Dataset Information

Alternative routes to intravenous tranexamic acid for postpartum hemorrhage: A systematic search and narrative review.

ABSTRACT:

Objective

To review available data on tranexamic acid (TXA) plasma concentration needed to inhibit fibrinolysis and the time to achieve this concentration when giving TXA by different routes in humans. To identify ongoing trials assessing alternatives to intravenous TXA administration.

Methods

We updated two previous systematic reviews by searching MEDLINE, EMBASE, OviSP, and ISI Web of Science from database inception to July 2021. We also searched the WHO International Clinical Trials Registry Platform for ongoing trials to July 2021. Titles and abstracts were screened for relevant trials. Two reviewers independently reviewed and agreed the trials to be included.

Results

Plasma TXA concentrations over 10 mg/L provide near maximal inhibition of fibrinolysis, with concentrations over 5 mg/L providing partial inhibition. Oral TXA tablets take about 1 h to reach a plasma concentration of 5 mg/L in postpartum women. Studies in healthy volunteers and shocked trauma patients show that intramuscular TXA achieves a plasma level of over 10 mg/L within 15 min. One trial is ongoing to determine the pharmacokinetics of intramuscular and oral solution TXA in pregnant women.

Conclusion

Intramuscular TXA in healthy volunteers and shocked trauma patients reaches therapeutic concentration rapidly. Oral TXA tablets take too long to reach the minimum therapeutic concentration in postpartum women.

SUBMITTER: Shakur-Still H

PROVIDER: S-EPMC9327714 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Alternative routes to intravenous tranexamic acid for postpartum hemorrhage: A systematic search and narrative review.

Shakur-Still Haleema H Grassin-Delyle Stanislas S Muhunthan Kopalasuntharam K Ahmadzia Homa K HK Faraoni David D Arribas Monica M Roberts Ian I

International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 20220601

<h4>Objective</h4>To review available data on tranexamic acid (TXA) plasma concentration needed to inhibit fibrinolysis and the time to achieve this concentration when giving TXA by different routes in humans. To identify ongoing trials assessing alternatives to intravenous TXA administration.<h4>Methods</h4>We updated two previous systematic reviews by searching MEDLINE, EMBASE, OviSP, and ISI Web of Science from database inception to July 2021. We also searched the WHO International Clinical T ...[more]

PMID: 35762806

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Project description:BackgroundNewer research comparing routes of medication administration has extended beyond efficacy as a primary endpoint to incorporate patient preference. However, little is known about the preferences of pregnant women in terms of routes of medication administration, specifically with regards to hemorrhage prevention and control.ObjectiveThis study aimed to understand the preferences of pregnant women in terms of medical interventions to prevent hemorrhage at the time of delivery.Study designSurveys were distributed from April 2022 to September 2022 using electronic tablets at a single urban center with an annual delivery volume of 3000 women per year to women >18 years of age who were either currently pregnant or have been pregnant in the past. Subjects were asked to choose their preferred route of administration from the following options: intravenous, intramuscular, or subcutaneous. The primary outcome was patient preference on the route of medication administration during a hemorrhage event.ResultsThe study cohort included 300 patients, mostly African American (39.8%) followed by White (32.1%), and the majority of the participants ranged from 30 to 34 years of age (31.7%). When asked which method of administration they would prefer to prevent hemorrhage before birth, the results were as follows: 31.1% would prefer intravenous, 23.0% had no preference, 21.2% were unsure, 15.9% preferred subcutaneous, and 8.8% preferred intramuscular administration. In addition, 69.4% of respondents reported that they have never declined or avoided intramuscular administration of medication if recommended by their physician.ConclusionAlthough some survey participants preferred an intravenous route of administration, 68.9% of subjects were unsure, had no preference, or preferred nonintravenous routes. This information is helpful particularly in low-resource settings where intravenous treatments are not readily available or in urgent clinical situations in which intravenous administration routes are not easily obtainable in high-risk patients.

Project description:BackgroundEvery 2 minutes, there is a pregnancy-related death worldwide, with one-third caused by severe postpartum hemorrhage. Although international trials demonstrated the efficacy of 1000 mg tranexamic acid in treating postpartum hemorrhage, to the best of our knowledge, there are no dose-finding studies of tranexamic acid on pregnant women for postpartum hemorrhage prevention.ObjectiveThis study aimed to determine the optimal tranexamic acid dose needed to prevent postpartum hemorrhage.Study designWe enrolled 30 pregnant women undergoing scheduled cesarean delivery in an open-label, dose ranging study. Subjects were divided into 3 cohorts receiving 5, 10, or 15 mg/kg (maximum, 1000 mg) of intravenous tranexamic acid at umbilical cord clamping. The inclusion criteria were ≥34 week's gestation and normal renal function. The primary endpoints were pharmacokinetic and pharmacodynamic profiles. Tranexamic acid plasma concentration of >10 μg/mL and maximum lysis of <17% were defined as therapeutic targets independent to the current study. Rotational thromboelastometry of tissue plasminogen activator-spiked samples was used to evaluate pharmacodynamic profiles at time points up to 24 hours after tranexamic acid administration. Safety was assessed by plasma thrombin generation, D-dimer, and tranexamic acid concentrations in breast milk.ResultsThere were no serious adverse events including venous thromboembolism. Plasma concentrations of tranexamic acid increased in a dose-proportional manner. The lowest dose cohort received an average of 448±87 mg tranexamic acid. Plasma tranexamic acid exceeded 10 μg/mL and maximum lysis was <17% at >1 hour after administration for all tranexamic acid doses tested. Median estimated blood loss for cohorts receiving 5, 10, or 15 mg/kg tranexamic acid was 750, 750, and 700 mL, respectively. Plasma thrombin generation did not increase with higher tranexamic acid concentrations. D-dimer changes from baseline were not different among the cohorts. Breast milk tranexamic acid concentrations were 1% or less than maternal plasma concentrations.ConclusionAlthough large randomized trials are necessary to support the clinical efficacy of tranexamic acid for prophylaxis, we propose an optimal dose of 600 mg in future tranexamic acid efficacy studies to prevent postpartum hemorrhage.

Project description:BackgroundOral tranexamic acid (TXA), if effective in reducing blood loss after delivery for women experiencing primary PPH, could be administered where parenteral administration is not feasible. This trial assessed the efficacy, safety, and acceptability of oral TXA when used as an adjunct to sublingual misoprostol to treat postpartum hemorrhage (PPH) following vaginal delivery.MethodsFrom October 2016 to January 2018, women presenting at four hospitals in Senegal and Vietnam for vaginal delivery were screened for enrollment in the trial. Women diagnosed with postpartum hemorrhage (defined as blood loss ≥700 ml) were randomized to receive either oral TXA (1950 mg) or placebo in addition to 800 mcg sublingual misoprostol. Postpartum blood loss was measured using a calibrated drape. Blood loss for all PPH cases was recorded for 2 h after administration of the drugs. The primary outcome measure was the proportion of women with bleeding controlled with the trial regimen without recourse to further treatment. Secondary outcomes including the rate of severe PPH, mean/median blood loss, use of additional uterotonics and/or interventions side effects, and acceptability were also recorded.ResultsOf the 258 women who received treatment for PPH, 128 received placebo and misoprostol and 130 received TXA and misoprostol. The proportion of women who had active bleeding controlled with trial drugs alone and no additional interventions was similar in both groups: 77(60.2%) placebo; 74 (56.9%) TXA, p = 0.59). Use of other interventions to control bleeding, including uterotonics, did not differ significantly between groups. Median blood loss at PPH diagnosis was 700 ml in both groups. Uterine atony alone or in addition to another cause contributed to over 90% of PPH cases reported (92.2% placebo vs. 91.5% TXA), other causes included perineal and cervical lacerations and retained placenta. Reports of side effects and acceptability were similar in the two groups.ConclusionAdjunct use of oral TXA with misoprostol to treat PPH resulted in similar clinical and acceptability outcomes when compared to treatment with misoprostol alone.Trial registrationThis trial was registered with ClinicalTrials.gov, number NCT02805426. Registered on 3 September 2016.

Project description:BackgroundTranexamic acid (TXA) is well-established as a versatile oral, intramuscular, and intravenous (IV) antifibrinolytic agent. However, the efficacy of IV TXA in reducing perioperative blood transfusion in spinal surgery is poorly documented.MethodologyWe conducted a meta-analysis of randomized controlled trials (RCTs) and quasi-randomized (qi-RCTs) trials that included patients for various spinal surgeries, such as adolescent scoliosis surgery administered with perioperative IV TXA according to Cochrane Collaboration guidelines using electronic PubMed, Cochrane Central Register of Controlled Trials, and Embase databases. Additional journal articles and conference proceedings were manually located by two independent researchers.ResultsTotally, nine studies were included, with a total sample size of 581 patients. Mean blood loss was decreased in patients treated with perioperative IV TXA by 128.28 ml intraoperatively (ranging from 33.84 to 222.73 ml), 98.49 ml postoperatively (ranging from 83.22 to 113.77 ml), and 389.21 ml combined (ranging from 177.83 to 600.60 ml). The mean volume of transfused packed cells were reduced by 134.55 ml (ranging 51.64 to 217.46) (95% CI; P = 0.0001). Overall, the number of patients treated with TXA who required blood transfusions was lower by 35% than that of patients treated with the comparator and who required blood transfusions (RR 0.65; 95% CI; 0.53 to 0.85; P<0.0001, I(2) = 0%). A dose-independent beneficial effect of TXA was observed, and confirmed in subgroup and sensitivity analyses. A total of seven studies reported DVT data. The study containing only a single DVT case was not combined.ConclusionsThe blood loss was reduced in spinal surgery patients with perioperative IV TXA treatment. Also the percentage of spinal surgery patients who required blood transfusion was significantly decreased. Further evaluation is required to confirm our findings before TXA can be safely used in patients undergoing spine surgery.

Dataset Information

Alternative routes to intravenous tranexamic acid for postpartum hemorrhage: A systematic search and narrative review.

Objective

Methods

Results

Conclusion

Publications

Alternative routes to intravenous tranexamic acid for postpartum hemorrhage: A systematic search and narrative review.

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