J Extra Corpor Technol 2023 , 55 , 189 – 193 Ó The Author ( s ), published by EDP Sciences , 2023 https :// doi . org / 10.1051 / ject / 2023034
Available online at : ject . edpsciences . org
TECHNIQUE or APPLICATION
An in vitro comparison of intra-operative isohemagglutinin and human leukocyte antigen removal techniques in pediatric heart transplantation
Emily A . Hayes ( MD ) 1 ,* , Ashley B Walczak ( MBA , CCP , FPP ) 1 , Erin Goodhue Meyer ( DO , MPH ) 2 , Kathleen Nicol ( MD ) 3 , Matthew Deitemyer ( RN , BSN ) 1 , Vicky Duffy ( RRT ) 1 , Michelle Moore Padilla ( MD ) 4 , Robert J . Gajarski ( MD , MHSA ) 1 , and Deipanjan Nandi ( MD , MSc ) 1
1 The Heart Center , Nationwide Children ’ s Hospital , Columbus , OH 43205 , USA 2 Department of Hematology / Apheresis , Nationwide Children ’ s Hospital , Columbus , OH 43205 , USA 3 Department of Pathology , Nationwide Children ’ s Hospital , Columbus , OH 43205 , USA 4 Division of Cardiology , Department of Pediatrics , Emory University School of Medicine , Atlanta , GA 30322 , USA Received 23 January 2023 , Accepted 21 August 2023
Abstract – Background : Highly sensitized pediatric patients awaiting heart transplantation experience longer wait times and thus higher waitlist mortality . Similarly , children less than 2 years of age have increased waitlist times and mortality when compared to their older peers . To improve the likelihood of successful transplantation in these patients , various strategies have been utilized , including peri-operative plasmapheresis . However , limited data exists comparing plasmapheresis techniques for antibody reduction . This study ’ s aim was to compare the in vitro magnitude of isohemagglutinin titers ( IT ) and human leukocyte antigen ( HLA ) antibody removal and the time required between membrane-based plasmapheresis ( MP ) and centrifuge-based plasmapheresis ( CP ) incorporated into the extracorporeal ( EC ) circuit . Methods : Two MP ( Prismaflex ) and two CP ( Spectra Optia , Terumo BCT ) circuits were incorporated into four separate EC circuits primed with high titer , highly sensitized type O donor whole blood . Assays were performed to determine baseline IT and anti-HLA antibodies and then at 30-minute increments until completion of the run ( two plasma volume exchanges ) at two hours . Results : There was a decrease in anti-A and anti-B IgM and IgG titers with both MP and CP . Mean anti-A and anti-B titer reduction was by 4.625 titers ( 93.7 % change ) and 4.375 titers ( 93.8 % change ) using MP and CP , respectively . At 2 h of apheresis , CP reduced 62.5 % of all ITs to 1:4 , while MP reduced 50 % of ITs to 1:4 . Additionally , reduction of anti-HLA class II antibody to mean fluorescence intensity ( MFI ) < 3000 was achieved with both MP and CP . At 2 h of apheresis , CP reduced MFI by 2 – 3.5 fold and MP reduced MFI by 1.7 – 2.5 fold . Both demonstrated similar hemolytic and thrombotic profiles . Conclusions : In this in vitro plasmapheresis model of IT and anti-HLA antibody reduction , both MP and CP incorporated into the EC circuit can be used quickly and effectively to reduce circulating antibodies . While CP may have some greater efficiency , further study is necessary to verify this in vivo .
Key words : Isohemagglutinin , Human Leukocyte Antigen , Plasmapheresis , Pediatric Heart Transplantation .
Introduction
Heart transplantation remains the most effective treatment for patients with advanced heart failure refractory to medical management [ 1 ]. Over the past several decades , the outcomes following pediatric heart transplantation have continued to improve with a 1-year survival of over 90 % [ 2 ]. However , the waitlist mortality in the United States remains high at 17 %, ultimately limiting the use of this treatment in the pediatric patient population [ 3 ]. Furthermore , waitlist times are prolonged for smaller and highly sensitized children , leading to increased mortality in these patients [ 4 ].
In an effort to decrease waitlist mortality , strategies for the transplantation of highly sensitized patients and expanded use of ABO-I transplantation have progressed . One such strategy is the use of peri-operative plasmapheresis , including membrane-based plasmapheresis ( MP ) and centrifuge-based plasmapheresis ( CP ) [ 5 ]. Despite the common use of these techniques for both isohemagglutinin and HLA antibody removal , limited data exists to compare their effectiveness . This study aimed to
* Corresponding author : emily . hayes @ nationwidechildrens . org
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