This study aimed to evaluate the feasibility and safety of using full dose anticoagulation-free peripheral VA-ECMO in lung transplantation. The findings suggest that peripheral VA-ECMO with reduced-dose heparin is a viable strategy, yielding favorable clinical outcomes—no deaths during follow-up, preserved graft function, and low postoperative complication rates. Importantly, there were no instances of PE or limb ischemia. This supports the hypothesis that full dose heparin-free peripheral VA-ECMO can be employed safely without increasing the risk of major thromboembolic complications. This study contributes novel insights into the use of full dose heparin-free peripheral VA-ECMO in lung transplantation. The key strength of this study lies in its single-center, retrospective design, which allowed for a consistent protocol and patient cohort, minimizing confounding variables often seen in multicenter studies. The absence of limb ischemia and　PE supports the safe implementation of peripheral VA-ECMO without exposing patients to anticoagulation-related risks. We preferentially used a 16-Fr femoral arterial cannula, which likely mitigated distal malperfusion while preserving adequate flows; notably, no distal limb perfusion complications occurred despite full dose heparin-free management. Our study also highlights that clinical outcomes such as survival rates, pulmonary complications, and graft function were comparable to those observed in patients with central VA-ECMO [10,11,12]. These results could provide an argument for the broader use of peripheral VA-ECMO, particularly in lung transplant recipients who may benefit from a less invasive and potentially safer strategy. Previous studies have shown that central VA-ECMO is an effective tool for providing circulatory support during lung transplantation via clamshell incision [10,11,12].

Previous study showed that re-do lung transplant recipients required a median of 1,600 mL (IQR 800–2,000 mL) of red blood cell transfusion, whereas in our full dose heparin-free peripheral VA-ECMO–supported cohort for re-lung transplant the median requirement was only 560ml [21]. Although direct inter-facility comparison is limited, these data suggest that our protocol may substantially reduce transfusion needs—consistent with other reports of full dose heparin-free ECMO strategies demonstrating decreased bleeding and transfusion requirements without compromising clinical outcomes [13, 22]. Previously, we published a case report of Veno-arterial extracorporeal membrane oxygenation without therapeutic anticoagulation for intra-operative cardiopulmonary support during lung transplantation [22], which demonstrated the safety of VA-ECMO without full anticoagulation. In our practice, we administer 5,000 U of unfractionated heparin before central VA-ECMO cannulation. Patients were not monitored with bleeding parameters such as ACT or aPTT during lung transplant procedure. To avoid thrombotic complication in the ECMO circuit, flow should be maintained at least 2.5 L/min during lung transplant procedure. If there is consistent reduction in circuit flow due to hypovolemia or peripheral vasodilation, repeat administering unfractionated heparin to reduce thrombogenicity is recommended. In addition, we recently reported the feasibility of VV-ECMO without systemic anticoagulation for respiratory failure patients [13], which has been shown to decrease blood transfusions and also reduce the number of required oxygenator exchanges. Furthermore, in both reports mentioned above, we made use of heparin-coated tubing and oxygenators to reduce bleeding and adverse thrombotic events. We believe this strategy is important for safely using VA or VV-ECMO without systemic anticoagulation; however, full dose heparin free peripheral VA-ECMO may increase the risk of thrombotic complications—such as circuit thrombosis, limb ischemia, and embolic stroke—which necessitates close monitoring (regular Doppler ultrasound and limb perfusion assessment) and the use of heparin-coated circuits or localized anticoagulation strategies when appropriate. Recently, innovations in ECMO circuit technology have decreased the pro-coagulant nature of ECMO. These include the use of heparin-coated tubing, centrifugal pumps and polymethylpentene oxygenators [6, 8, 9]. The advent of these new techniques has played a large role in being able to implement extracorporeal support without the use of systemic anticoagulation.

This study distinguishes itself by focusing specifically on peripheral VA-ECMO, which has been less widely studied. Unlike central VA-ECMO, peripheral VA-ECMO involves femoral venous and arterial cannulation, a technique that has been associated with easier insertion for re-do lung transplant or sparing sternum, making it particularly appealing for patients who may be at higher risk for bleeding or complications due to other comorbidities. Our findings that there were no PE complications in the peripheral VA-ECMO cohort suggest that this approach can be as safe as traditional central ECMO, if not more so, in reducing the potential for such adverse outcomes. Peripheral VA-ECMO can be performed with a smaller cannulation size and reduced risk of major vessel injury such as ascending aorta dissection, thus minimizing complications that could occur with central ECMO. This study also provides evidence that full dose heparin-free ECMO may help to address the growing concern of blood product use in high-risk populations. By reducing the need for anticoagulation, this strategy minimizes the risk of bleeding, which is often a major contributor to postoperative complications, prolonged ICU stays, and increased mortality in lung transplant recipients. Moreover, fewer transfusions are associated with improved kidney function, as excessive blood product transfusions can contribute to AKI in transplant patients. In our seven-case series, AKI occurred in 6 of 7 patients (86%), yet only 2 of 7 (29%) required dialysis, suggesting this approach may mitigate the progression to renal failure. These hypothesis-generating findings warrant confirmation in larger cohorts.

The safety of heparin-free ECMO is time-dependent and relates to cumulative thrombotic risk within the circuit, at cannula tips, and in native vessels. In our series, heparin avoidance was confined to short, intraoperative peripheral VA-ECMO runs (128–277 min), during which we observed no circuit thrombosis, embolic events, limb ischemia, circuit exchange, or low-flow instability. In lung transplantation, it is uncommon for operative time to exceed 24 h; within this window, we believe intraoperative peripheral VA-ECMO can be used safely without systemic heparin when adequate flows are preserved and surgical hemostasis is prioritized. Heparin-free VV-ECMO has been reported with no excess major thrombotic complications versus anticoagulated care (Kurihara et al., 2020), and VA-ECMO without routine systemic anticoagulation in the ICU setting was associated with fewer overall adverse events and lower blood product utilization without increased thrombosis or mortality (Wood et al., 2020). Taken together, these observations suggest that heparin-free support is reasonable for short intraoperative runs under vigilant monitoring, while acknowledging that patients with prothrombotic states (e.g., HIT), intracardiac stasis/poor pulsatility, or non–heparin-coated circuits should not be managed with a fully heparin-free approach and warrant earlier transition to systemic anticoagulation.

Based on these data, our institution favors a limited-application policy rather than universal use. Specifically, heparin-free intraoperative peripheral VA-ECMO will be considered for re-do lung transplant candidates in whom bleeding risk is expected to predominate. Candidate indications include (i) anticipated diffuse adhesion-related bleeding (e.g., re-do cases with dense pleural or perihilar adhesions, prior intrapericardial cardiac procedures, or prior thoracic radiation/operations), (ii) pre-existing high bleeding risk (active antiplatelet therapy that cannot be interrupted, known coagulopathy or platelet dysfunction), and (iii) a history of recurrent major bleeding on systemic anticoagulation. Exclusions/relative contraindications include prothrombotic states (e.g., heparin-induced thrombocytopenia), cardiac failure with intracardiac stasis, inability to sustain circuit flows ≥ 2.5 L/min after correction of reversible factors, non–heparin-bonded circuits and anticipated prolonged support beyond the intraoperative period.

Despite the promising findings, this study has several limitations. First, the retrospective design introduces inherent biases, such as selection bias, which could affect the generalizability of the results. In addition, our cohort did not include patients with reduced left ventricular systolic function; therefore, the safety of full dose heparin-free peripheral VA-ECMO may not generalize to populations with low EF, in whom the risk of LV distension or thrombus formation may be higher when anticoagulation is minimized.　Additionally, while the sample size was sufficient for initial conclusions, larger, multicenter studies are needed to further validate the safety and effectiveness of full dose heparin-free peripheral VA-ECMO in a broader patient population. Another limitation is the absence of long-term follow-up data regarding chronic rejection, graft survival, and other late complications, which would provide a more comprehensive understanding of the long-term impact of this approach. Additionally, the study was conducted at a single center, and results may vary in institutions with different protocols, patient demographics, or institutional expertise.