Shadman Noshin
Mini-CAT
Clinical Question: As in the past, please briefly outline the scenario and state your clinical question as concisely and specifically as possible
27 y/o female G2P1001, 38 weeks 2 days pregnant, with a significant past medical history of postpartum hemorrhage after her first delivery and a history of GDM is admitted to the Labor and Delivery department for induction of labor. Since the patient has a history of postpartum hemorrhage, she is at high risk for postpartum bleeding this time again. So, the attending is planning to give the patient tranexamic acid to prevent postpartum hemorrhage.
PICO Question:
Identify the PICO elements – this should be a revision of whichever PICO you have already begun in a previous week
Is tranexamic acid (TA) effective enough to prevent post-partum hemorrhage in pregnant patients who are at high risk of post-partum hemorrhage?
| P | I | C | O |
| Pregnant women | Tranexamic acid | No medication | Reduced post-partum hemorrhage |
| Pregnant females at high risk of post-partum hemorrhage | TXA | No prophylaxis | Decreased post-partum bleeding |
| Pregnant females at high risk of PPH | Cyklokapron | ||
| Lysteda |
Search Strategy:
Outline the terms used, databases or other tools used, how many articles returned, and how you selected the final articles to base your CAT on. This will likewise be a revision and refinement of what you have already done.
PubMed
Tranexamic acid for high risk postpartum hemorrhage (No filter) → 18 results
Tranexamic acid postpartum hemorrhage (No filter) → 154 results
Tranexamic acid post-partum hemorrhage (Filters: best match, published within last 5 years and humans) → 68 results
Tranexamic acid prevent postpartum hemorrhage (No filter) → 17 results
Prophylactic tranexamic acid postpartum hemorrhage (No filter) → 23 results
Prophylactic tranexamic acid postpartum hemorrhage (Filters: within last 10 years, human and best match) → 19 results
Cochrane Library
Tranexamic acid for high risk postpartum hemorrhage (No filters) → 2 results
Tranexamic acid postpartum hemorrhage (No filter) → 1 result
Tranexamic acid prevent postpartum hemorrhage (No filter) → 4 results
NEJM
Tranexamic acid prevent postpartum hemorrhage (No filter) → No result
Articles Chosen (3-5) for Inclusion (please copy and paste the abstract with link):
Please pay attention to whether the articles actually address your question and whether they are the highest level of evidence available. If you cannot find high quality articles, be prepared to explain the extensiveness of your search and why there aren’t any better sources available.
- Tranexamic Acid for Preventing Postpartum Haemorrhage.
Citation
Novikova, N., Hofmeyr, G.J., & Cluver, C. (2015). Tranexamic Acid for Preventing Postpartum Haemorrhage. The Cochrane Database of Systematic Reviews 16(6). https://www.ncbi.nlm.nih.gov/pubmed/26079202
Abstract
BACKGROUND:
Postpartum haemorrhage (PPH) is a common and potentially life-threatening complication of labour. Several options for preventing PPH are available, but further advances in this field are important, especially the identification of safe, easy to use and cost-effective regimens. Tranexamic acid (TA), which is an antifibrinolytic agent that is used widely to prevent and treat haemorrhage, merits evaluation to assess whether it meets these criteria.
OBJECTIVES:
To determine, from the best available evidence, whether TA is effective and safe for preventing PPH in comparison to placebo or no treatment (with or without uterotonic co-treatment), or to uterotonic agents.
SEARCH METHODS:
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (28 January 2015) and reference lists of retrieved studies.
SELECTION CRITERIA:
All published, unpublished and ongoing randomised controlled trials (RCTs) evaluating the use of TA alone or in addition to uterotonics in the third stage of labour or during caesarean section (CS) to prevent PPH.
DATA COLLECTION AND ANALYSIS:
Two review authors independently assessed for inclusion all the potential studies identified as a result of the search strategy. We entered the data into Review Manager software and checked for accuracy.
MAIN RESULTS:
Twelve trials involving 3285 healthy women at low risk of excessive bleeding undergoing elective CS (nine trials, 2453 participants) or spontaneous birth (three trials, 832 participants) satisfied inclusion criteria and contributed data to the analysis. All participants received routine prophylactic uterotonics in accordance with the local guideline in addition to TA or placebo or no intervention. Overall, included studies had moderate risk of bias for random sequence generation, allocation concealment, blinding, selective reporting and low risk of bias for incomplete data. The quality of evidence was also as assessed using GRADE.Blood loss greater than 400 mL or 500 mL, and more than 1000 mL was less common in women who received TA versus placebo or no intervention (risk ratio (RR) 0.52, 95% confidence interval (CI) 0.42 to 0.63, six trials, 1398 women; moderate quality evidence) and (RR 0.40, 95% CI 0.23 to 0.71, six trials, 2093 women; moderate quality evidence), respectively. TA was effective in decreasing the incidence of blood loss greater than 1000 mL in women who had undergone CS (RR 0.43, 95% CI 0.23, 0.78, four trials, 1534 women), but not vaginal birth (RR 0.28, 95% CI 0.06, 1.36, two trials 559 women). The effect of TA on blood loss greater than 500 mL or 400 mL was more pronounced in the group of women having vaginal birth than in women who had CS. Mean blood loss (from delivery until two hours postpartum) was lower in women who received TA versus placebo or no intervention (mean difference MD – 77.79 mL, 95% CI -97.95, -57.64, five trials, 1186 women) and this effect was similar following vaginal birth and CS.Additional medical interventions (moderate quality evidence) and blood transfusions were less frequent in women receiving TA versus placebo or no interventions. Mild side effects such as nausea, vomiting, dizziness were more common with the use of TA (moderate quality evidence). The effect of TA on maternal mortality, severe morbidity and thromboembolic events is uncertain (low quality evidence).
AUTHORS’ CONCLUSIONS:
TA (in addition to uterotonic medications) decreases postpartum blood loss and prevents PPH and blood transfusions following vaginal birth and CS in women at low risk of PPH based on studies of mixed quality. There is insufficient evidence to draw conclusions about serious side effects, but there is an increase in the incidence of minor side effects with the use of TA. Effects of TA on thromboembolic events and mortality as well as its use in high-risk women should be investigated further.
- Does Tranexamic Acid Prevent Postpartum Haemorrhage? A Systematic Review of Randomised Controlled Trials.
Citation
Ker, K., Shakur, H., & Roberts, I. (2016). Tranexamic Acid for Preventing Postpartum Haemorrhage. British Journal of Obstetrics and Gynaecology, 123(11), 1745-52. https://www.ncbi.nlm.nih.gov/pubmed/27558956
Abstract
BACKGROUND:
Postpartum haemorrhage is the leading cause of maternal mortality. Tranexamic acid (TXA) reduces surgical haemorrhage and the risk of death in bleeding trauma patients.
OBJECTIVES:
To assess the effects of TXA on risk of postpartum haemorrhage and other clinically relevant outcomes.
SEARCH STRATEGY:
We searched the MEDLINE, CENTRAL, EMBASE, PubMed, ClinicalTrials.gov and WHO ICTRP electronic databases to May 2015.
SELECTION CRITERIA:
Randomised controlled trials comparing TXA with no TXA or placebo in women giving birth vaginally or by caesarean section.
DATA COLLECTION AND ANALYSIS:
Two authors extracted data and assessed the risk of bias for each trial. Because of data concerns we did not conduct a meta-analysis.
MAIN RESULTS:
We found 26 trials including a total of 4191 women. Examination of the trial reports raised concerns about the quality of the data. Eight trial reports contained identical or similar text and there were important data inconsistencies in several trials. Two trials did not have ethics committee approval. Meta-analysis of baseline variables suggested that randomisation was inadequate in many trials.
CONCLUSIONS:
There is no reliable evidence that TXA prevents postpartum haemorrhage during childbirth. Many of the trials conducted to date are small, low quality and contain serious flaws.
- Prophylactic Tranexamic Acid in Parturients at Low Risk for Post-Partum Haemorrhage: Systematic Review and Meta-Analysis.
Citation
Heesen, M., Böhmer, J., Klöhr, S., Rossaint, R., van de Velde, M., Dudenhausen, J.W., & Straube, S. (2014). Prophylactic Tranexamic Acid in Parturients at Low Risk for Post-Partum Haemorrhage: Systematic Review and Meta-Analysis. Acta Anaesthesiologica Scandinavica 58(9), 1075-85. https://www.ncbi.nlm.nih.gov/pubmed/25069636
Abstract
Tranexamic acid is effective in reducing blood loss during various types of surgery and after trauma. No compelling evidence has yet been presented for post-partum haemorrhage. A systematic literature search of relevant databases was performed to identify trials that assessed blood loss and transfusion incidence after tranexamic acid administration for post-partum haemorrhage. The random effects model was used for meta-analysis. Risk ratios (RRs) and weighted mean differences (WMDs) were calculated with 95% confidence intervals (CIs). Seven trials with a low risk of bias comparing tranexamic acid vs. placebo with a total of 1760 parturients were included in our systematic review and meta-analysis. Blood loss was significantly lower after tranexamic acid use (WMD -140.29 ml, 95% CI -189.64 to -90.93 ml; P<0.00001). Tranexamic acid reduced the risk for blood transfusions (RR 0.34, 95% CI 0.20-0.60, P=0.0001). The incidence of transfusions in the placebo group varied between 1.4% and 33%. When omitting the two trials with the highest incidence of transfusions, the RR was no longer significant. Additional uterotonics were necessary in the placebo groups; gastrointestinal adverse events were more common after tranexamic acid use. Only four cases of thrombosis were found, two each in the tranexamic acid and control groups. Tranexamic acid effectively reduced post-partum blood loss; the effect on the incidence of blood transfusions requires further studies. Only few trials observed adverse events including thromboembolic complications and seizures.
- Tranexamic Acid for Preventing Postpartum Haemorrhage.
Citation
Novikova, N., & Hofmeyr, G.J. (2010). Tranexamic Acid for Preventing Postpartum Haemorrhage. The Cochrane Database of Systematic Reviews 7(7). https://www.ncbi.nlm.nih.gov/pubmed/20614466
Abstract
BACKGROUND:
Postpartum haemorrhage (PPH) is a common and occasionally life-threatening complication of labour. Several options for preventing PPH are available, but further advances in this field are important, especially the identification of safe, easy to use, and cost-effective regimes. Tranexamic acid, which is an antifibrinolytic that is used widely to prevent and treat haemorrhage, merits evaluation to assess whether it meets these criteria.
OBJECTIVES:
To determine, from the best available evidence, whether tranexamic acid is effective for preventing PPH.
SEARCH STRATEGY:
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (12 September 2009).
SELECTION CRITERIA:
All published, unpublished and ongoing randomised controlled trials (RCTs) evaluating the use of tranexamic acid alone or in addition to uterotonics in the third stage of labour or during caesarean section to prevent PPH.
DATA COLLECTION AND ANALYSIS:
Two review authors independently assessed for inclusion all the potential studies identified as a result of the search strategy. We entered the data into Review Manager software and checked for accuracy.
MAIN RESULTS:
We included two RCTs. One RCT of unclear quality of 273 women compared tranexamic acid in two doses (0.5 g intravenously and 1 g intravenously) with aminomethylbenzoic acid (0.5 g intravenously) and with no treatment in women who had vaginal birth. We excluded the aminomethylbenzoic acid arm of this trial (92 patients).Another RCT of 180 women who underwent caesarean section compared tranexamic acid (1 g intravenously given 10 minutes before incision) with placebo.Blood loss greater than 400 ml was less common in women who received tranexamic acid after vaginal birth or caesarean section in the dosage of 1 g or 0.5 g intravenously (two studies, 453 women, risk ratio (RR) 0.51, 95% confidence interval (CI) 0.36 to 0.72). Mean blood loss was lower in the group of women who received intravenous tranexamic acid postpartum (two studies, 361 women, mean difference (MD) -75.17 ml, 95% CI -108.23 ml to -42.12 ml).No serious side effects were reported in women who received tranexamic acid in these trials.
AUTHORS’ CONCLUSIONS:
Tranexamic acid decreases postpartum blood loss after vaginal birth and after caesarean section based on two RCTs of unclear quality which reported on only a few outcomes. Further investigations are needed on efficacy and safety of this regimen for preventing PPH.
- Randomized Controlled Trial of Tranexamic Acid Among Parturients at Increased Risk for Postpartum Hemorrhage Undergoing Cesarean Delivery.
Citation
Sujata, N., Tobin, R., Kaur, R., Aneja, A., Khanna, M., & Hanjoora, V.M. (2016). Randomized Controlled Trial of Tranexamic Acid Among Parturients at Increased Risk for Postpartum Hemorrhage Undergoing Cesarean Delivery. International Journal of Gynecology & Obstetrics 133(3), 312-15. https://www.ncbi.nlm.nih.gov/pubmed/26952346
Abstract
OBJECTIVE:
To assess the effects of tranexamic acid among patients undergoing cesarean delivery who were at high risk of postpartum hemorrhage.
METHODS:
Between August 1, 2012, and April 30, 2013, a randomized controlled trial was performed at a tertiary care center in India. Women undergoing an elective or emergency cesarean delivery who were at high risk for postpartum hemorrhage were enrolled. They were randomly assigned using sealed, opaque envelopes to receive 10mg/kg tranexamic acid or normal saline 10min before skin incision. Anesthesiologists were not masked to group assignment, but patients and obstetricians were. The primary outcome was need for additional uterotonic drugs within 24h after delivery. Analyses were by intention to treat.
RESULTS:
Thirty patients were assigned to each group. Additional uterotonic drugs were required in 7 (23%) patients assigned to tranexamic acid and 25 (83%) patients in the control group (P<0.001).
CONCLUSION:
Intravenous tranexamic acid, administered before skin incision, significantly reduced the requirement for additional uterotonics among women at increased risk for postpartum hemorrhage.
Summary of the Evidence:
| Author (Date) | Level of Evidence | Sample/Setting
(# of subjects/ studies, cohort definition etc.) |
Outcome(s) studied | Key Findings | Limitations and Biases |
| 1. Novikova et al., 2015.
Tranexamic Acid for Preventing Postpartum Haemorrhage |
Systematic review of RCTs
|
-The study included 3,285 healthy women at low risk of excessive bleeding during the postpartum phase
– 9 trials with 2,453 women undergoing elective C-section
-3 trials with 832 women with NSVD |
The review tried to evaluate if tranexamic acid is effective and safe for preventing postpartum hemorrhage compared to placebo or no treatment or to uterotonic agents | -Tranexamic acid decreases the postpartum blood loss and prevent postpartum hemorrhage and need for blood transfusion after both vaginal delivery and C-section, who are at low risk of bleeding
-There is increased incidence of minor side effects, such as, nausea, vomiting and dizziness in patients who received tranexamic acid. There was not enough data available to find out if there can be any serious adverse effects from tranexamic acid administration
|
-The studies that were included had moderate risk of biases for allocation concealment, blinding, randomization, selective reporting and low risk of bias for incomplete data.
-The risk of performance bias was unknown or high in 6 trials
-All the women in all studies received uterotonics but the effect of tranexamic acid in absence of uterotonics was not studied and this might have some effect on the result. |
| 2. Ker et al., 2016
Does Tranexamic Acid Prevent Postpartum Haemorrhage? A Systematic Review of Randomised Controlled Trials |
Systematic review of RCTs | -This review included 26 trials, comparing tranexamic acid with no tranexamic acid or placebo, and had total of 4,191 women
|
-The primary outcome that was evaluated was the effects of tranexamic acid on postpartum hemorrhage
-Secondary outcomes that were assessed were any death, blood loss, blood transfusion, thromboembolic events, any need for surgical intervention, maternal well-being and quality of life and adverse events in babies |
-There was not enough evidence to say that tranexamic acid prevents postpartum hemorrhage during childbirth.
-Fewer women in tranexamic acid group needed blood transfusion. There was no death, surgical intervention or cases of thromboembolic events although 4 women in one trial had DVT
-No study looked at maternal well-being
|
-8 trials had identical text and some of the trials had similar results. So, the researchers asked for the dates of participants’ recruitment and anonymized individual patient’s data, but they received less than half of the information requested. This might have an effect on the result
-Randomization process was inadequate in many of the trials |
| 3. Heesen et al., 2014
Prophylactic Tranexamic Acid in Parturients at Low Risk for Post-Partum Haemorrhage: Systematic Review and Meta-Analysis |
Systemic review and meta-analysis | -7 trials with 1760 parturients with low risk for postpartum hemorrhage
-Inclusion criteria had 12 items: randomization process, allocation concealment, blinding of study participants, care providers and outcome assessors, intention-to-treat analysis, dropout rate, selective outcome reporting, similarity of groups at baseline, co-interventions, and compliance and timing of outcome assessment. Each criterion was scored as yes, no or unclear, and studies were included if studies had six or more criteria scored as yes or unclear.
|
-The study tried to amalgamate the research that involved to see if tranexamic acid is effective in reducing blood loss and postpartum hemorrhage | -Blood loss was significantly lowered after tranexamic acid use.
-The rate of blood transfusion was significantly reduced after TA administration |
-One study did not include the description of their blood transfusion policy and the requirement for blood transfusion may have been different from other studies
-Another limitation is the heterogenicity in the analysis of blood loss |
| 4. Novikova et al., 2010
Tranexamic Acid for Preventing Postpartum Haemorrhage |
Systematic reviews of RCTs | This review included 2 RCTs of unclear quality with 453 women | The study tried to assess the effectiveness of tranexamic acid in preventing postpartum hemorrhage | -This research found that tranexamic acid decreases postpartum blood loss both after vaginal deliveries and C-sections
-No serious side effects of tranexamic acid was reported |
-The study included only 2 trials and both of them had unclear quality
-The randomization process in all of the studies was not explained
-None of the 2 trials were blinded
|
| 5. Sujata et al, 2016
Randomized Controlled Trial of Tranexamic Acid Among Parturients at Increased Risk for Postpartum Hemorrhage Undergoing Cesarean Delivery |
Randomized controlled trial | -60 pregnant women from India, who were undergoing C-sections either electively or emergently and had at least one risk factor for having postpartum hemorrhage.
-Risk factors considered in this study were pregnancy induced hypertension, more than two previous cesarean deliveries, use of oxytocin augmentation for at least 4 hours, chorioamnionitis (oral temperature > 38.5 °C with a high leukocyte count, after ruling out other sources of infection), placenta previa, multiparity (parity >4), general anesthesia, polyhydramnios (amniotic fluid index > 95th percentile for the length of pregnancy as reported on prenatal ultrasonography), fibroids, multiple pregnancies, cholestasis, macrosomia (estimated birth weight > 4 kg) and women with some kind of injury to the genital tract |
The study was trying to evaluate the effects of tranexamic acid among pregnant women who were at high risk of PPH and were undergoing either elective or emergency C-section | The RCT found that IV tranexamic acid, when administered before skin incision, significantly decreased the need for additional uterotonics for women at high risk of postpartum hemorrhage.
-Hemoglobin and hematocrit levels after 48 hours of C-section were significantly lower in the control group than the treatment group. |
-One of the biggest limitations was that the anesthesiologist was not blinded to the group allocation, however, the anesthesiologist had no role in the decision to administer additional uterotonic drugs and, therefore, according to the authors, it should not have affected the result of the study.
-Another limitation was that the risk factors were of different variability. Different patients had different risk factors and this factor could have affected the study result.
-The study was done on women who were undergoing C-section; it did not look at the effect of tranexamic acid on high risk patients who had vaginal delivery
-The study was performed in India, and the healthcare system and the treatment there might be different from the USA, which might have an effect on the result. |
Conclusion(s):
According to the first article, there is enough evidence to say that tranexamic acid (TA) indeed decreases postpartum blood loss and prevents postpartum hemorrhage and also decreases the need for blood transfusions following both C-sections and vaginal deliveries in women who are at a low risk of postpartum hemorrhage. There were over 3,000 participants in this study; however, the studies that were included in the research had mixed qualities. Also, there was not enough evidence to say if TA has any serious adverse effects on mother or the fetus. Similarly, the third article claimed that tranexamic acid effectively reduces postpartum blood loss in people who are at low risk for having post-partum hemorrhage. They also found that the blood transfusion rate was reduced after the administration of tranexamic acid. Article #4 of unclear quality with 453 patients also claimed that tranexamic acid decreases postpartum blood loss, both after NSVD and C-section. However, they also mentioned that further research is needed to assess the efficacy and safety of tranexamic acid. Similar to these articles, the last article also claimed that tranexamic acid was effective in reducing blood loss in patients who had at least one high risk factor of having postpartum hemorrhage and were undergoing either elective or emergent C-section, but this article did not look at the effect of tranexamic acid in patients who had vaginal delivery. Moreover, the risk factors that were considered for this study were of different variability, and this could have affected the result.
The second study mentioned that they could not find reliable evidence to claim that tranexamic acid can prevent postpartum hemorrhage because the studies done so far were small and of low quality with serious flaws. However, they also mentioned that fewer participants in the treatment group needed blood transfusion and there was no death, surgical intervention and no cases of thromboembolic events, although 4 women developed DVT.
Clinical Bottom Line:
When it comes to weight of the evidence, the first article had 3,285 participants and it was a systematic review with 9 RCTs. It is a good article although it has some limitations, such as, moderate risk of biases for allocation concealment, blinding, randomization, not reporting all the results and low risk of bias for incomplete data. The second article had 26 trials with over four thousand participants, but 8 articles had identical texts and similar results. Also, the randomization process was not adequate. The third article had 1,760 patients and included 7 trials, and they clearly defined their inclusion criteria. The last article although had a very small population, it was the only study that looked at the pregnant women who had at least one risk factor of having postpartum hemorrhage, just like the patient mentioned in my clinical scenario. These articles have more weight compared to the fourth one, when it comes to evidence, although all these articles have their own limitations. The first 3 articles have larger population with more trials and less biases. Despite having limitations, we also have to put some weight on the last article, as it was the only article with high risk patients, but it only looked at women who were undergoing C-sections.
One of the important points to talk about is the magnitude of effect that the articles demonstrated. The first four studies had patients who had low risk of having postpartum hemorrhage, and the last study was the only study which had patients who were at high risk of having postpartum hemorrhage, however, it had a very small population. Most of these articles had participants who were at low risk of having postpartum hemorrhage, and, therefore, we do not know much about the effect of tranexamic acid on people who are at high risk of having postpartum hemorrhage. Hence, just based on one small study, we cannot conclude the magnitude of the effect of tranexamic acid on high risk population. However, although the magnitude of effect varied among different studies, the magnitude of effect of tranexamic acid preventing postpartum hemorrhage in low risk patients is huge.
Considering the age and risk factors of my patient, tranexamic acid can be beneficial for her. However, she is considered at a high risk for postpartum hemorrhage, and, as I mentioned before, only one of my study with a small sample of population assessed the impact of tranexamic acid on high risk patients. Also, not all of my articles spoke about the adverse effects. Some of the studies mentioned that tranexamic acid can have some minor side effects, but the 4th article specifically mentioned that there was no serious side effects of tranexamic acid noted, although I cannot put much weight on that article, as it had a small population and randomization process was not adequate. A lot of women worldwide die from postpartum hemorrhage each year; thus, it is important to see what can be done to prevent the postpartum bleeding, and, therefore, this is an important topic to look up, but from these articles, it is not quite clear if the results are clinically significant, as they have small population and many of the studies are of low to moderate quality.
After going through these articles, it seems as if tranexamic acid can prevent postpartum hemorrhage in patients with low risk of hemorrhage. Only last study had patients who were at high risk of postpartum hemorrhage, but that study had only 60 women and had some limitations. So, I cannot say, as to how much of an effect tranexamic acid has on patients who are at high risk of having postpartum hemorrhage, just based on the last study. Although 4 of the articles claim that tranexamic acid can prevent postpartum hemorrhage, none of the studies are big enough to firmly conclude anything. Also, the studies that were included in the systematic reviews, most of them were small trials with significant biases/limitations. While researching, except for my last study, I did not come across any other study done on this topic that had population who were at high risk of postpartum hemorrhage. As for the patient mentioned in the clinical scenario, the evidence does not support or refute the benefit of using tranexamic acid, as most of my studies are based on low risk patients, and the only study with high risk patients had a small number of population and was done outside of the USA. Thus, I would suggest that further studies, preferably a meta-analysis or systematic reviews of large RCTs or an RCT with large sample, need to be performed on this topic, and the studies also need to look at the safety and side effect profile of tranexamic acid. Also, the study must include patients who are at high risk of postpartum hemorrhage and see if tranexamic acid is able to prevent postpartum bleeding in those patients.
