Effect of Tranexamic Acid on Coagulation and Fibrin Clot Properties in Children Undergoing Craniofacial Surgery

Abstract

Objective Craniosynostosis surgery in small children is very often associated with a high blood loss. Tranexamic acid (TXA) reduces blood loss during this procedure, although the potential underlying coagulopathy in these children is not known in detail. Objective was to determine the nature of any coagulopathy found during and after craniosynostosis surgery and to characterize the effect of TXA on fibrin clot formation, clot strength, and fibrinolysis. Materials and Methods Thirty children received either TXA (bolus dose of 10 mg/kg followed by 8 hours continuous infusion of 3 mg/kg/h) or placebo. Dynamic whole blood clot formation assessed by thromboelastometry, platelet count, dynamic thrombin generation/thrombin-antithrombin, clot lysis assay, and fibrinogen/factor XIII (FXIII) levels were measured. Additionally, clot structure was investigated by real-time live confocal microscopy and topical data analysis. Results Increased ability of thrombin generation was observed together with a tendency toward shortened activated partial thromboplastin time and clotting time. Postoperative maximum clot firmness was higher among children receiving TXA. FXIII decreased significantly during surgery in both groups.Resistance toward tissue plasminogen activator-induced fibrinolysis was higher in children that received TXA, as evidenced by topical data analysis and by a significant longer lysis time. Fibrinogen levels were higher in the TXA group at 24 hours. Conclusion A significant coagulopathy mainly characterized by changes in clot stability and not parameters of thrombin generation was reported. Tranexamic acid improved clot strength and reduced fibrinolysis, thereby avoiding reduction in fibrinogen levels.

Haemostatic effect of adding tranexamic acid to emicizumab prophylaxis in severe haemophilia A: A preclinical study

“…Endogenous thrombin potential in mice that received emicizumab only was 363±130 nm.min (mean±SD) and 363±95 nm.min in those treated with emicizumab+TxAc ( P > .05, Mann Whitney U test). In accordance with previous clinical studies, the suppression of fibrinolytic activity by TxAc has no additional procoagulant effect on thrombin generation capacity 13,14 . We previously showed that thromboelastography was very sensitive to the TxAc effect; curves and thromboelastography parameters could be fully normalized with TxAc alone without any contribution from exogenous factor VIII 2 .…”

“…In accordance with previous clinical studies, the suppression of fibrinolytic activity by TxAc has no additional procoagulant effect on thrombin generation capacity. 13,14 We previously showed that thromboelastography was very sensitive to the TxAc effect; curves and thromboelastography parameters could be fully normalized with TxAc alone without any contribution from exogenous factor VIII. 2 However, this observation is inconsistent with clinical experience where TxAc alone is not usually sufficient to control bleeding in patients with severe haemophilia A.…”

Tranexamic acid in plastic surgery: routes of administration and dosage considerations

“…Of the reviewed studies, fifteen assessed the use of TXA in craniofacial surgery procedures [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43]. Of these, nine were retrospective cohort studies [29-31, 34, 35, 38-40, 42], and six were randomized controlled clinical trials [32,33,36,37,41,43]. Study sample ranged from 25 to 187 patients, apart from a single retrospective cohort study of 1638 patients.…”

“…Eight studies reported a notable decline in transfusion requirements, owing to decreased intraoperative bleeding, ranging from 19 to 85% [28,[31][32][33][34][37][38][39]. Other notable outcomes included a clearer surgical field [36], shorter length of hospital stay [40], lower drop in postoperative hemoglobin level, higher postoperative estimated red cell volume [30], and decreased surgical drain Fig.…”

Effect of tranexamic acid on markers of inflammation in children undergoing craniofacial surgery

“…TXA is a synthetic lysine analog that binds reversibly to lysine receptor sites on plasminogen. This step reduces conversion of plasminogen to plasmin whereby the level of plasmin drops significantly and prevents fibrin degradation and supports preservation of the fibrin network 3,4 . Both plasminogen and plasmin play pivotal role as inflammatory mediators.…”