Tranexamic acid dose–response relationship for antifibrinolysis in postpartum haemorrhage during Caesarean delivery: TRACES, a double-blind, placebo-controlled, multicentre, dose-ranging biomarker study

Ducloy-Bouthors, A.-S.; Gilliot, Sixtine; Kyheng, Maéva; Faraoni, David; Turbelin, Alexandre; Keïta-Meyer, Hawa; Rigouzzo, A.; Moyanotidou, Gabriela; Constant, Benjamín; Broisin, F.; Gouez, Agnès Le; Favier, Rémi; Peynaud, Edith; Ghesquière, Louise; Lebuffe, Gilles; Duhamel, Alain; Allorge, Delphine; Susen, Sophie; Hennart, Benjamin; Jeanpierre, Emmanuelle; Odou, Pascal; Huissoud, Cyril; Garabédian, Charles; Lassalle, Fanny; Mercier, Frédéric; Barré-Drouard, C.; Estevez, Max Gonzalez; Corouge, J.; Baptiste, Anne-Sophie; Dalmas, A.-F.; Richart, P.

doi:10.1016/j.bja.2022.08.033

Cited by 15 publications

(14 citation statements)

References 30 publications

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“…To find the optimal dose to inhibit fibrinolysis, the recent multicenter TRACES trial randomized 175 women with a bleeding volume of more than 800 ml after cesarean section to receive a dosage of 1 g TXA, 0.5 g TXA or placebo. Although a dose of 1 g but not 0.5 g significantly reduced levels of fibrinolysis markers, these findings were not correlated with improved clinical outcomes, as patients in all three treatment arms did not differ in duration or amount of bleeding or the incidence of life-threatening blood loss above 2500 ml [31 ▪▪ ].…”

Section: Tranexamic Acidmentioning

confidence: 89%

“…Other trials identified a positive kinetic of fibrinolytic biomarkers such as plasmin-antiplasmin complexes or D-dimers, accumulating as a breakdown product of cross-linked fibrin in patients with significant obstetric bleeding without antifibrinolytic treatment. These findings suggest an insufficient sensitivity of viscoelastic assays to detect hyperfibrinolysis in this setting [30,31 ▪▪ ].…”

Section: Tranexamic Acidmentioning

confidence: 90%

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Coagulation management and transfusion in massive postpartum hemorrhage

Massoth

Wenk

Meybohm

et al. 2023

Current Opinion in Anaesthesiology

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Purpose of ReviewExcessive bleeding during and following childbirth remains one of the leading causes of maternal mortality.Recent findingsCurrent guidelines differ in definitions and recommendations on managing transfusion and hemostasis in massive postpartum hemorrhage (PPH). Insights gained from trauma-induced coagulopathy are not directly transferable to the obstetric population due to gestational alterations and a differing pathophysiology.SummaryFactor deficiency is uncommon at the beginning of most etiologies of PPH but will eventually develop from consumption and depletion in the absence of bleeding control. The sensitivity of point-of-care tests for fibrinolysis is too low and may delay treatment, therefore tranexamic acid should be started early at diagnosis even without signs for hyperfibrinolysis. Transfusion management may be initiated empirically, but is best to be guided by laboratory and viscoelastic assay results as soon as possible. Hypofibrinogenemia is well detected by point-of-care tests, thus substitution may be tailored to individual needs, while reliable thresholds for fresh frozen plasma (FFP) and specific components are yet to be defined. In case of factor deficiency, prothrombin complex concentrate or lyophilized plasma allow for a more rapid restoration of coagulation than FFP. If bleeding and hemostasis are under control, a timely anticoagulation may be necessary.

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Section: Tranexamic Acidmentioning

confidence: 89%

Section: Tranexamic Acidmentioning

confidence: 90%

Coagulation management and transfusion in massive postpartum hemorrhage

Massoth

Wenk

Meybohm

et al. 2023

Current Opinion in Anaesthesiology

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“…Eine Dosisfindungsstudie konnte keinen klinischen Unterschied hinsichtlich Blutverlust, Transfusionsrate oder Therapieimplikation bei Gabe von 1 g TXA, 0,5 g TXA oder Placebo bei 175 Frauen mit > 800 ml Blutverlust nach Sectio feststellen. Die Dosierung von 1 g TXA zeigte sich jedoch überlegen, um die Plasmaspiegel von Fibrinolysemarkern wie D-Dimere als Gerinnselabbauprodukt zu reduzieren [30].…”

Section: Merkeunclassified

Postpartale Hämorrhagie

Massoth,

Helmer,

Pecks

et al. 2023

Anästhesiol Intensivmed Notfallmed Schmerzther

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Die postpartale Hämorrhagie tritt bei etwa 4 % aller Entbindungen in industrialisierten Ländern auf und zeigt eine steigende Inzidenz. Die schwerwiegenden Auswirkungen auf das maternale Outcome erfordern eine rasche Diagnosestellung und Ursachenidentifizierung mit nachfolgendem zielgerichtetem sowie interdisziplinärem Management der Blutstillung, Kreislaufstabilisierung und Gerinnungstherapie. Epidemiologie Die Reduktion der Müttersterblichkeit wurde von den Vereinten Nationen und der World Health Organization (WHO) als eines der globalen Ziele für nachhaltige Entwicklung deklariert. Dennoch verstarben im Jahr 2020 weltweit etwa 270 000 Frauen an den Folgen von Schwangerschaft und Geburt, davon 95 % in Drittwelt-und Schwellenländern. Nachdem die Rate mütterlicher Sterbefälle in den letzten 20 Jahren um etwa 34 % gesunken ist, veröffentlichte die WHO nun eine Stagnation dieser Entwicklungund sie berichtete einen signifikanten Wiederanstieg der Mortalitätsraten in Europa und Nordamerika seit 2016 [1].Mit etwa 27 % aller Todesfälle weltweit und bis zu 16 % in westlichen Ländern gehört die postpartale Hämorrhagie (PPH) dabei zu den Hauptursachen maternaler Mortalität [2]. Die PPH betrifft bis zu 4% aller Entbindungen, die schwere PPH etwa 0,3% mit jeweils steigender Inzidenz. Diese Entwicklung ist dabei auch auf die wachsende Anzahl mütterlicher Risikofaktoren und die steigende Sectiorate mit konsekutiven Folgekomplikationen wie Plazentationsstörungen und Uterusnarben zurückzuführen [3,4,5].

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“…More limited data are available assessing TXA pharmacodynamics in patients with PPH. Hemostatic variables, including fibrinolytic markers, have been reported in a secondary data analysis from a randomized trial of two TXA regimens (1 g TXA, 0.5 g TXA) versus placebo in patients who experienced PPH during cesarean delivery [21]. Patients who received 1 g TXA experienced a significant decrease in both D-dimer levels at 120 min and plasmin-antiplasmin levels at 30 min when compared to their baseline values.…”

Section: Pharmacologymentioning

confidence: 99%

Evaluating tranexamic acid for the prevention and treatment of obstetric hemorrhage

Kowalczyk,

Cecconi,

Butwick

2023

Current Opinion in Obstetrics &Amp; Gynecology

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Purpose of review Tranexamic acid (TXA) has emerged as a promising pharmacological adjunct to treat and prevent postpartum hemorrhage (PPH). We provide an overview of TXA, including its pharmacology, key findings of randomized trials and observational studies, and critical patient safety information. Recent findings Pharmacokinetic data indicate that TXA infusions result in peak plasma concentration within 3 min (range: 1–6.6 min). Ex-vivo pharmacodynamic data suggest that low-dose TXA (5 mg/kg) inhibits maximum lysis for at least 1 h. In predominantly developing countries, TXA has demonstrated a 19% reduction in the risk of bleeding-related death among patients with PPH. Based on high-quality randomized trials, TXA prophylaxis does not effectively reduce the risk of PPH during vaginal delivery and is likely ineffective in reducing the PPH risk during cesarean delivery. TXA exposure does not increase the risk of maternal thrombotic events. Maternal deaths have occurred from accidental intrathecal TXA injection from look-alike medication errors. Summary TXA has shown promise as an important adjunct for PPH treatment, especially in low-resource settings. However, TXA is not recommended as PPH prophylaxis during vaginal or cesarean delivery. Patient safety initiatives should be prioritized to prevent maternal death from accidental intrathecal TXA injection.

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Tranexamic acid dose–response relationship for antifibrinolysis in postpartum haemorrhage during Caesarean delivery: TRACES, a double-blind, placebo-controlled, multicentre, dose-ranging biomarker study

Cited by 15 publications

References 30 publications

Coagulation management and transfusion in massive postpartum hemorrhage

Coagulation management and transfusion in massive postpartum hemorrhage

Postpartale Hämorrhagie

Evaluating tranexamic acid for the prevention and treatment of obstetric hemorrhage

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