Preoperative Antifibrinolytics Reduce Transfusions After Vascular Surgery

Mitigating Hemorrhagic Risk in High-Stakes Vascular Revascularization

Major vascular interventions carry an inherent risk of significant intraoperative blood loss and subsequent coagulopathy, a clinical state where the blood's ability to form stable clots is impaired by the depletion of clotting factors and platelets. While blood product transfusions are often necessary for resuscitation, they are associated with increased risks of myocardial infarction and death [1]. Antifibrinolytic agents, which work by inhibiting plasmin-mediated lysis (the enzymatic breakdown of fibrin clots that can lead to uncontrolled oozing), have become standard in several surgical specialties but remain underutilized in vascular procedures due to a historical lack of specific data [2]. Recent large-scale trials in noncardiac surgery have demonstrated that tranexamic acid can reduce bleeding outcomes, though concerns regarding noninferiority for cardiovascular events persist [3]. Clinicians must balance these benefits against the potential for thrombo-inflammation, the complex interaction between coagulation and inflammatory pathways that can drive adverse events in cardiovascular patients [4]. A new study now evaluates whether preoperative administration of these agents can safely bridge this gap in major vascular revascularization.

Evaluating Antifibrinolytic Use in Major Revascularization

The researchers conducted a retrospective analysis of 674 cases involving adult patients across a multi-hospital healthcare system between January 2017 and June 2024 to determine if preoperative antifibrinolytic agents could mitigate the need for postoperative transfusions. The study population had a mean age of 68.6 ± 10.8 years, with a demographic composition that was 67.4% male and 88.1% White. The analysis focused on elective, index major abdominal revascularization procedures, including open abdominal aortic aneurysm repair, mesenteric revascularization, and aortoiliac revascularization, as well as lower extremity revascularization procedures such as open bypass. These high-risk interventions are frequently complicated by significant blood loss due to the extensive dissection and systemic anticoagulation required, making them a critical area for investigating blood conservation strategies.

The intervention was defined as the preoperative administration of an antifibrinolytic agent, specifically tranexamic acid (TXA) or epsilon-aminocaproic acid (EACA), within 60 minutes of the operative start time as recorded in anesthesia logs. These agents function by inhibiting intra-operative plasmin-mediated lysis, a process where the enzyme plasmin breaks down fibrin clots and prevents stable hemostasis. By stabilizing these clots, clinicians aim to reduce the volume of blood lost during the most invasive portions of the revascularization, potentially avoiding the systemic inflammatory response often triggered by massive hemorrhage. Of the total cohort, 213 patients (31.6%) received these agents preoperatively, allowing for a comparison against those who did not receive the treatment.

The primary outcome measured was the total number of blood product transfusions, including packed red blood cells, fresh frozen plasma, platelets, or cryoprecipitate, administered within 5 postoperative days. To address concerns regarding the prothrombotic potential of these medications, the researchers tracked several safety outcomes. These included in-hospital seizures, venous thromboembolism events (VTE) such as deep venous thrombosis and pulmonary embolism, and arterial thrombosis, which encompassed stroke and bypass thrombosis. Additionally, the study monitored for postoperative bleeding complications to ensure that the reduction in transfusions did not correlate with an increase in other adverse surgical events, providing a comprehensive view of the risk-to-benefit ratio for the practicing vascular surgeon.

Significant Reduction in Postoperative Transfusion Requirements

The primary analysis of the 674 cases revealed that 213 patients (31.6%) received preoperative antifibrinolytic agents, demonstrating a significant shift in transfusion requirements for this subgroup. Among this treated group, only 36 patients (16.9%) required a blood transfusion by the fifth postoperative day. For those who did require transfusion, the volume of blood products remained relatively low, with patients receiving a median of 2 products per person, with an interquartile range (IQR) of 1 to 2 products. These figures highlight a controlled transfusion requirement in the context of high-risk vascular procedures when antifibrinolytic therapy is initiated within 60 minutes of the operative start time, suggesting that early intervention may stabilize the coagulation cascade before significant depletion occurs.

The researchers found that preoperative antifibrinolytic administration was significantly associated with a reduction in the number of blood products transfused within five postoperative days, yielding an adjusted incidence rate ratio (aIRR) of 0.57 (95% CI [0.34 to 0.98], p-value=.04). This indicates a 43 percent reduction in the expected number of transfusions for patients receiving the intervention compared to those who did not. This finding is particularly relevant for clinicians managing the high costs and potential complications, such as myocardial infarction or increased mortality, associated with blood product administration in the vascular surgery suite, where minimizing allogeneic blood exposure is a primary goal of perioperative care.

To ensure the robustness of these results, the study utilized a multivariable negative binomial regression, which is a statistical model specifically designed to analyze count data while accounting for overdispersion (a situation where the variability in the data is higher than expected, common in surgical transfusion records). This model analyzed the association between antifibrinolytic use and transfusion rates while adjusting for clinically significant covariates chosen a priori, or pre-selected variables known to influence surgical outcomes. Furthermore, the analysis incorporated variance clustering by surgeon, a technique that accounts for the statistical correlation between patients treated by the same physician to ensure that individual surgical techniques or preferences did not skew the overall findings, thereby increasing the generalizability of the results to broader clinical practice.

Safety Profile and Thrombotic Risk Assessment

The clinical utility of antifibrinolytic agents in major vascular surgery for peripheral artery disease is often weighed against the potential for prothrombotic complications, particularly in a patient population already burdened by systemic atherosclerosis. These high-stakes interventions carry significant risks of intraoperative blood loss and resultant coagulopathy, a state where the blood's clotting mechanism is impaired. While blood product transfusions are a standard response to surgical hemorrhage, they remain limited in supply, costly to healthcare systems, and are clinically associated with an increased risk of myocardial infarction and death. Consequently, establishing the safety of preoperative tranexamic acid or epsilon-aminocaproic acid is essential for their adoption as a standard of care. In this study, the researchers found that rates of venous thromboembolism were nearly identical between groups, with N=2 (0.9%) in the antifibrinolytic group compared to N=5 (1.1%) in the non-antifibrinolytic group (p-value=.86). Furthermore, there were no recorded instances of in-hospital strokes in either cohort.

Concerns regarding the impact of antifibrinolytics on graft patency were addressed through the analysis of bypass thrombosis, which is the sudden occlusion of a newly created vascular conduit that can lead to acute limb ischemia. The study found that bypass thrombosis occurred in N=7 (3.3%) of the antifibrinolytic group versus N=11 (2.4%) of the non-antifibrinolytic group, a difference that did not reach statistical significance (p-value=.7). Similarly, the incidence of bleeding complications remained stable across both cohorts, occurring in N=3 (1.4%) of patients receiving antifibrinolytics and N=6 (1.3%) of those who did not (p-value>.9). Notably, postoperative seizures, a known potential side effect of high-dose antifibrinolytic therapy, were only observed among patients who did not receive preoperative antifibrinolytic agents (N=2). These data suggest that the administration of these agents within 60 minutes of the operative start time does not significantly increase the risk of major thrombotic or neurological adverse events, supporting their potential inclusion in standard preoperative protocols for major vascular surgery.

References

1. Coccolini F, Shander A, Ceresoli M, et al. Strategies to prevent blood loss and reduce transfusion in emergency general surgery, WSES-AAST consensus paper. World Journal of Emergency Surgery. 2024. doi:10.1186/s13017-024-00554-7

2. Beverly A, Ong G, Kimber C, et al. Drugs to reduce bleeding and transfusion in major open vascular or endovascular surgery: a systematic review and network meta-analysis. Cochrane Database of Systematic Reviews. 2023. doi:10.1002/14651858.cd013649.pub2

3. Devereaux P, Marcucci M, Painter T, et al. Tranexamic Acid in Patients Undergoing Noncardiac Surgery. New England Journal of Medicine. 2022. doi:10.1056/nejmoa2201171

4. D’Alessandro E, Becker C, Bergmeier W, et al. Thrombo-Inflammation in Cardiovascular Disease: An Expert Consensus Document from the Third Maastricht Consensus Conference on Thrombosis. Thrombosis and Haemostasis. 2020. doi:10.1055/s-0040-1708035