LAUSR

A 4 mo male with complex congenital heart disease underwent ABOi transplantation (tx) (patient O+, donor AB+). Patient received multiple transfusions, but DSA were absent (PRA 0% pre-tx). Flow XM were negative. Patient underwent intra-operative plasma exchange for ABOi, and post-tx titers never exceeded 1:32. Chronic lung disease with poly-viral bronchiolitis worsened by tracheobronchomalacia complicated the clinical course, but cardiac function remained good. 6 m post-tx biopsy showed no evidence of acute cellular rejection (ACR) and/or vasculitis, but diffuse C4d staining was noted. Multiple C1q+ DSA developed (Table). Patient received IVIg and rituximab for possible AMR. Biopsy one month later showed only focal C4d presence, but still without signs of vascular injury or ACR. Patient continued with good graft function, though, respiratory problems persisted. He presented in the winter (13 m post-tx) with difficulty breathing and possible aspiration, with subsequent respiratory arrest leading to cardiac arrest, and failed resuscitation efforts. At autopsy, the tx heart showed no signs of AMR or vasculitis, but ACR (ISHLT Grade 3R) and severe allograft vasculopathy were present. Observations: 1) Multiple pre-tx transfusions prime patients to develop DSA and possible risks for post-tx acute AMR, 2) possible acute AMR appears to have been successfully treated, 3) but, ACR and vasculopathy developed despite the treatment and adequate prophylaxis, and 4) cardiac compromise through ACR and vasculopathy likely contributed to the patient’s demise. Additionally, we wonder whether the combination of patient anti-A and -B antibodies may have further adversely contributed to the cardiac compromise, despite previous reports. Conclusions: Patients with multiple pre-tx transfusions may be at higher risk for acute AMR and early development of vasculopathy, especially in the ABOi setting. Treatment for AMR may not be effective to prevent ACR and vasculopathy. Antibodies detected by C1q may have worse pathologic consequences.