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Special Considerations ABO-Incompatible Transplantation It is well recognized that infants have the best outcomes of all age groups; their median survival is now 20.7 years (see Fig 67.10) This survival advantage is probably due, at least in part, to the plasticity of the infant immune system, which has another advantage—the ability to safely undertake transplantation across blood groups.26 In an analysis of risk factors relative to the strategy of listing, failure to list for an ABO-incompatible graft and high clinical status emerged as the only factors associated with mortality.27 An ABO-incompatible transplant can not only be undertaken safely but also does not increase the risk of rejection or compromise posttransplant outcome and survival.28,29 Isohemagglutinins are not produced against the donor organ, so a further advantage is that, if retransplantation is required, an ABO-incompatible donor can be used again It is now increasingly clear from the renal and cardiac literature that successful ABO-incompatible transplants can be undertaken after infancy and even when significant isohemagglutinins are present To do so, however, does increase the risk of significant rejection If such a transplant is undertaken, strategies including plasmapheresis, immunoadsorption, and complement inhibition (eculizumab) should be available.30 Human Leukocyte Antigen Sensitization HLA (human leukocyte antigen) antibodies are not naturally occurring but acquired due to a sensitizing event.31 In the pediatric age group, this event is usually a medical intervention—especially blood products and homograft tissue used in congenital heart disease repair and increasingly the use of a VAD The prevalence of sensitization depends on the sensitivity of the testing methodology but is probably between 20% and 30% In the past the method of testing for these antibodies required mixing cells from a panel of blood donors with known HLA types and plasma from the patient undergoing transplant evaluation in the complement-dependent cytotoxicity test If the test was positive, the cells were destroyed Because the serum was tested against a panel of different HLA donors, the likelihood of the serum of the potential recipient having a significant quantity of HLA antibodies against a random donor can be calculated as a percentage using the PRA test; the higher the PRA, the more likely it would be that the recipient would receive a donor to whom he or she was sensitized The PHTS registry was evaluated for outcomes of sensitized versus nonsensitized recipients.32 It was found that by 1 year after listing, of those with a PRA of below 10%, 76% were transplanted and 9% deceased, versus 75% and 19% for those with a PRA greater than 50% For those who were transplanted, a PRA below 10% had a 1-year survival of 90% versus 73% with a PRA greater than 50% Thus, although waiting for a compatible donor increased the risk of dying on the list, accepting a donor to whom the recipient was sensitized led to a poorer posttransplant outcome To help decide which is the best approach—take the first organ offered or wait for the best match—a decision model analysis utilizing the Organ Procurement and Transplantation Network database was undertaken; it demonstrated that taking the first available organ offered provided the best outcomes overall.33 In the last decade solid-phase immunoassay has superseded the complementdependent cytotoxicity test for the detection and characterization of HLA antibodies.34 This is a much more sensitive technique but has resulted in a new paradigm with respect to the interpretation of donor-specific antibodies (DSAs) This test is able to detect HLA antibodies with exquisite sensitivity, but applying this knowledge clinically has proved difficult In vivo the HLA epitope that the HLA antibody is directed against may not be exposed; therefore although the antibody is present, it may not be able to attach to its target Controversy also surrounds the issue of whether it is important that HLA antibodies be complement-fixing—this is not usually tested for in standard solid-phase immunoassays.35 It is beyond the scope of this chapter to discuss the management of the sensitized patient in detail, but strategies include antibody removal by plasmapheresis or immunoadsorption, interruption of production by utilizing B-cell (e.g., rituximab) and plasma-cell inhibitors (e.g., bortezomib), and neutralization of their complement-fixing ability (e.g., eculizumab) Evidence of efficacy, however, is sparse, with only a few case reports or uncontrolled studies having appeared.36 Another consequence of our ability to detect HLA antibodies is the recognition that recipients may develop DSA to their graft after transplant Much still has to be learned about the significance of DSA posttransplant.37 These problems may be transient, in which case, especially if early in the posttransplant course, they may be of little significance If they are persistent, however, they are associated with worse graft survival.38 Although strategies to reduce posttransplant DSA are similar to those used before transplantation, their efficacy is as yet unknown.39 Mechanical Support as a Bridge to Transplantation The current state of mechanical circulatory support and available devices in pediatrics is covered elsewhere With regard to transplantation, the evolution of mechanical support options has provided multiple potential care paths including temporary versus durable support and a bridge to decision, recovery, or transplant, also allowing for crossover between these options The use of VAD as a bridge to transplant in the pediatric population has continued to increase significantly and currently about one-third of pediatric patients are transplanted from VAD support (Fig 67.15) It has allowed for reduced waitlist mortality7 without compromising posttransplant survival There are age-related differences, with more infants requiring ECMO support and resultant suboptimal outcomes9 (see Figs 67.13 and 67.16) Patients supported with a VAD can usually be mobile and undergo physical and nutritional rehabilitation while awaiting transplantation; this has likely contributed to the improved outcomes Serious morbidity—including stroke, bleeding, infection, and device malfunction— remain common.40 ... The use of VAD as a bridge to transplant in the pediatric population has continued to increase significantly and currently about one-third of pediatric patients are transplanted from VAD support (Fig... Mechanical Support as a Bridge to Transplantation The current state of mechanical circulatory support and available devices in pediatrics is covered elsewhere With regard to transplantation, the evolution of mechanical support options has provided multiple potential care paths including