192 E . A . Hayes et al .: J Extra Corpor Technol 2023 , 55 , 189 – 193
Figure 3 . Membrane-based plasmapheresis . A – Reduction in titers of anti-A and anti-B IgG and IgM . B – Reduction in HLA antibodies by average mean fluorescence intensity ( MFI ) at the DQ locus .
corresponding to a 1.7 – 2.5-fold decrease at the end of the twohour run .
Discussion
The presence of antibodies against HLA and ABO antigens and the historic association with rejection remains a barrier to successful transplantation for many patients [ 8 ]. There are various treatment strategies for antibody removal available to mitigate these risks at the time of transplant , including plasma exchange transfusion , plasmapheresis , and immunoabsorption . There is variable use of these strategies among transplant centers with no clear evidence that one strategy is associated with improved outcomes post-transplant .
Plasma exchange transfusion performed in the operating room prior to transplant remains the simplest and most costeffective method to remove circulating antibodies . Prior to initiation of cardiopulmonary bypass , approximately 1.5 – 3 times the patient ’ s total plasma volume is exchanged for type AB donor plasma [ 9 , 10 ]. However , there are several disadvantages to this strategy . Plasma exchange is not selective and therefore removes protective antibodies and clotting factors , increasing the risk of post-operative bleeding and infection . Additionally , the volume of blood products required limits use in larger patients and infers an increasing risk of transfusion-related mortality [ 11 ].
Alternatively , Robertson et al . recently published data utilizing immunoabsorption columns incorporated into the cardiopulmonary bypass circuit in ABO-I heart transplantation . With this method , a plasma separator and immunoadsorption column are incorporated into the EC circuit . After initiation of cardiopulmonary bypass , plasma is removed by the separator and filtered through the column with depleted plasma returned to the circulating volume of the EC circuit [ 12 ]. However , immunoabsorption columns are not readily available in many institutions in the United States . Furthermore , as this is a new technology , there is limited data on long-term outcomes .
Alternatively , plasmapheresis is commonly used in the peritransplant period . MP utilizes a filter with pores that are large enough to remove the plasma and the desired macromolecules , whereas CP relies on the rotational forces of centrifugation to separate blood components based on their density [ 13 ]. Plasmapheresis circuits can also be incorporated into the EC circuit to remove a portion of the patient plasma that is then replaced with albumin or donor-fresh frozen plasma . We found that both membrane-based and centrifuge-based plasmapheresis incorporated into the EC circuit quickly and effectively reduced circulating IT and HLA antibodies . Both membrane-based and centrifuge-based plasmapheresis reduced anti-A and anti-B titers with similar efficacy with a reduction of 93.7 % vs . 93.8 %, respectively . Centrifuge-based plasmapheresis may have some greater efficiency in the removal of HLA antibodies with a 2.0 – 3.5-fold decrease compared to a 1.7 – 2.5-fold decrease for membrane-based plasmapheresis . Both membrane and centrifuge-based plasmapheresis utilized at the time of transplantation have the potential to expand the donor pool for older or highly sensitized children , though further study is needed to verify similar results in vivo .
Conclusion
In this in vitro plasmapheresis model of IT and anti-HLA antibody reduction , both membrane-based and centrifuge-based plasmapheresis incorporated into the EC circuit can be used quickly and effectively to reduce circulating isohemagglutinin