Abstract
Dear editor,
We would like to thank the authors of the letter for their interest in our study and their comments.
Our study prospectively compared the daily blood loss transition between the groups with and without topical administration of TXA after cruciate retaining (CR) and posterior stabilized (PS) total knee arthroplasty (TKA). The topical administration of TXA for reduction in blood loss was effective up to 48 h after both CR and PS designs of TKA. The blood loss after action of TXA tended to be greater in the TXA groups; this unexpected phenomenon was designated as “the paradoxical blood loss.”
We think that the authors of the letter have concerns about the methodological limitation and clinical relevance against our study. They commented following limitations of our study. First, exquisite laboratory analysis including fibrinolytic parameters was not conducted to support the proposed hypothesis (the delayed fibrinolytic action) for mechanism of the paradoxical blood loss. Second, the clinical relevance of the paradoxical bleeding phenomenon could not be demonstrated. It was not identified to affect the transfusion rate, complications, and patient’s recovery. Third, the study design was not elaborate in terms of the practice of the drain clamping and blinding to the group allocation for the analysts. Last, it could not be assured whether the paradoxical blood loss would also occur in TKAs without tourniquet. We agree with the critiques, and some of these were already described as our limitations in the manuscript.
However, we cannot agree on some critiques of the study design. The use of TXA was randomly assigned by a number previously created by online number generator. Regarding the comment for the bleeding diatheses, there were no significant differences in the preoperative hemoglobin, platelet, activated partial thromboplastin time, and international normalized ratio. The frequency of the anticoagulant use was also similar preoperatively between the groups with and without TXA.
Despite some limitations, our article is thought to be valuable in reporting an unexpected phenomenon of TXA that was not previously reported. Our new finding will be able to help develop a more effective administration protocol of TXA. Especially, it can provide an evidence for a protocol to add intravenous or oral TXA administration after topical intraoperative injection of TXA. In addition, as commented in the letter, our study can fuel more high-quality studies to unravel the pharmacokinetic complexities of TXA and its clinical significance. We hope that such further studies will be able to provide a fundamental reason why risk of thromboembolism is not increased even with the use of TXA. Many studies have empirically reported that the use of TXA does not increase thromboembolic risk, but the pharmacokinetic basic evidence has never been suggested. 1,2 If the delayed fibrinolytic action, suggested as the mechanism of paradoxical blood loss theoretically in our study, is clearly demonstrated, it will contribute an establishment of the pharmacokinetic evidence for not increasing thromboembolic risk with TXA use. The establishment will be able to serve as a defense for surgeons in legal problems due to thromboembolic events after TXA use.
We appreciate again the interest and thoughtful comments in the letter. We look forward to further research with elaborate design and large sample size on the novel finding of our study.
