Use of Tranexamic Acid (TXA) on reducing blood loss during scoliosis surgery in Chinese adolescents

Pharmacological therapies are commonly used to reduce blood loss and blood transfusions
in surgery. Tranexamic acid or TXA was previously shown to be as effective as other
antifibrinolytics but at a much lower cost 21], 22]. The safety and efficacy of TXA are still controversial probably due to the difference
in the dose of TXA used and type of surgery 21], 23]. In this retrospective study, it was shown that TXA could significantly reduce blood
loss with up to 53.0 % reduction which is in concordance with some similar studies
19], 24], 25]. Intraoperative estimated blood loss was shown to be decreased by 56.8 % for patients
using TXA, reported from a comparative analysis of 106 consecutive adolescents undergoing
PSF in Japan 14]. Moreover, contributing factors that could alter blood loss were included in regression
analysis, thus proving the efficacy of TXA in reducing blood loss even after adjustment
with possible confounding factors, clotting capabilities and infusion of coagulation
factors. All the patients in this study showed no severe complications which demonstrated
the safety of TXA.

The use of TXA in major paediatric surgery was proven to be better than the other
commonly used antifibrinolytic agents e.g., aprotinin and aminocaproic acid 20], 21], 23], 26]. Results from a recent randomized double-blinded pilot study studying the efficacy
of aminocaproic acid versus TXA in paediatric spinal deformity surgery concluded that
TXA was associated with a lower allogenic transfusion requirement, less alteration
in postoperative clotting studies, and a trend toward lower blood loss in paediatric
posterior spinal fusion patients 24]. The cost of TXA is higher than aminocaproic acid, therefore, the use of TXA is excellent
for long and complex surgeries e.g., scoliosis and surgeries with the use of autograft
and long fusion levels 27]. Aprotinin was associated with severe side effects e.g., myocardial infraction, heart
failure, and renal failure 28]–31], although it was effective in reducing total blood loss after paediatric cardiac
surgery 32]. Higher costs when using aprotinin make TXA a better option with similar efficacy.
In this study, we clearly proved that the use of TXA in surgical scoliotic cases greatly
reduced the volume of whole blood and blood from cell saver transfused back to the
patients, although no comparison on the use of other antifibrinolytic agents were
carried out because of the standard and consistency of clinical practice.

Studies tried to look for the factors other than the use of TXA affecting the total
blood loss, however, no conclusion has been clearly made probably as a result of limited
data collected for data analysis. Discussions on autologous blood transfusion and
reinfusion of salvaged blood from cell saver machine being the causative factor have
been introduced for over a decade 6], 20], 25]. Transfusion requirements and coagulation parameters were first introduced by Sethna
et al. in a study with 44 children and adolescents undergoing scoliotic surgical corrections
through comparative analyses 5]. Other factors like age, gender, and number of vertebral levels fused, were introduced
in recent publications 20], 25]. Length of hospital stay was discussed in a couple of reports, while this was the
secondary clinical outcome of the use of TXA instead of being a factor on controlling
total blood loss 33], 34]. At the ever-vigorous surgical environment, there are many factors which can affect
the total blood loss, not solely dictated by the use of TXA, and these have to be
controlled for us to draw a conclusion on the effect of TXA on controlling blood loss
at surgery. This study collected information in possible confounding factors on total
blood loss with the use of TXA at surgery in Chinese AIS patients, and confirmed the
efficacy of TXA after controlling major confounding factors.

In this study, total blood loss estimated by anaesthesia technician was significantly
reduced in patients using TXA at surgery. At the same time, volume of blood transfused
from cell saver was also much reduced in TXA group. A recent study on the use of TXA
in 49 surgical AIS patients undergoing posterior spinal fusion by a single surgeon
showed similar findings on great decrease in total blood loss as of the present study
20]. The volume of blood transfused, however, did not appear to be affected 20]. In this study, the volume of salvaged blood from cell saver was much decreased in
TXA group. Nonetheless, the total amount of blood loss and cell saver blood returned
to the patients were relatively huge. These were because the spinal curvatures were
large and the fusion levels were high. Similar results were obtained from surgeries
on severe curvatures 19], 33]. In summary. we have established a very tight transfusion protocol for AIS surgery,
which makes the results different from the study from Lykissas and colleagues 20]. A recent randomized control trial was carried out to look for the efficacy of different
antifibrinolytics in AIS. TXA and epsilon-aminocaproic acid effectively reduced estimated
and actual blood loss, as well as declined in haematocrit after surgery compared with
saline solution 25].

The present study also gives us an idea on the rate of blood loss decrease after using
TXA at surgery with proper adjustment of confounding factors. Regarding to the transfusion
rate being another important parameter evaluating the efficacy of antifibrinolytics,
authors, the factors affecting the transfusion rate is mainly a surgeon-decisive issue,
namely patient comorbidities, patient preference, preoperative blood donation, and
clinical judgment 25]. Similar findings were found in another RCT published in Cochrane Library 35]. A systematic review and meta-analysis on the use of intravenous TXA in spinal surgery
carried out in China showed much reduced volume of blood loss and volume of transfused
packed cells, although patient age was one of the study exclusion criteria making
the analyses not totally applicable to present study 26]. An extended multi-centre review on the use of different antifibrinolytic agents
to reduce blood loss during vertebral column resection in paediatrics also confirmed
the effectiveness of reduced estimated blood loss when using TXA during surgery after
normalized to patient size and levels excised 19]. Similar observations are well-documented in many previous studies 5], 6], 15], 16], 18], 19], 33]–39]. The present study is the first study on the evaluation of efficacy of TXA in Chinese
AIS patients, with the novel findings of factors affecting total blood loss.

This is the first report on the use of TXA in surgical Chinese AIS patients. The factors
affecting the total blood loss are derived by a series of sensitivity analysis through
different regression models with the proper controlling of confounding factors.

Limitations

There are limitations we have to consider in this study. The small sample size and
retrospective nature of this comparative study would limit the data generalizability.
Our surgeons and anaesthetists had many years of experience in spinal surgery before
beginning of this study, the ever-improving surgical skills over the years could influence
the amount of total blood loss. The concern on the effect of the improvement of surgical
skills on the amount of total blood loss was proven minimal after a closed monitoring
of difference of total surgical blood loss over the study period. Yet a prospective
dose-ranging study is still required to determine the optimal dose for spine surgery
on patients with idiopathic scoliosis. To provide additional information on the efficacy
and safety of TXA, multi-centre randomized prospective analysis in the future is warranted.