Pediatric Biopsy Considerations

Diagnosis of AMR in the pediatric population

Published prevalence of AMR after pediatric heart transplantation is higher than that reported in the majority of adult centers and ranges from 10% to 59%, depending on whether cardiac dysfunction is required for AMR diagnosis. Like in the adult population, subclinical AMR frequently occurs in the pediatric population. The higher incidence is likely due to a combination of sensitization and medication non-compliance, particularly in adolescents.

The pathological diagnosis of AMR in the pediatric population is no different than adults, relying on the same combined histology and immunohistochemistry approach used in the adult population. The ISHLT WF for pathologic scoring of AMR severity is applicable to the pediatric population.

Biopsy Size & Cellularity

As already stated in the cellular rejection tutorial, endomyocardial biopsies performed in the pediatric population are characterized by smaller size and by an increased impression of cellularity. At low power, the latter should not be mistaken with a "busy B" pattern. At high power, careful assessment of the microcirculation is warranted to identify significant intravascular mononuclear cells. One should be aware that plump endothelial cells are frequently observed in the pediatric biopsies and should be interpreted with caution.

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Sensitization in the pediatric population

According to the ISHLT registry, the percentage of sensitized patients, as defined by panel-reactive antibodies (PRA) of >10%, increased from 20% in 2005 to 29% in 2010. Sensitizing events in these patients include transfusion of blood products (especially platelets), use of ventricular assist devices, infections, and previous surgery for congenital heart disease, especially with the use of human homograft tissue. In the Pediatric Heart Transplant Study database and the ISHLT registry, congenital heart disease were associated with both increased risk factor for death after transplantation and of developing PRA of >50%. Having a Norwood procedure, prior listing, and sternotomy before listing were also all significant risks. Elevated PRA in children listed for heart transplantation is associated with longer waiting times to transplantation and increased pre-transplant mortality. High PRA is also associated with a 2-fold increase in early post-transplant mortality.

ABO incompatible allografts

Infants less than 1 year of age lack antibodies against blood group antigens since humoral immunity to carbohydrate moieties is poorly developed at this age. This allows for transplantation across blood types. Although AMR has been reported in pediatric ABO incompatible heart transplantation, infants who received these transplants had equivalent one-year survival. Immune tolerance to the graft ABO type develops (accommodation), though there is the theoretic possibility of bound anti-ABO antibody on the graft endothelium initiating the complement cascade leading to C4d positivity but with normal histopathology and no graft dysfunction.

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