectively, in group B. Moreover, there was no statistically significant difference (P > 0.05) between the studied groups regarding demographic data, parity, and Hb (g/dl) preoperatively. On the contrary, there was statistically significant difference between the groups regarding Hb (g/dl) postoperatively and HCT% postoperatively. Group B recorded higher values of Hb (g/dl) postoperatively (11.44 ± 1.24 vs. 9.55 ± 1.18) and HCT% postoperatively (35.47 ± 3.74 vs. 30.91 ± 3.97) compared with group A [Table 1].
Table 1: Comparison between groups A and B regarding demographic data, hemoglobin, hematocrit, and parity

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There was a statistically significant difference between the studied groups regarding systolic (P = 0.043) and diastolic (P = 0.037) blood pressures 2 h postoperatively and HR 2 h postoperatively (P = 0.045). However, there was a highly significantly difference between the studied groups regarding blood loss in the first (P < 0.001) and second periods (P = 0.19) and the total blood loss (P < 0.001), with as much as 146.15 ml (22.6%) less blood loss in group B compared with group A. On the contrary, there was no significant difference between the studied groups regarding systolic (P = 0.885) and diastolic (P = 0.625) blood pressure preoperatively, as well as HR (beats/min) preoperatively [Table 2].
Table 2: Comparison between groups A and B regarding blood pressure and heart rate as well as blood loss

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There was no statistically significant difference between the two studied groups regarding intraoperative events [Table 3].
Table 3: Comparison between groups A and B regarding intraoperative events

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  Discussion Top


In our study, there was a statistically significant difference between the two groups regarding the vital data immediately after placental delivery and 2 h postoperatively. Systolic and diastolic blood pressures 2 h postoperatively were higher in group B than group A, and HR 2 h postoperatively was significantly higher in group A than group B. Our results agree with Shakur et al.[10], who found that there was a statistically significant difference between TA and placebo groups regarding any vascular occlusive event, myocardial infarction, systolic blood pressure (mmHg), respiratory rate (/min), and HR (beats/min). However, our results disagree with the study done by Gohel et al.[6] and Sekhavat et al.[11], who found there was no statistically significant difference in the HRs, respiratory rates, and blood pressures in the two groups.

The current study showed that postoperative Hb and HCT were significantly higher in group B than group A. Reduction in Hb and HCT was significantly less in group B than group A. These results agree with Gai et al.[2], Sekhavat et al.[11], and Gohel et al.[6], which was mostly because of the significant reduction of the quantity of blood from the end of CS to 2 h postpartum period. Moreover, Abdel-Aleem et al.[12] found that the mean decreases in HCT and Hb levels were statistically significant lower in the TA group than in the control group. This observation is in accordance with that of Gungorduk et al.[4], where the frequency of blood loss of more than 1000 ml was higher in the placebo group than in the TA group. Our results revealed that addition of TA significantly reduced bleeding during and after CS. The total blood loss from placental delivery till 2 h postoperatively was significantly less in group B (501.28 ± 119.2 ml) than group A (647.43 ± 178.77 ml), by efficacy of difference 146.15 ml (22.6%) less than group A. These results agreed with Gungorduk et al.[4], who demonstrated that the mean calculated blood loss was significantly lower in the TA group than in the control group, and the mean measured blood loss from placental delivery to 2 h postpartum in the intervention group was less than in the control group.

In our study, total blood loss from placental delivery until end of CS was significantly lower in group B (386.55 ± 104.98 ml) than group A (507.76 ± 152.14 ml). Most studies have been conducted to assess the effect of TA on reducing blood loss during CS. Several studies, totaling 2267 women, demonstrated a reduction in blood loss when using TA. The mean blood loss in the period between the end of CS and 2 h postpartum was significantly lower in the intervention (TA) group than in the control group[6],[9],[13]. However, the mean of blood loss in the period from placental delivery to the end of the CS did not differ between the TA and control groups. Movafegh et al.[14] and Gungorduk et al.[4] reported that the mean blood loss during the intrapartum period in the intervention group (TA) was also significantly less than that in the control group. These results are also supported by our study. Heesen et al.[15] identified seven trials in which six reported the usage of TA in CS and one reported the usage of TA in venereal disease (VD). Their results showed TA usage rendered a reduced blood loss by a mean volume of 140.29 ml as compared with control group. However, their study did not consider the influence of model of delivery, which might introduce bias. Additionally, Sahhaf et al.[16] found no adverse effects such as nausea, vomiting, diarrhea, or hypotension owing to Tranexamic acid (TXA) administration in group receiving TA. No adverse effects were detected owing to rectal misoprostol administration in group receiving misoprostol, except one case of disseminated intravascular coagulation, which was owing to pre-eclampsia. Furthermore, Peitsidis and Kadir[17] found significantly less bleeding from the end of CS to 2-h postpartum period in preoperative TA-treated group. Bleeding from the placental delivery to 2 h postpartum period was also found to be less in the study group. So TA was found to beneficial not only to prevent PPH, but also for its management. Our results disagreed with Gai et al.[2], who found no significant difference between the two groups regarding the quantity of blood from the time of placental delivery to the end of CS. These results may be due to blood loss from placental delivery till 2 h postoperatively. However, Gai et al.[2] reported only blood loss greater than 400 ml and included only single primigravida. The reasons behind a choice of an outcome such as blood loss greater than 400 ml are not clear.

Possible bias in our study might result from exclusion of the cases with higher risks for PPH, but they were excluded from other studies as well. Our study included elective CS only, whereas emergency CS were excluded, which might affect our results, which agreed with Gai et al.[2], Gohel et al.[6], and Sekhavat et al.[11].


  Conclusion Top


The use of TA before CS is significantly effective in reducing blood loss during cesarean birth with no observed maternal or neonatal adverse effects (in addition to its low cost). Misoprostol in combination with tranexamic acid is the most effective treatment in decreasing the amount of blood loss during a CS. Further large studies are needed to establish the recommended dose of misoprostol to be used for decreasing intraoperative blood loss and prevention of PPH.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Declercq E, Barger M, Cabral HJ, Evans SR, Kotelchuck M, Simon C, et al. Maternal outcomes associated with planned primary cesarean births compared with planned vaginal births. Obstet Gynecol 2007; 109:669–677.  Back to cited text no. 1
    
2.
Gai MY, Wu LF, Su QF, Tatsumoto K. Clinical observation of blood loss reduced by tranexamic acid during and after caesarean section: a multicenter, randomized trial. Eur J Obstet Gynecol Reprod Biol 2004; 112:154–157.  Back to cited text no. 2
    
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Hofmeyr GJ, Walraven G, Gulzemoglu AM, Maholwana B, Alfirevic Z, Villar J, et al. Misoprostol to treat postpartum hemorrhage: a systematic review. BJOG 2005; 112:547–553.  Back to cited text no. 3
    
4.
Gungorduk K, Yıldırım G, Asıcıoglu O, Gungorduk OC, Sudolmus S, Ark C. Efficacy of intravenous tranexamic acid in reducing blood loss after elective cesarean section: a prospective, randomized, double-blind, placebo-controlled study. Am J Perinatol 2013; 28:233–240.  Back to cited text no. 4
    
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Zang JK, Klein HG, Fraser W, Shu X, Tian X, Yang H, et al. blood cell transfusion in the treatment and management of anemia: the search for the elusive transfusion trigger. Vox Sang 2012; 98:2–11.  Back to cited text no. 5
    
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Gohel M, Patel P, Gupta A, Pankaj D. Efficacy of tranexamic acid in decreasing blood loss during and after cesarean section: a randomized case controlled prospective study. Obstet Gynecol India 2007; 57:228–230.  Back to cited text no. 6
    
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Larsson C, Saltvedt S, Wiklund I, Pahlen S, Andolf E. Estimation of blood loss after cesarean section and vaginal delivery has low validity with a tendency to exaggeration. Acta Obstet Gynecol Scand 2006; 85:1448-52.  Back to cited text no. 7
    
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Larsson C, Saltvedt S, Wiklund I, Pahlen S, Andolf E. Estimation of blood loss after cesarean section and vaginal delivery has low validity with a tendency to exaggeration. Acta Obstet Gynaecol Scand 2006; 85:1448–1452.  Back to cited text no. 8
    
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Senturk M, Cakmak Y, Yildiz G, Yildiz P. Tranexamic acid for cesarean section: a double-blind, placebo-controlled, randomized clinical trial. Arch Obstet Gynecol 2013; 287:641–645.  Back to cited text no. 9
    
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Shakur H, Elbourne D, Gülmezoglu M, Alfirevic Z, Ronsmans C, Allen E, et al. The WOMAN Trial (World Maternal Antifibrinolytic Trial): tranexamic acid for the treatment of postpartum haemorrhage: an international randomised, double blind placebo controlled trial. Trials 2010; 11:40.  Back to cited text no. 10
    
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Sekhavat L, Tabatabaii A, Dalili M, Farajkhoda T, Tafti AD. Efficacy of tranexamic acid in reducing blood loss after cesarean section. J Matern Fetal Neonatal Med 2008; 22:72–75.  Back to cited text no. 11
    
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Abdel-Aleem H, Alhusaini TK, Abdel-Aleem MA, Menoufy M, Gülmezoglu AM. Effectiveness of tranexamic acid on blood loss in patients undergoing elective cesarean section: randomized clinical trial. J Matern Fetal Neonatal Med 2013; 26:1705–1709.  Back to cited text no. 12
    
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Xu J, Gao W, Ju Y. Tranexamic acid for the prevention of postpartum hemorrhage after cesarean section: a double-blind randomization trial. Arch Gynaecol Obstet 2013; 415:124–127.  Back to cited text no. 13
    
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Movafegh A, Eslamian L, Dorabadi A. Effect of intravenous tranexamic acid administration on blood loss during and after cesarean delivery. Int J Gynaecol Obstet 2011; 115:224–226.  Back to cited text no. 14
    
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Heesen M, Bohmer J, Klohr S, Rossaint R, van de Velde M, Dudenhausen JW. Prophylactic tranexamic acid in parturient at low risk for post-partum haemorrhage: systematic review and meta-analysis. Acta Anaesthesiol Scand 2014; 58:1075–1085.  Back to cited text no. 15
    
16.
Sahhaf F, Abbasalizadeh S, Ghojazadeh M, Velayati A, Khandanloo R, Saleh P, et al. Comparison effect of intravenous tranexamic acid and misoprostol for postpartum haemorrhage. Niger Med J 2014; 55:348–353.  Back to cited text no. 16
    
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Peitsidis P, Kadir RA. Antifibrinolytic therapy with tranexamic acid in pregnancy and postpartum. Expert Opin Pharmacother 2011; 12:503–516.  Back to cited text no. 17
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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