In March 2019, OrthoBuzz covered a JBJS study by Rudasill et al. that found a progressively increasing risk of bleeding requiring transfusion among total knee arthroplasty (TKA) patients who had a preoperative International Normalized Ratio (INR) >1. (INR is a standardized measure of how long it takes blood to clot—the higher the number, the longer the clotting time.) These authors also found a significantly increased risk of infection in TKA patients with INR >1.5. and an increased risk of mortality within 30 days of surgery among those with an INR >1.25 to 1.5.
In the January 2, 2020 issue of JBJS, the same team of researchers report findings from a similarly designed NSQIP-based study of patients undergoing total hip arthroplasty (THA). The authors evaluated data from >17,500 patients who underwent a primary THA between 2005 and 2016 and who also had an INR value documented within 2 days prior to joint replacement. Rudasill et al. stratified these patients into 4 groups based on preoperative INRs: ≤1, >1 to <1.25, 1.25 to <1.5, and ≥1.5).
After adjustment, the authors found a significant, independent effect between increased preoperative INR and increased bleeding requiring transfusion and mortality. Specifically, bleeding risk became evident at INR ≥1.25, and patients with INR ≥1.5 were at a significantly increased risk of mortality. The length of hospital stay also increased significantly as INR class increased.
The authors suggest that “current INR targeting [INR <1.5 for elective orthopaedic surgery] may not be strict enough to minimize adverse outcomes for patients undergoing primary total hip arthroplasty.” While admitting that these findings are not likely to change the day-to-day practice of orthopaedic surgeons, the authors say they “may influence preoperative risk stratification for those patients with elevated INR.”
The recent orthopaedic literature, including a 2017 JBJS study, provides substantial evidence that oral and intravenous tranexamic acid (TXA) are equivalent in their effectiveness at reducing blood loss after total hip arthroplasty (THA)—with oral administration being less expensive and more convenient. But what are the optimal doses and timing of oral TXA in the setting of THA?
The findings of a randomized controlled trial by Wang et al. in the March 6, 2019 issue of JBJS go a long way toward answering that question. The authors randomized 200 patients undergoing primary THA to 1 of 4 groups, with all patients receiving an intraoperative topical dose of 1.0 g of TXA and a single dose of 2.0 g of TXA orally at 2 hours postoperatively. In addition,:
- Group A received 1.0 g of oral placebo at 3, 9, and 15 hours postoperatively
- Group B received 1.0 g of oral TXA at 3 hours postoperatively and 1.0 g of placebo at 9 and 15 hours postoperatively
- Group C received 1.0 g of oral TXA at 3 and 9 hours postoperatively and 1.0 g of placebo at 15 hours postoperatively
- Group D received 1.0 g of TXA at 3, 9, and 15 hours postoperatively
The mean total blood loss during hospitalization was significantly less in Groups B, C, and D (792, 631, and 553 mL, respectively) than in Group A (984 mL). Groups C and D had lower mean reductions in hemoglobin than did Groups A and B. No significant between-group differences were observed regarding 90-day thromboembolic complications (there were none) or transfusions (there was only 1, in Group A), but the authors said “this study was likely underpowered for establishing meaningful comparisons concerning [those 2] outcomes.”
Although this study documented significantly lower total blood losses in patients who were managed with multiple doses of oral TXA postoperatively, additional studies are required to determine whether the 3-dose regimen is superior to the 2-dose regimen.
The evidence favoring tranexamic acid (TXA) for reducing surgical blood loss is ample and growing, but until now robust data were sparse regarding its efficacy in the setting of adolescent idiopathic scoliosis surgery. In the December 5, 2018 issue of The Journal of Bone & Joint Surgery, Goobie et al. report on a randomized, blinded, placebo-controlled trial showing that, in that population, TXA reduced perioperative blood loss by 27%, compared with blood loss in a placebo group.
Even with recent advances in scoliosis surgical technique, blood transfusions are common. And, because transfusions are associated with significant morbidity and mortality, limiting operative blood loss and reducing the need for transfusion have become focal points for orthopaedic surgeons.
In this Level-I trial, >100 patients between the ages of 10 and 18 years undergoing elective posterior instrumented spinal fusion were randomized to receive either TXA (infusion of a 50-mg/kg loading dose and a 10-mg/kg/h maintenance dose) or normal saline (delivered in the same way and dose) during surgery. The TXA group demonstrated an overall 27% reduction in cumulative blood loss and a 2-fold reduction in the percentage of patients with clinically relevant blood loss (defined as >20 mL/kg).
The cumulative effect of reduced blood loss was enhanced over time, with the positive effect of TXA being most evident in procedures lasting >4 hours. None of the patients in the TXA group required a transfusion or developed side effects such as thromboembolism or seizures.
In an interesting sidenote, the authors asked the participating orthopaedic surgeons, who were blinded to the randomization, to guess which group each patient had been assigned to by evaluating the relative ooziness of the surgical field. The surgeons guessed correctly 72% of the time.
Overall, these findings prompted the authors to conclude that “the use of TXA as part of a multimodal blood management strategy, as was employed in this study, should be considered the standard of care for patients undergoing surgery for adolescent idiopathic scoliosis.”
Minimizing perioperative blood loss during total knee arthroplasty (TKA) helps curtail the risks and costs of allogeneic blood transfusions. Currently, the most popular pharmacological approach to blood conservation is the antifibrinolytic agent tranexamic acid (TXA). But in a randomized trial published in the October 4, 2017 edition of The Journal of Bone & Joint Surgery, Boese et al. found that a similar and much less expensive compound, epsilon-aminocaproic acid (EACA), performed almost as effectively and just as safely as TXA in patients undergoing unilateral knee replacement.
Although the 98 patients in the study who received TXA averaged less estimated blood loss than the 96 patients who received EACA, no transfusions were required in either group, and there were no statistically significant or clinically relevant between-group differences in the change in hemoglobin levels. On the safety/complication side, there were no statistically significant between-group differences in any measured parameter, including postoperative serum creatinine levels or renal, bleeding, or thrombotic complications. However, there were 3 pulmonary emboli in the EACA group compared with only 1 in the TXA group. While that was not a statistically significant difference, “an observed difference of this magnitude could limit the usefulness of EACA in TKA,” the authors caution.
This study did not compare the current cost of the two compounds, but back in 2012, when the authors’ institution added antifibrinolytics to their blood management program, TXA cost $43/g, compared with $0.20/g for EACA. The cost differential is striking, even when you consider that TXA is at least 7 times more potent than EACA on a molar basis, so less of the former drug is required.
Boese et al. conclude that “TXA does not have superior blood conservation effects or safety profile compared with EACA in TKA,” but they cite a need for future equivalence, superiority, and noninferiority trials with these drugs.