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. Author manuscript; available in PMC: 2021 Apr 12.
Published in final edited form as: J Thromb Haemost. 2018 Jun 21;16(7):1369–1382. doi: 10.1111/jth.14148

Fig. 2.

Fig. 2.

Antifibrinolytic therapy increased clot stability ex vivo, but did not improve the bleeding phenotype or the response to rFVIIa in vivo in rats with congenital hemophilia A. (A) Native clot formation in recalcified whole blood as measured by changes in amplitude over time. Clot formation was significantly reduced in whole blood from tranexamic acid (TXA)-treated and vehicle-treated rats. ¤P ≤ 0.05 for vehicle versus recombinant activated factor VII (rFVIIa); #P ≤ 0.05 for vehicle versus rFVIIa + TXA; *P ≤ 0.05 for TXA versus rFVIIa and TXA versus rFVIIa + TXA. (B) Whole blood clot formation and stability as measured by changes in amplitude over time in the tissue factor (TF)/tissue-type plasminogen activator (t-PA) assay. TXA had a significant clot-stabilizing effect ex vivo, as rats treated with TXA or a with combination of rFVIIa and TXA were almost completely resistant to a fibrinolytic challenge. $P ≤ 0.05 for rFVIIa + TXA versus vehicle and rFVIIa + TXA versus rFVIIa; §P ≤ 0.05 for TXA versus vehicle; *P ≤ 0.05 for TXA versus rFVIIa. In both (A) and (B), n = 5, with two technical replicates for each rat (mean ± standard error of the mean [SEM]). Recalcification and TF/t-PA data were analyzed with Welch’s ANOVA with the Games–Howell post hoc test. (C) Individual bleeding profiles of treated rats: a graphical representation of bleeding profiles, in which horizontal lines represent the entire bleeding profile of a single rat, and each bar in a line represents a single bleeding episode for that rat. (D) The total blood loss of FVIII−/− rats subjected to the tail vein transection (TVT) bleeding model shown as individual observations; horizontal and error bars indicate mean ± SEM. In the TVT bleeding model, no significant differences for TXA alone versus vehicle or rFVIIa alone versus rFVIIa and TXA were detected. However, blood loss was significantly reduced in rFVIIa-treated and rFVIIa + TXA-treated rats. Blood loss was analyzed with an ordinary ANOVA with Bonferroni’s correction for multiple comparisons, except for wild-type (WT) rats. *P < 0.05; ***P < 0.001. FVIII−/− rats were used, unless noted otherwise. Hgb, hemoglobin.