80 M. J. Martinez et al.: J Extra Corpor Technol 2026, 58, 79--84
6 months after transplantation, the HLA-B effect arises in the first 2 years, and HLA-A mismatches have a detrimental effect on long-term graft survival [ 2 ].
HLA molecules constitute one of the two major immunological barriers( the other being ABO antigens) to be analyzed prior to a solid organ transplant. The presence of these antibodies in the recipient’ s serum is responsible for hyperacute rejections [ 1 ].
Regarding congenital heart disease and HLA antibodies, an elevated PRA has been reported to occur in 12 % to 19 % pediatric patients transplanted for end-stage congenital heart disease. The proportion of children transplanted with congenital heart disease is highest in the infant population( 63 %) but remains substantial in the adolescent age group( 24 %). These patients have often undergone multiple prior congenital heart surgeries and received blood transfusions, predisposing them to antibody formation. Shaddy et al. [ 3 ] and Hawkins et al. [ 4 ] characterized the formation of HLA class I and class II antibodies after implantation of cryopreserved allograft material for the repair or palliation of congenital heart disease. Within 3 months of implantation, the mean class I and II antibody levels reached 92 ± 15 % and 70 ± 26 %, respectively, and the high levels of circulating antibodies persisted for at least 12 months. The presence of allosensitizing material likely contributes to the higher incidence of HLA antibodies detected in children with congenital heart disease [ 5 ].
Current strategies to decrease allosensitization focus on the direct removal of circulating antibodies with plasmapheresis, inactivation of antibodies with IVIG, and B-lymphocyte depletion with rituximab. These approaches have also been used to treat antibody-mediated rejection after transplantation with encouraging results [ 6 ].
Plasma of the patient is separated from other components of blood, either by membrane filtration( mTPE) or centrifugation( cTPE). The plasma is removed with subsequent substitution of a replacement solution( e. g., human albumin and / or plasma) or a combination of crystalloid / colloid solution. In the literature, plasmapheresis is often used synonymously with TPE. The term high-volume TPE( TPE-HV) is used if > 2 plasma volumes are exchanged in a single session [ 7 ].
The plasma exchange procedure is performed using a continuous-flow cell separator, which is connected to the patient via two lines( extraction and return) through a dual-lumen central venous access. In particular situations, the connection may be made to another extracorporeal circulation device that is connected to the patient( such as a hemofilter, cardiopulmonary bypass machine, etc.). Blood is extracted from the patient through one line while the cellular components are mixed with the replacement fluid and returned to the patient through the other line( Figure 1).
The amount of plasma to be exchanged is calculated based on the patient’ s plasma volume, which is the difference between the total blood volume and the red cell mass. Once the total blood volume is obtained, and knowing the hematocrit value, the red cell mass can be calculated using the following formula:
Vol Hematocrit = 100 ¼ Plasma volume:
The replacement fluid to be used depends on the patient’ s condition. It is usually 5 % human albumin. In cases of coagulopathy or prior to surgery, a combination of albumin and fresh frozen plasma is used.
Sodium citrate, the most commonly used anticoagulant in therapeutic apheresis, works by chelating ionized calcium and preventing clot formation. Current automated apheresis machines control the citrate infusion rate to achieve anticoagulation while minimizing the risk of hypocalcemia. Therapeuticplasmaexchange( TPE) maybeindicatedfor:
Patients with heparin-induced thrombocytopenia( HIT) with or without thrombosis( HITT).
Patientswithantiphospholipidsíndrome.
Hypersensitized patients undergoing heart transplantation [ 8 ].
Antibody-mediated rejection( AMR) after heart transplantation occurs in approximately 7--18 % of recipients and is associated with acute cardiac graft dysfunction and increased risk of allograft failure. The major barrier to transplantation is anti-HLA antibodies, which are associated with AMR and post-transplant morbidity and mortality.
Current strategies to reduce the prevalence of posttransplant AMR in sensitized patients target the reduction of circulating donor-specific anti-HLA. During the immediate postoperative period, pre-sensitized heart transplant recipients may present with hemodynamic instability and hypoxemia because of AMR that requires extracorporeal membrane oxygenation( ECMO) support. Therefore, automated TPE in parallel with ECMO would be useful in this situation.
Susceptibility to infection from reduced immunoglobulin levels associated with TPE in AMR patients has not been clearly established. Jhang et al. [ 9 ] found that TPE in parallel with ECMO is technically possible, safe, and effective in reducing anti-HLA antibodies for the treatment of AMR of the transplanted heart. Another example of antibody clearance for possible rejection was demonstrated by Dellgren et al. [ 10 ] They showed that ABO-incompatible transplantation can be performed without significantly increased mortality or morbidity. There is an option of pre-emptive removal of anti-A and anti- B antibodies during plasma exchange on bypass before graft reperfusion and / or the low pre-transplantation antibody titers typical of recipients in the first year of life. Patients receiving ABO incompatible grafts showed a tendency to produce lower levels of antibodies directed against the incompatible blood group antigen than against the non-expressed antigen. In this group of patients, little or no evidence of vascular rejection was seen, and persistent cellular rejection did not occur during follow-up in recipients of ABO-incompatible grafts. An anecdotal example was reported by Adachi et al., who successfully conducted TPE via VAD circuitry in two pediatric patients who experienced humoral rejection following heart transplantation.
Additional studies are needed to determine the optimal timing, number, and frequency of TPE procedures, and to better establish a direct correlation between reduction in anti-HLA antibody titers and ventricular function and long-term outcome. However, given the high mortality associated with post-transplant AMR, especially in pediatric heart transplant recipients, early recognition and rapid treatment of acute post-transplant cardiac dysfunction should strongly be considered [ 11 ].