Clinical significance of anti‐HLA antibodies associated with ventricular assist device use in pediatric patients: A United Network for Organ Sharing database analysis

Abstract

While VAD use in pediatric patients has previously been associated with anti-HLA antibody production, the clinical significance of these antibodies is unclear. We investigated the clinical impact of anti-HLA antibodies associated with VAD use in a large cohort of pediatric HTx recipients. From 2004 to 2011, pediatric cardiomyopathy patients post-HTx (N=1288) with pre-HTx PRA levels were identified from the United Network for Organ Sharing database. PRA levels were compared between VAD patients and those with no history of MCS. Incidence of rejection and overall survival were compared between VAD and non-MCS groups after stratification by PRA and age. VAD recipients were more likely to produce anti-HLA antibodies than non-MCS patients (25.5% vs 10.5% had PRA>10%, P<.0001). Sensitized VAD patients (PRA>10%) had a higher incidence of rejection within 15 months of HTx compared to sensitized non-MCS patients (57.1% vs 35.9%, P=.02). There was no intergroup difference in 15-month mortality. Among pediatric cardiomyopathy patients supported with a VAD, the presence of anti-HLA antibodies prior to HTx is associated with an increased risk of rejection. The mechanism of the association between VAD-associated antibodies and early rejection is unclear and warrants further investigation.

Modifications to therapeutic plasma exchange to achieve rapid exchange on cardiopulmonary bypass prior to pediatric cardiac transplant

“…This has been attributed to the inflammatory response to foreign mechanical elements, increased blood product exposure, and the risk of infection associated with VAD implantation. The same trend is now being observed in children as the pediatric VAD experience evolves 9‐11 …”

“…The same trend is now being observed in children as the pediatric VAD experience evolves. [9][10][11] One retrospective study demonstrated an increased incidence of acute rejection in allosensitized children with VAD support compared to sensitized peers who were not exposed to VADs. 11 High PRA, then, may not only occur with more frequency in the VAD population, but may be of more clinical significance to those children requiring mechanical circulatory support.…”

“…[9][10][11] One retrospective study demonstrated an increased incidence of acute rejection in allosensitized children with VAD support compared to sensitized peers who were not exposed to VADs. 11 High PRA, then, may not only occur with more frequency in the VAD population, but may be of more clinical significance to those children requiring mechanical circulatory support. In addition, children are more likely than adults to utilize a pulsatileflow VAD, which, when compared to continuous-flow VADs, portend a higher likelihood of allosensitization.…”

Three decades of collaboration through the Pediatric Heart Transplant Society Registry: A journey through registry data with a highlight on children with single ventricle anatomy

“…p < .01. This is particularly notable given the consistent definition and reporting of rejection events within the PHTS Registry across these eras.There are many factors that affect risk of rejection which may differ by pretransplant diagnosis, including the use of homograft material for vessel reconstruction or valve replacement, exposure to blood products, and age of the recipient 11,12. Thus, freedom from rejection was stratified by cardiomyopathy and CHD diagnosis.…”

Advancing the field of anti‐HLA sensitization management prior to pediatric heart transplantation

“…In the field of pediatric heart transplantation, things we know include the following: over the past decade, ventricular assist device (VAD) use as a bridge to transplant has become more and more common, with nearly 30% of pediatric transplants in 2013‐2014 bridged with VAD compared to only about 15% in 2007‐2008; VAD use in pediatrics is associated with higher rates of sensitization to HLA prior to transplant; pediatric heart transplant across a positive donor‐specific complement‐dependent cytotoxicity cross‐match (CDC‐XM) is related to increased post‐transplant rejection, graft dysfunction and failure, and risk for graft coronary vasculopathy; however, presensitization is also associated with high wait‐list mortality reflecting an historical requirement for a negative CDC‐XM . These points provide the background for the importance of the publication by Magdo et al . in which they seek to determine the clinical significance of HLA antibodies produced specifically in response to VAD prior to pediatric heart transplant.…”