Commentary on "clinical efficacy of tranexamic acid administration via different routes during total hip arthroplasty:study protocol for a prospective randomized controlled trial”

Ido Badash, Brian Wu＊

Keck School of Medicine of University of Southern California (USC), Los Angeles, CA, USA

Perioperative blood loss is a major clinical barrier associated with total hip arthroplasties (THA) (Walker et al., 1997).The use of tranexamic acid (TXA) is considered during THA for its anti fibrinolytic effects, reducing blood loss and the need for blood transfusion following hip replacement.However, there are still concerns in the orthopedic community about the systemic thromboembolic complications of intravenous TXA use, including deep vein thrombosis,pulmonary embolism, myocardial infarctions and cerebrovascular accidents (Gillette et al., 2013). There is some evidence in the literature that topical administration of TXA is also effective at reducing postoperative blood loss, but with a lower incidence of thromboembolic complications(Emara et al., 2014). Thus, the study designed by Zhou et al.(2016), which aims to determine the relative ef ficacy of topical TXA administration versus intravenous administration on reducing postoperative blood loss, will yield clinically signi ficant information for orthopedic surgeons who wish to reduce blood loss following THA but have concerns about the systemic effects of intravenous TXA administration.There are a number of studies investigating the ef ficacy of various forms of TXA administration, but the study protocol created by Zhou et al. (2016) has a number of strengths that may yield additional signi ficant and clinically valuable results on the topic (Wei and Wei, 2014; Danninger and Memtsoudis, 2015; North et al., 2016). First, the study is designed to provide level 1 evidence as a randomized,controlled, double-blinded design that will reduce the presence of selection and reporting biases. Additionally,the authors include a power analysis suggesting that their sample size of 58 subjects per study group should be effective in yielding statistically signi ficant results. Finally, the study’s 1:1:1 paired method for analyzing placebo versus intravenous versus topical administration groups will be effective for reducing variability between the groups and further reducing the risk of confounding. The 1:1:1 paired method is not common in the literature, but with effective pairing assignments could lead to statistically signi ficant results, providing further high-level evidence in investigating the ef ficacy of variable TXA administration.

Although this randomized controlled study protocol is well designed, there are questions about the study protocol that the authors should address. Importantly, the authors state that they will use the 1:1:1 paired method for dividing subjects, but do not present any information on how the pairing of subjects will be performed. Additionally, the authors intend to measure blood loss by making hematocrit measurements prior to surgery and at postoperative day 3.Other studies, however, have found it effective to measure blood loss at various intervals after surgery (24 hours, 48 hours and 5 days after surgery), and used the lowest postoperative levels to measure changes (Gomez-Barrena et al., 2014). It is unclear why the authors intend to measure hematocrit solely at day 3 following surgery, since including other intervals will generate a more convincing estimate of overall blood loss.

The study’s actual method for blood loss measurement represents another area for improvement. In their protocol,Zhou et al. state that they will calculate total blood loss according to erythrocyte changes between preoperative levels and those following surgery. They intend to use the Gross Equation, which utilizes a linear formula to approximate the logarithmic dilution of patient blood through red blood cell loss (Gross, 1983). However, this method does not involve hemoglobin (Hb)-related factors, and thus only indirectly measures anemia in patients. A recent study comparing various formulas for evaluating blood loss in total knee arthroplasties has shown that the Hb balance method, based on Hb measurements rather than hematocrit, is a more reliable method for estimating blood loss (Gao et al., 2015). While the Gross equation is commonly used among surgeons, the authors should consider using the Hb balance method in order to strengthen the validity of their results.

Blood loss associated with THA is a major concern for both patients and surgeons. Therefore, the study from Zhou et al. (2016) investigating the ef ficacy of different forms of TXA administration for reducing blood loss could prove valuable by providing surgeons with additional evidence for controlling this common complication. With additional considerations, we believe that the study by Zhou et al.(2016) may be effective in producing signi ficant results identifying the relative ef ficacy of topical versus intravenous administration of TXA for preventing blood loss.

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