Mechanical Thrombectomy (MT) has become the primary treatment for acute large vessel occlusion ischemic stroke (AIS-LVO) (1). Heparin, a commonly used anticoagulant, is primarily utilized in MT to prevent thrombus reformation and distal embolic events (2). However, in real-world MT practice, the use and dosage of heparin largely depend on the personal decisions of neurointerventionalists, leading to variations between different medical centers and a lack of standardized protocols (3, 4). Global practice patterns for periprocedural heparin use during endovascular stroke treatment vary widely, with the majority of interventionalists administering heparin via flush fluids and highly variable dosing, reflecting the absence of international consensus on optimal anticoagulation strategies (5). The main concern is that indiscriminate heparin administration may elevate the risk of hemorrhagic events. Consequently, there is an urgent need to identify a safe, effective, and practical strategy for heparin use during MT. At our stroke center, some neurointerventionalists have adopted a strategy of continuous intra-arterial heparin administration via high-pressure infusion throughout the MT procedure. Based on this institutional practice, we conducted a retrospective analysis of clinical data from patients with AIS-LVO who underwent MT at the Advanced Stroke Center of Chongqing University Central Hospital between August 2022 and January 2024. The aim of this study was to investigate the efficacy and safety of continuous intra-arterial infusion of heparin administration during MT.

In this retrospective analysis, we found that continuous intra-arterial infusion of heparin administration during mechanical thrombectomy (MT) was associated with a significantly higher proportion of patients achieving long-term functional independence compared to the non-heparin group. However, there were no significant differences between the two groups regarding the incidence of sICH, mortality rates and distal embolization events, additionally, regression analysis indicates that baseline NIHSS score at admission is an independent risk factor for favorable prognosis, while anticoagulation therapy administered during hospitalization may act as a protective factor. Therefore, our results suggest that continuous intra-arterial infusion of heparin administration during MT for LVO-AIS may offer greater efficacy and relative safety compared to no additional administering heparin. But, given the observational design, these findings should be interpreted as exploratory and hypothesis-generating rather than practice-changing. Further randomized controlled trials are needed to confirm these observations.

The role of periprocedural heparin during MT remains controversial. While heparin has traditionally been used to prevent catheter-related thrombosis and distal embolic events (6), recent high-impact evidence has raised concerns regarding its routine use. A 2024 systematic review and meta-analysis reported that periprocedural heparin administration was not associated with improved functional outcomes and may increase the risk of distal embolization, with a potential signal of harm in patients receiving bridging intravenous thrombolysis (7). In addition, registry-based and multicenter observational studies published in 2024 suggested increased risks of sICH or unfavorable outcomes associated with intravenous unfractionated heparin bolus during MT (8, 9). A subgroup analysis of the MOST randomized clinical trial in JAMA Neurology found that the addition of intravenous argatroban or eptifibatide to standard care for patients undergoing mechanical thrombectomy did not improve reperfusion or clinical outcomes (10). These data have contributed to a growing consensus that indiscriminate systemic anticoagulant therapy during MT may be harmful, it is crucial to balance the potential benefits of heparinization against the potential dose-dependent risks of bleeding complications.

It is important to note, however, that most contemporary studies have focused on systemic intravenous bolus administration of heparin. In contrast, the strategy evaluated in the present study involved continuous intra-arterial heparin administration as part of the catheter flushing system, rather than systemic bolus dosing. Recent international surveys have demonstrated substantial heterogeneity in real-world intraprocedural anticoagulation practices, particularly regarding heparin concentrations in flushing solutions and routes of administration, underscoring the lack of standardized protocols (5). Differences in administration route, dose exposure, and pharmacokinetics may partly explain the heterogeneity of reported safety and efficacy outcomes across studies.

Earlier studies from the pre-modern thrombectomy era, including post hoc analyses of the Multi MERCI (3) and TREVO 2 (2) trials, suggested that heparin use during endovascular treatment was not associated with increased hemorrhagic complications and might be linked to improved functional outcomes. Reperfusion can increase sICH risk (11), and thus heparin may act on microcirculatory thrombosis and reduce the risk of sICH (12). However, these studies were conducted with earlier-generation devices and were characterized by imbalances in bridging intravenous thrombolysis and procedural techniques. More recent randomized and post hoc analyses, such as those from the MR CLEAN-MED trial, have demonstrated increased hemorrhagic risk without functional benefit from periprocedural intravenous aspirin or heparin, reinforcing the need for caution when interpreting earlier findings (13).

The PROACT trial, a randomized controlled study of intra-arterial recombinant urokinase, compared higher (100 IU/kg bolus followed by 1,000 IU/h) and lower (2,000 IU bolus followed by 500 IU/h) heparin dosing regimens (14). The results indicated that heparin has a dose-dependent effect on recanalization and sICH. A retrospective analysis by Chinese researchers on heparinization during MT found that excessive heparinization might be associated with increased risks of sICH and distal embolization, as well as worse long-term outcomes, highlighting the need for further randomized controlled trials (15). This suggests that appropriate dosing and administration methods for heparin during MT are crucial. In this retrospective study, the heparin administration method used during MT did not result in a statistically significant difference in sICH risk between the groups.

Several studies have investigated the use of intravenous heparin during MT (3, 4, 16, 17). The incidence of sICH reported in these studies ranges from 5 to 12%, which is consistent with our study's findings. However, in terms of efficacy endpoints, the risk of sICH seems to be outweighed by the higher rates of favorable outcomes, suggesting that selective use of heparin during MT may be beneficial.

Distal embolization results from thrombus fragmentation during the thrombectomy process and is associated with poorer clinical outcomes. In our non-heparin group, four cases (9.1%) of distal embolization were recorded, which although not statistically different from the heparin group (1.9%, P = 0.143), was higher than previously reported rates (18). This may suggests that the appropriate use of heparin via high-pressure infusion may be more effective in preventing distal embolization. In addition, our multivariate regression analysis indicated that the use of direct aspiration may serve as a protective factor against sICH, we believe this could be attributed to the reduced endothelial irritation of the target vessel associated with direct aspiration. It is noteworthy that several infinite values were observed, and multiple 95% confidence intervals were excessively wide, which may be attributable to the limited sample size and event rates of our study.

In terms of baseline characteristics, the heparin group had a higher proportion of patients who received bridging therapy [43 (79.6%) vs. 27 (61.4%)], post-operative anticoagulation [24 (44.4%) vs. 9 (20.5%)] and direct aspiration thrombectomy [46 (85.2%) vs. 26 (59.1%)]. In contrast, the non-heparin group had a higher proportion treated with combined aspiration and stent retriever techniques [12 (27.3%) vs. 5 (9.3%)]. Although multivariable regression was performed, residual confounding cannot be excluded. Differences in patient presentation, stroke etiology, and operator preference may also have influenced treatment decisions and outcomes.

In addition, a higher baseline NIHSS score at admission was found to be independently associated with poor functional outcomes, which may reflect the established relationship between the severity of initial neurological deficits and clinical prognosis.

Interestingly, anticoagulation therapy initiated during hospitalization appeared to be associated with improved outcomes. This observation may be partially supported by recent studies advocating for early anticoagulation strategies following acute ischemic stroke (19, 20). This association, although not conclusive, may suggest a potential direction for future prospective investigation.

Overall, this study proposes the hypothesis that continuous intra-arterial infusion of heparin administration during MT may represent a feasible and relatively safe periprocedural strategy in selected patients. However, given the retrospective design, single-center setting, baseline imbalances, and limited sample size, the findings should be interpreted with caution. Prospective, standardized, and ideally randomized studies are required before any modification of clinical practice can be recommended.

Our study suggests that, in real-world practice, continuous intra-arterial infusion of heparin administration during MT for acute large vessel occlusion ischemic stroke may be safe and is associated with higher rates of favorable outcomes. Further prospective research is needed to validate these findings.