Transfusion-induced HLA antibodies are short-lived and rarely recur post-heart transplantation: a single-center retrospective study with implications for virtual crossmatching.

Introduction: The development of human leukocyte antigen (HLA) antibodies poses a major challenge in transplantation by limiting donor compatibility and increasing the risk of graft failure. In patients with advanced heart failure, ventricular assist devices (VADs) are frequently used as a bridge to transplantation and often necessitate perioperative blood transfusions, a recognized trigger for HLA sensitization. However, the risk factors, timing, and clinical relevance of transfusion-induced HLA antibodies in VAD recipients remain incompletely defined. Methods: We conducted a retrospective analysis of 60 adult heart transplant candidates who underwent VAD implantation and received blood transfusions. HLA antibody profiles were assessed at three time points: pre-VAD implantation, post-VAD/pre-transplantation, and post-transplantation. Patients were categorized according to the number of newly detected HLA antibodies following VAD implantation as non-producers (NP; no new antibodies), low producers (LP; 1-10 antibodies), or high producers (HP; >10 antibodies). Associations between antibody development and demographic characteristics, transfusion exposure, pre-existing sensitization, antibody persistence, and transplant outcomes were evaluated. Results: Following VAD implantation, 73% of patients developed new HLA antibodies, with 65% of these antibodies emerging during the post-VAD/pre-transplant interval. Patient distribution was 35.0% NP, 51.7% LP, and 13.3% HP. Age, ethnicity, and transplant rates were comparable across groups; however, females were disproportionately represented in the HP group (75%, 6 of 8). Neither the number nor the type of blood products transfused was associated with antibody development. The majority of transfusion-associated HLA antibodies were transient, declining rapidly and rarely recurring after transplantation. In contrast, persistent antibodies were predominantly pre-existing and were more frequently observed in female patients, consistent with prior sensitization events such as pregnancy. Notably, unsensitized male patients demonstrated minimal antibody formation following transfusion. Discussion: These findings indicate that transfusion-induced HLA antibodies in VAD recipients are generally transient and lack durable serologic significance, with little evidence of post-transplant rebound. In contrast, sustained alloimmune responses are primarily driven by pre-existing sensitization, particularly pregnancy-related exposure in female patients. These results support a more individualized approach to HLA antibody surveillance and virtual crossmatching, especially in patients with limited transfusion exposure and no prior sensitization.