Posterior lumbar interbody fusion (PLIF) is a surgical method for the treatment of lumbar spondylolisthesis, lumbar spinal stenosis, and lumbar disc herniation. It has the advantages of mature technology, good clinical efficacy, and high fusion fixation efficiency (1). The anatomical structure of the spine is a spongy vertebral body, with a rich blood supply and a weak venous plexus. During PLIF, significant blood loss may occur, increasing the postoperative incidence rate and prolonging the clinical recovery time (2–4). In addition, most of the patients receiving PLIF are older adults, with poor hematopoietic function and extensive recovery time. Substantial blood loss is very likely to lead to serious complications such as myocardial infarction, cerebral infarction, pulmonary embolism, and severe anemia, requiring blood transfusion. Blood transfusion will not only increase the wound infection rate after surgery but may also cause many complications, such as hepatitis, AIDS, and other infectious diseases, as well as fever, vascular embolism, and delayed healing or even non-healing of wounds (5).

To reduce perioperative bleeding and avoid the adverse consequences of blood transfusion, antifibrinolytic drugs have been widely used (6), with tranexamic acid (TXA) being the most extensively used (7). TXA is an artificially synthesized amino acid derivative, the hemostatic effect of which is mainly related to the occupation of functional targets on fibrinolytic enzymes and fibrinogen (FIB). It stops the binding of fibrinolytic enzymes and fibrin, reduces the decomposition of fibrin, and ultimately plays a hemostatic role (8). Since the first application of TXA in total knee arthroplasty in 1995, extensive usage and significant research have confirmed that this drug can reduce perioperative blood loss and transfusion needs (9). However, we note that there is a pressing requirement for an efficient and safe alternative drug in clinical work due to temporary drug shortages of TXA in hospitals or its association with perioperative epilepsy and postoperative stroke during cardiac surgery (10–12). The mechanism of action of epsilon-aminocaproic acid (EACA) is similar to that of TXA. Although studies have shown (13) that TXA and EACA have similar hemostatic effects in the perioperative period of intertrochanteric fractures of the femur, there are significant differences between spinal surgery and limb surgery. Therefore, we adopted a retrospective cohort study to compare the clinical effects of intravenous application of EACA and TXA on reducing perioperative blood loss, observe the effectiveness and safety of the two drugs, and explore whether EACA can serve as a substitute for TXA, all during PLIF surgery.

PLIF is a common procedure for lumbar degenerative diseases; however, it is frequently associated with considerable perioperative blood loss (17). Wang et al. reported blood loss during PLIF to be as high as 1,260 mL, underscoring the significant perioperative risk posed by hemorrhage (18). TXA, a widely adopted antifibrinolytic agent and included in the WHO’s essential medicines list since 2011, has demonstrated efficacy in reducing surgical bleeding (19). However, its use is accompanied by concern regarding adverse effects, such as seizures, stroke, and allergic reactions (7). These risks highlight the need for safer alternative antifibrinolytic agents. EACA, which shares a similar mechanism of action as TXA but does not cross the blood–brain barrier, is associated with a lower risk of central nervous system-related adverse events, like seizures. Although EACA has an established record in cardiac surgery, its application in spinal surgery remains underexplored. Thus, the present study was designed to evaluate the hemostatic efficacy and safety of EACA in the context of PLIF.

Our findings indicate that intravenous usage of EACA and TXA yield comparable hemostatic outcomes. No significant differences were observed between the two groups in terms of total blood loss, total red blood cell loss, intraoperative bleeding, or postoperative drainage volume. When transfusion rate was considered as a clinical endpoint, 11 patients (11.70%) in the TXA group and 8 patients (9.30%) in the EACA group received transfusions, a difference that was not statistically significant (p > 0.05). This suggests that both agents are similarly effective in minimizing blood loss and transfusion requirements. EACA, a lysine analog antifibrinolytic, has been well studied in cardiac settings and is recognized for its favorable safety profile (20). Although TXA remains a first-line medication in many orthopedic applications, EACA has garnered increasing interest as a potential alternative for reducing blood loss in major orthopedic procedures (21).

Given the limited evidence regarding EACA's use in PLIF, we referred to studies within general orthopedic surgery. Our results align with previous comparative reports. For instance, Bradley et al. found no significant differences in hematologic outcomes, complications, or length of stay between patients receiving EACA and those receiving TXA in joint arthroplasty (22). Similarly, Riaz et al. reported comparable operative times and thromboembolic rates between the two agents (23). A randomized controlled trial involving 194 total knee arthroplasty patients noted that although calculated blood loss was higher in the EACA group, transfusion rates did not differ significantly between the EACA and TXA groups, reinforcing the notion of clinical comparability (24).

Orthopedic surgeries, including PLIF, are associated with non-negligible risks of deep vein thrombosis (DVT), attributable to surgical trauma, prolonged immobilization, and the use of antifibrinolytics, which may tilt the hemostatic balance toward a prothrombotic state (7). In our study, DVT was observed in 10 (11.62%) patients in the EACA group and 17 (18.09%) in the TXA group; this difference did not reach statistical significance (p = 0.226), suggesting a comparable safety profile in terms of thrombotic risk. This finding is consistent with that of Zhou et al., who also reported no significant difference in thrombotic events between the EACA and TXA groups (10). Nonetheless, the observed numerical increase in DVT events associated with TXA warrants attentive monitoring and further investigation.

Although our study demonstrated comparable hemostatic efficacy and a similar overall safety profile between EACA and TXA during PLIF surgery, it is important to acknowledge the specific safety concerns associated with EACA that are documented in the literature and drug labeling. EACA has been associated with upper urinary tract bleeding, which may lead to ureteral or renal pelvic clot obstruction and acute kidney injury—particularly when hematuria originates from the upper tract. Therefore, caution is advised in such scenarios, unless the benefits clearly outweigh the risks (25). In addition, cases of myopathy and rhabdomyolysis have been reported, which can progress to myoglobinuria and renal failure, especially with prolonged use. Monitoring of creatine kinase (CK) is recommended in prolonged therapies to mitigate this risk (26). Thromboembolic events, though rare, including intracardiac thrombosis and pulmonary embolism, have been observed, particularly in cardiac surgery settings (27). Rapid intravenous administration of EACA may also induce hypotension, bradycardia, or arrhythmias, underscoring the importance of slow infusion and adequate dilution (28). Other rare hematologic and neurologic adverse effects, such as agranulocytosis, leukopenia, seizures, and stroke, have been listed in labeling, though causality remains uncertain in many cases (29). These potential risks highlight the need for careful patient selection, appropriate dosing, and vigilant monitoring when using EACA, especially in populations with underlying renal or cardiac comorbidities.

Regarding the observed statistically significant differences in certain laboratory values—specifically red blood cell distribution width (RDW), TP, and INR—we interpret these findings with caution due to their limited clinical relevance. The slight elevation in postoperative INR in the TXA group (1.14 ± 0.13 vs. 1.06 ± 0.14 in the EACA group) and higher TP values (59.36 ± 6.73 vs. 56.17 ± 7.83 g/L) fell within normal physiologic ranges and did not correlate with clinical outcomes such as bleeding or thromboembolic events. Moreover, after adjusting for multiple comparisons using the Bonferroni method, these differences lost statistical significance, suggesting that they may represent random variations rather than true pharmacologic effects (8, 16). Although the incidence of thrombotic events was not statistically significant (11.62% in the EACA group vs. 18.09% in the TXA group, p = 0.226), the observed numerical trend warrants thoughtful consideration. This pattern is consistent with previous reports indicating that TXA, with its higher antifibrinolytic potency and longer half-life, may be associated with a modest increase in prothrombotic risk in certain surgical populations (10, 11). Therefore, while our study did not demonstrate a significant difference in thrombotic complications, the trend underscores the need for heightened clinical vigilance and further investigation through larger, adequately powered trials to thoroughly evaluate the safety profiles of both agents.

This study has several limitations that should be taken into consideration: (1) As a retrospective study, the results are susceptible to selection bias and unmeasured confounding factors. Although propensity score matching was applied to improve intergroup comparability and all analyses were adjusted for measurable baseline variables, the non-randomized design precludes causal inference. In addition, the lack of blinding may have influenced outcome assessment, particularly for subjective endpoints. Although we made every effort to ensure data completeness through rigorous extraction and validation from medical records, missing or inconsistently documented parameters cannot be entirely ruled out. (2) Although the Gross and Nadler equations are well validated and widely applied in estimating perioperative blood loss, they remain surrogate models rather than direct measurements. Thus, some degree of imprecision in quantitative blood loss assessment is inevitable. (3) The optimal dose and timing of EACA and TXA during spinal fusion surgery have not been standardized. Our results are based on a specific regimen, and the generalizability to alternative protocols requires further investigation. Consequently, the findings should be interpreted as exploratory, and validation through prospective randomized controlled trials is strongly recommended.

Based on the findings of this retrospective study, intravenous EACA demonstrates comparable efficacy to TXA in reducing perioperative blood loss and transfusion requirements in patients undergoing posterior lumbar interbody fusion surgery. However, although not statistically significant, the numerically higher incidence of thrombotic events associated with TXA merits serious attention. These results suggest that EACA may represent a viable alternative to TXA in this surgical context, but broader clinical recommendations should await validation from larger, prospective, and ideally randomized controlled trials that are sufficiently powered to clarify the safety profile—particularly regarding thrombotic risk—of both antifibrinolytic agents.