Consumptive coagulopathy associated with aortic disease progresses to the state of enhanced fibrinolytic-type DIC (EFDIC). Yamada et al. reported that EFDIC is characterized by decreased platelet count, fibrinogen and α2PI and increased TAT, PIC, FDP and D-dimer, while PT and APTT are less prolonged [15]. Elevated PIC is also characteristic, particularly in EFDIC, with some previous reports describing PIC > 10 g/mL as characteristic of EFDIC. The data from this study showed a trend generally consistent with these characteristics of EFDIC, but median PIC was 5.0 g/mL (range, 2.1–10.9 μg/mL), which is low for EFDIC. Previous case reports of CDAAD showed PICs ranging from 0.8 to 10.6 μg/mL, generally similar to the present study [6,7,8,9,10,11, 16, 17]. The degree of PIC elevation in CDAAD may thus be characterized as “not elevated”.

The dose of TXA administered in this study was quite low, around 30% of the dose normally used, and resulted in a significant reduction in FDP, one measure of increased fibrinolysis, but little reduction in PIC. A possible reason explaining why such low doses were effective in improving bleeding symptoms is that fibrinolysis is not as severe in CDAAD and is not the only major cause of bleeding symptoms.

The abnormal coagulation seen in the present study was not only fibrinolytic, but also coagulopathic, considering that TAT was also elevated. Therefore, a complex coagulation abnormality was considered to be caused by an imbalance between coagulation and fibrinolysis, rather than a state of increased fibrinolysis alone, suggesting that the inhibition of fibrinolysis by TXA does not contribute to the improvement of bleeding symptoms alone. Another possibility is that TXA-induced fibrinolysis inhibition may lead to an improvement in overall coagulation balance, in turn leading to improved bleeding symptoms.

Although oral TXA produced improvements in bleeding tendency, no significant difference in JMHW DIC score was identified. This is because platelet count, fibrinogen, and FDP must improve significantly to be reflected in an improved score. Another reason may be that this scoring system reflects improvements not only in bleeding symptoms, but also in items not directly related to coagulability, such as underlying disease and organ damage. In any case, the effect of low-dose TXA appeared to be an improvement in bleeding tendency, while DIC may not be improved.

However, although not evaluated in the present study, Aoki et al. reported that concomitant use of long-term TXA (1500 mg/day for 6 months) in endovascular repair procedures resulted in a size reduction of aneurysms without any severe adverse events [18]. As such, TXA may not only directly improve blood coagulability, but also have an effect on the underlying aortic lesion, which would make this a very attractive treatment for CDAAD.

With regard to safety, deaths due to thrombotic complications have been reported with the use of TXA as a single agent in DIC with underlying diseases other than aortic disease [15, 19, 20]. However, no reports to date have described thrombosis with TXA monotherapy for CDAAD, and no thrombotic events occurred in the present study. No other side effects could be clearly attributed to TXA.

Retrospectively, all cases in the present study continued TXA for bleeding prophylaxis and CDAAD control after achieving hemostasis. This is because relapse of severe bleeding symptoms after TXA discontinuation have been reported, and prolonged concomitant use of anticoagulants and TXA has been reported as useful for controlling bleeding symptoms and DIC [10, 21]. However, heparin is mainly used as the anticoagulant, and injections cannot be avoided. Several reports have described direct oral anticoagulants as an effective additional oral pharmacotherapy for CDAAD [22, 23]. However, direct oral anticoagulants cannot be used in patients with reduced renal function and are therefore often unsuitable in patients with CDAAD, many of whom have CKD. TXA also requires dose adjustment in CKD patients, with Ma et al. recommending oral doses of 7.5–15 mg/kg/day for non-dialysis CKD patients [24]. The dose of approximately 5 mg/kg/day adopted in the present study can be administered to non-dialysis CKD patients without problems.

Finally, several limitations need to be considered in this study. First, this was a retrospective study of a small number of patients and TXA cannot be concluded to be effective based on improved outcomes. Two patients underwent EVAR during the observation period, and hemostatic effects of factors other than TXA cannot be ruled out. Future studies should assess the clinical efficacy of TXA in well-conditioned, prospective trials, while detailed assessment of blood coagulation performance is needed to determine exactly which coagulation findings are altered and which bleeding trends are improved by TXA.