Prediction, incidence, and outcomes of massive transfusion during lung transplantation

Introduction

Lung transplantation (LT) is the definitive therapy for patients with end-stage pulmonary disease, offering the only meaningful chance of long-term survival when medical management fails (1). Over the past decades, the volume of lung transplants and post-transplant survival rates have steadily increased worldwide (2,3), reflecting advances in surgical technique, perioperative care, and donor management. Nevertheless, LT remains a highly complex procedure often complicated by substantial intraoperative hemorrhage and the need for blood transfusion support. Managing coagulopathy and blood loss during LT is a critical challenge for surgeons and anesthesiologists, particularly in certain high-risk scenarios such as re-transplantation, extensive pleural adhesions from prior chest surgeries, or diseases like sarcoidosis that can cause dense intrathoracic scarring (4). The use of cardiopulmonary bypass or extracorporeal membrane oxygenation (ECMO) during transplant, while sometimes necessary for unstable patients, may further contribute to coagulopathy and bleeding. Prolonged ECMO, in particular, has been associated with liver ischemia that may further complicate an ensuing hemorrhage perioperatively (5). As a result, perioperative transfusion of allogeneic blood products is common in LT and has been widely associated with adverse outcomes such as severe primary graft dysfunction (PGD) and increased early mortality (3). Despite modern improvements in hemostatic management, lung transplant surgery is still frequently accompanied by significant blood loss and transfusion requirements.

Multiple studies underscore the considerable blood product utilization during LT. For an average lung transplant case, patients often require several units of blood; for example, in one series, the mean transfusion per transplant was approximately 3–4 units of packed red blood cells (RBCs), along with associated plasma and platelets as needed (3). Targeted transfusion strategies (guided by point-of-care coagulation tests and tailored to patient needs) have been explored to minimize unnecessary blood product use (6-8). Nevertheless, even with meticulous care, a subset of lung transplant recipients experience massive hemorrhage that necessitates massive transfusion (MT), typically defined as transfusion of ≥10 units of RBCs within a 24-hour period (often intraoperatively) (3). This scenario represents an extreme on the spectrum of perioperative bleeding, and it remains a major perioperative concern despite advances in surgical and anesthetic techniques.

Patients requiring such large-volume transfusions during LT represent a particularly vulnerable group. These individuals often develop hemodynamic instability and coagulopathy intraoperatively, and they face elevated risks of perioperative complications and mortality. Large transfusion volumes can precipitate transfusion-related complications like transfusion-related acute lung injury (TRALI) and exacerbation of PGD, compounding the direct effects of hemorrhagic shock. Clinical analyses have shown that lung transplant recipients with severe bleeding or MT have markedly worse outcomes than those with only mild-to-moderate bleeding. In one retrospective study, the incidence of severe PGD (grade 3 at 72 hours post-transplant) was about six-fold higher in patients with severe intraoperative bleeding compared to those with lesser bleeding, and 30-day mortality in the high-bleeding group reached 7% vs. 0.6% in others (9). Similarly, another cohort study observed that patients who underwent MT had approximately threefold higher 30-day mortality (13% vs. 4%) and significantly reduced longer-term survival relative to those not requiring MT (3). These findings highlight that excessive transfusion is a proxy for complex, high-risk cases and is associated with markedly poorer postoperative outcomes.

Understanding this unique subset of LT patients is essential for improving care. By identifying and addressing the preoperative risk factors and profiles of individuals prone to massive bleeding, clinicians can implement targeted strategies—such as preemptive use of antifibrinolytic therapy, refined surgical approaches for challenging re-entry cases, or ensuring the immediate availability of specialized hemostatic adjuncts–to minimize blood loss. In recent years, researchers have explored machine-learning and statistical risk models to anticipate transfusion needs during surgery (10). The ability to predict an MT scenario—even to a rough degree—before or early in surgery could enable the transplant team to mobilize resources and apply bleeding mitigation strategies proactively. Early identification of high-risk cases might also facilitate informed consent discussions and targeted interventions (for example, positioning cell salvage devices or dose-adjusting anticoagulation protocols). Although previous studies have reported that low body mass index (BMI) and baseline hematocrit (Hct) are associated with the risk of intraoperative MT, a systematic evaluation of the homogeneous Chinese Han population is still lacking. This study fills the gap in this population and provides targeted guidance for preoperative risk assessment.

Despite extensive literature on blood transfusion in LT in general (11-13), relatively few studies have focused specifically on the cohort of patients who receive intraoperative MT. Consequently, important questions remain about the incidence and outcomes of MT in the current era of lung transplant, as well as which perioperative factors most strongly drive the need for massive blood replacement. This retrospective study was performed to investigate the incidence, risk factors, and prognosis for patients who received MT, defined as the transfusion of ≥10 units of allogeneic RBC during LT surgery. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-857/rc).

Methods

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional review board (IRB) of The Second Affiliated Hospital of Zhejiang University School of Medicine (No. 2022-0352), and no executed donor organs were used for these patients. The requirement for informed consent was waived by the IRB based on the retrospective nature of the study. All adult (age ≥18 years) patients undergoing LT between February 2020 and March 2022 in our institution were identified. Patients who underwent combined organ transplantation or LT combined with other surgeries were excluded from analysis. Retransplantation was also excluded.

LT was performed under clamshell incision of the fourth intercostal space. In case of bilateral LT, the poorer side was implanted first. Intraoperative and postoperative care followed standard clinical protocols. All patients received general anesthesia with a double-lumen endobronchial tube. Intraoperatively, patients were monitored by invasive blood pressure, central venous pressure, pulmonary artery pressure, cardiac index, systemic vascular resistance, and transesophageal echocardiography. Vasopressors, inotropes were administered as appropriate. The application of ECMO was decided by the surgeon and anesthesiologist together. Unfractionated heparin was used as anticoagulant agent for ECMO. A bolus dose of 50–100 IU/kg was administered during ECMO cannulation, followed by hourly monitoring to achieve a target activated clotting time (ACT) range of 160–220 s. After LT, patients were transferred to the intensive care unit (ICU), where they were consecutively monitored and managed by a multidisciplinary team.

Intraoperative transfusion of blood products was managed by the anesthesiologist. Cell salvage was used routinely. RBC was transfused when hemoglobin was <8.0 g/dL. However, a relatively higher transfusion trigger was considered based on patient’s hemodynamic status, blood loss, and surgical complications. In this study, MT was defined as intraoperative transfusion ≥10 units of allogeneic RBCs. Laboratory testing, including thromboelastography, platelet count, prothrombin time, activated partial thromboplastin time, and fibrinogen, was utilized to support the transfusion decision. Fresh frozen plasma (FFP), platelets, antifibrinolytics, fibrinogen, and recombinant factor VIIa were given as necessary to correct hemostasis. Transfusion of blood components was recorded.

Data were prospectively collected and retrospectively extracted, including demographics, pretransplant comorbidity, etiology of lung disease, and laboratory values. Intraoperative variables included surgery duration, type of ECMO support, the use of vasopressors or inotropes, and urine output. Donor characteristics included donor age, gender, oxygen index, and ischemia time. Postoperatively, the immediate Hct after surgery, requirement of continuous renal replacement therapy (CRRT) within 1 month, ECMO support duration, mechanical ventilation time, ICU days, grade 3 PGD at 72 hours, and survival were recorded.

Statistical analysis

Patients were allocated into the MT group or the non-MT group. Normally distributed data were expressed as a mean and standard deviation (SD), while non-normally distributed data were expressed as median (interquartile range). Categorical variables were expressed as percentages. Student’s t-test, Mann-Whitney U test, Chi-squared test, or Fisher’s test was conducted as appropriate to describe the differences of perioperative characteristics between the MT and the non-MT groups. Univariate and multivariate analyses were performed by logistic regression to evaluate preoperative risk factors for MT. The cut-offs were determined by the Youden index. Prediction accuracy of using the risk factors was evaluated using the area under the receiver operating characteristic curve (AUC). Odds ratios (ORs) with 95% confidence intervals (CIs) and P values were reported. Recipient survival was analyzed using Kaplan-Meier survival method and differences between groups were compared with the log-rank test. Cox survival analysis was used to identify factors associated with recipient survival. Statistical significance was considered as P value <0.05. All statistical analyses were performed using IBM SPSS version 22 (IBM, Armonk, NY, USA).

Results

During the study period, 149 adults underwent LT at The Second Affiliated Hospital of Zhejiang University School of Medicine and 144 were included in the analysis (Figure 1). The mean age of the study population was 56.6±11.8 years. Patients were predominantly male (81.9%). The most common etiology of lung disease was restrictive lung disease (55.4%), followed by chronic obstructive pulmonary disease (COPD) (25.0%) and pneumoconiosis (12.5%) (Table 1).

Figure 1 Flowchart. LT, lung transplantation; MT, massive transfusion.

Of 144 recipients, 75 (52.1%) patients received RBC transfusion during LT surgery and 15 (10.4%) patients received RBC ≥10 units. Median RBC transfusion in the MT group was 3,000 (interquartile range, 2,400–3,900) mL, and the maximum was 5,600 mL. Units of transfused RBC in the MT group accounted for 43.2% of total RBC transfusion (240/556 units) used for all patients during the study period (Figure 2).

Figure 2 The number of patients (bars) and the trend of cases (line) on different RBC transfusion volumes. MT patients were marked as grey bars. MT, massive transfusion; RBC, red blood cell.

To investigate the preoperative predictors of MT, we compared recipient and donor characteristics between the MT and the non-MT groups. The MT group was associated with decreased BMI and lower preoperative Hct (Table 1). Multivariable analysis included factors with P<0.1 in the univariate analysis, showing that BMI and the preoperative Hct were independently predictive for MT (P<0.05, Table 2). The cut-offs for BMI and Hct were 24.7 kg/m² and 21.9%, respectively. As BMI or Hct increased, the risk of MT significantly decreased as shown in Figure 3. To detect the prediction accuracy of using the two risk factors, the AUC was calculated. The AUC was 0.81 (95% CI: 0.72–0.90; P<0.001), indicating a good predictability.

Figure 3 The relationship between predicted probability of MT and pretransplant BMI (A) and Hct (B). Grey areas represent 95% CIs. BMI, body mass index; CI, confidence interval; Hct, hematocrit; MT, massive transfusion.

In regards of the intraoperative and postoperative variables, MT was associated with increased surgery duration, increased FFP, and platelet transfusion as shown in Table 3. And MT was related to decreased urine output significantly (Table 3). The intraoperative application of ECMO and administration of vasopressors or inotropes were comparable between groups. The incidence of CRRT in the MT group was significantly higher than that in the non-MT group (P<0.001). After adjustment by other variables (factors with P<0.1 in the univariate analysis, including gender, diabetes mellitus, Hct, surgery duration, type of ECMO support, FFP, and platelet transfusion) in logistic regression analysis, MT was still an independent risk factor (OR =8.05; 95% CI: 2.45–26.52; P=0.001) for CRRT. In addition, the MT group was related to prolonged mechanical ventilation time and increased incidence of grade 3 PGD at postoperative 72 hours. The postoperative ICU stay was comparable between the MT and the non-MT groups (Table 3).

In our cohort, 30- and 90-day recipient mortality were 53.3% and 60.0% in the MT group, significantly higher compared with those in the non-MT group (14.7% and 25.6%, P<0.001; Figure 4). Cox survival analysis showed that MT was an independent risk factor [hazard ratio (HR) =5.13; 95% CI: 2.22–11.84; P<0.001] for 30-day mortality.

Figure 4 Patient survival. Patient survival in the MT group was significantly lower compared with that in the non-MT group. MT, massive transfusion.

Discussion

In this study, our main findings were as follows: (I) up to 10.4% of LT recipients received MT, and their consumption of RBCs accounted for nearly half of total units of transfused RBC during the study period; (II) the risk of receiving ≥10 units of RBCs during LT increased with lower BMI and preoperative Hct; and (III) MT was independently associated with more requirement of CRRT and mortality within 30 days.

Although there is a decrease in transfusion needs in LT due to preoperative anemia optimization, use of antifibrinolytics, close monitoring of hemostasis, intraoperative cell salvage, and better transfusion management, LT is still associated with intraoperative blood loss and MT (14). We used the traditional definition of MT and found that the incidence (10.4%) was lower than previous reports (3,15). This is largely due to different patient characteristics, diagnostic criteria, and follow-up periods. Since this group of patients, despite in a small percentage, consumes disproportionally higher amount of blood products, understanding risk factors may have an important role in resource utilization and management.

Decreased BMI and preoperative Hct were independently associated with an increased risk of MT during LT. The predictive model demonstrated relatively robust performance, achieving an AUC of 0.81. Previously, several studies have established the predictive value of BMI and preoperative hemoglobin levels for RBC transfusion in other operations, such as liver transplantation, cardiac surgery, and hip fracture surgery (2,16-18). However, there is a paucity of research addressing this issue in LT. Patients with end-stage pulmonary disease often experience malnutrition, characterized by low body weight, anemia, and hypoproteinemia (19). A reduced BMI may be associated with insufficient blood volume and decreased baseline fibrinogen level (20,21), thereby increasing intraoperative blood loss and the need for transfusions. In addition, different end-stage pulmonary diseases exhibit varying patterns of nutritional compromise and weight loss. Patients presenting with anemia typically exhibit more complex clinical conditions, often accompanied by underlying diseases. Previous research has demonstrated that preoperative anemia correlates with an increased risk of mortality post-LT (22); this study further confirms the significant influence of reduced preoperative Hct on the demand for substantial intraoperative transfusions. These findings suggest that improving preoperative nutritional status and correcting anemia could be vital strategies for reducing the incidence of MT.

The surgical time of MT patients is significantly prolonged, with a significant increase in intraoperative FFP and platelet infusion volume, accompanied by a decrease in urine output. This suggests that MT may be a sign of increased surgical complexity, and prolonged surgical time may further exacerbate blood loss and coagulation dysfunction. In addition, postoperative CRRT demand in MT patients significantly increased (53.3% vs. 13.8%), indicating that MT may have adverse effects on renal function through multiple mechanisms such as increased volume load, transfusion-related acute kidney injury, or hypoperfusion (23,24). Although there was no significant difference in postoperative hospital stay between the MT and the non-MT groups, the high CRRT demand of MT patients suggests that they require more complex postoperative management, which may indirectly increase the medical burden.

Some studies have evaluated the impact of blood transfusion on prognosis in LT, but the results are contradictory. In a review of a cohort of 311 bilateral LT recipients, Ong et al. did not observe any effect of RBC and FFP transfusion on 1-year all-cause mortality, while extensive use of platelets was associated with 1-year mortality (13). In a study of 729 double lung transplant recipients from nine transplant centers, Subramaniam et al. found that intraoperative transfusion of >4 units of RBCs was associated with an increased risk of grade 3 PGD within 72 hours (11). Among 147 single-center double lung transplant recipients, Atchade et al. analyzed that intraoperative transfusion of >5 units of RBCs was an independent risk factor for 90-day mortality and 1-year mortality (15). And Menger et al. found that lower postoperative hemoglobin levels in double lung transplant recipients were associated with increased mortality in the first year after surgery (25). In our study, MT was significantly associated with 30-day mortality (HR =5.13) after adjusting for other variables. The potential mechanisms included transfusion-related immune suppression, increased risk of infection, and inflammatory reactions caused by blood products (14). In addition, inflammatory processes triggered in the course of LT on ECMO are important factors that contribute to early outcome after transplantation (26).

Several limitations are worth mentioning. The retrospective design of our study has many inherent shortcomings. Although the data were collected prospectively, there is a possibility that confounding factors for MT or outcomes were not included in our study. In addition, patient demographics and management vary from center to center, which may affect the external validity of the results. Finally, the relatively small sample size, especially the number of patients in the MT group (n=15), may limit the statistical power of multivariate analysis. Future research should expand the sample size and include multi-center cohorts to validate the broad applicability of BMI and preoperative Hct as predictive factors for MT. In addition, further exploration should be conducted on the impact of MT on long-term prognosis, as well as the optimization of intraoperative transfusion management strategies, such as whether restrictive transfusion strategies can improve postoperative outcomes.

Conclusions

In conclusion, MT is not uncommon in LT and is closely associated with severe adverse outcomes after surgery, such as CRRT demand and high mortality rate. Low BMI and low preoperative Hct are important predictive factors for MT. Optimizing the patient’s nutritional status and correcting anemia before surgery may help reduce the need for intraoperative blood transfusion, ultimately aiming to decrease the incidence of MT and improve patient outcomes. Further multicenter research should be conducted in the future to explore more effective intraoperative blood transfusion management and intervention strategies, thereby improving the postoperative prognosis of lung transplant recipients.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-857/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-857/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-857/prf

Funding: This study was supported by the Zhejiang Provincial Health Innovation Talent Project (No. 2021RC066) and the Zhejiang Key Laboratory of Pain Perception and Neuromodulation.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-857/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional review board (IRB) of The Second Affiliated Hospital of Zhejiang University School of Medicine (No. 2022-0352), and no executed donor organs were used for these patients. The requirement for informed consent was waived by the IRB based on the retrospective nature of the study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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