Discussion
The indications for the use of TXA have moved beyond acute resuscitation to routine use in elective and semi-urgent procedures. Driven primarily by research in the orthopedic literature, proposed benefits include decreased perioperative bleeding, decreased transfusion requirements, and a similar safety profile related to VTE.12 13 However, there has been little scientific evidence demonstrating safety in a high-risk, injured population.
The purpose of this study was twofold. First, we sought to determine if the use of TXA in urgent surgical cases affected the risk of VTE when used in an acutely injured population. Second, we sought to validate whether TXA use in this population decreased the overall transfusion requirements from semi-urgent orthopedic procedures.
The systemic response to injury leads to many physiological alterations, including a transient hypercoagulable state immediately following injury.14 15 Overall, the rates of VTE were very low (5.76%) and there was no significant association between TXA use and odds of VTE. Although the elective orthopedic literature to date has not identified an association between intraoperative TXA and VTE, prospective trials evaluating the effectiveness of TXA use in this fashion excluded patients deemed high VTE risk, and those with VTE history.4 6 7 16 17 This study addressed this gap with a focus exclusively on high-risk, injured patients. Although overall episodes of VTE were increased in the TXA+ group (n=14, 7.5%) compared with the CONTROL group (n=9, 4.5%), this did not translate into a statistical difference. The modern, and aggressive anticoagulation regimens render VTE events uncommon and may be effective in lessening any potential adverse effects of TXA use in hypercoagulable populations. Considering the low incidence of VTE in this study population, the available cohort likely resulted in too little power to detect a difference, if one existed. Additionally, this center did not routinely screen for DVT in asymptomatic patients, potentially resulting in failure to identify asymptomatic VTEs.
The relationship between TXA use and transfusion requirements was more complex. The mechanism by which TXA is theorized to reduce blood loss is via inhibition of fibrinolysis, allowing stabilization of early clot. TXA usage in trauma populations has been well-studied but has not demonstrated an association between TXA use and reductions in transfusion volume.1 2 18 This study similarly noted no decrease in likelihood of transfusion with prophylactic TXA administration. Rather the TXA+ group had a significant increase in transfusion events.
The expanded understanding of trauma coagulopathy suggests that over 80% of trauma patients are in a hypercoagulable state, and <10% have hyperfibrinolysis.2 19 Hyperfibrinolysis, as a component of acute traumatic coagulopathy typically, marks the early postinjury period in the severely injured patient20 . Most modern studies examining the effects of TXA have only supported administration in the first 3 hours following injury. There is little support for inhibition of fibrinolysis remote from injury.2 21 Therefore, the use of TXA in semi-urgent procedures multiple days following injury would not be supported by the modern injury literature. Furthermore, trauma patients are at inherently high risk for VTE.11 15 Increasingly, research studies caution against the empiric use of TXA, as it may increase VTE events.22–24
Our data do not support the prophylactic use of TXA to decrease PRBC transfusion rates. There were increased odds of transfusion, both intraoperatively and over the entire hospitalization, in the TXA+ group. Why this is the case is unclear. All patients received TXA empirically prior to start of the case, so there was no relationship between intraoperative bleeding and administration. The statistical modeling accounted for factors that are likely to increase blood loss or transfusion such as injury severity, transfusion in the first 24 hours following injury, and early surgical therapy as used in the propensity matching. The generalized linear model controlled for proximal fracture site, tourniquet use, need for damage control surgery, and total number of surgeries required—all of which can contribute to increased or decreased transfusion requirements. Despite these adjustments, TXA+ patients were six times more likely to be transfused than patients in the CONTROL group. There are likely other factors at work contributing to increased blood utilization in the TXA+ group. Regardless, TXA provided no protection from transfusion. This represents an interesting area for follow-up study.
This study has limitations. First, the retrospective nature limits the ability to determine causation, and we can only identify associations. Second, our center does not routinely screen every patient for VTE. Current practice is to evaluate patients based on concerning symptomatology, which ultimately will lead to a lower incidence of DVT and possibly inaccurate representation of the true VTE rate. Routine screening has been associated with increased incidence of DVT, but not necessarily better quality outcomes.25 For this reason, our center has not adopted a routine screening practice. Lastly, the administration of TXA during orthopedic and spine surgeries was not protocolized but given at the discretion of the operative surgeon. This could induce bias, as surgeons may choose to give TXA in cases where predicted blood loss is higher.
Another important limitation is in the construction of the study groups. The CONTROL group represented an earlier time period in which TXA was not empirically used. The TXA+ study group was a later time frame. Although the difference in time was only 2 years, this chronological difference may have introduced variations in practice which could account for some differences in transfusion volumes. Additionally, the existing number of patients in the study time period limited the cohort size, resulting in the potential that the study was underpowered to detect VTE.