Hyperacute graft dysfunction in an orthotopic heart transplant in the presence of non-HLA antibodies

Abstract

Antibody‐mediated rejection (AMR) in heart transplants in the absence of anti‐HLA donor‐specific antibody (DSA) is not well studied or documented. This case reviews hyperacute fulminant graft dysfunction suspected to be mediated by non‐HLA antibodies. After cross clamp removal, the patient developed severe pulmonary edema, profound coagulopathy, and biventricular failure. The patient's presumed AMR, cardiogenic shock, and coagulopathy were treated with extracorporeal membrane oxygenation (ECMO), plasmapheresis, intravenous immunoglobulin (IVIG), multiple blood products, and prothrombin complex concentrate. The recipient was 0% panel‐reactive antibody (PRA), ABO, and crossmatch compatible. Intraoperative biopsy sample revealed a thrombotic process suggestive of a coagulation pathway activated by AMR; however, no C4d deposition was detected. Postmortem biopsies also suggested AMR. Retrospective testing of the patient's pretransplant serum revealed strong antiangiotensin II type 1 receptor (AT1R) antibodies and a strongly positive endothelial cell crossmatch. Anti‐AT1R antibodies are known to be AT1 receptor agonists and may trigger inflammation and activate the extrinsic coagulation pathway. Given the potential effects of signaling through the AT1R, the patient's preexisting anti‐AT1R antibodies and procoagulant therapy may have adversely affected the patient's clinical course.

Angiotensin II Type 1 Receptor Antibody-mediated Rejection Following Orthotopic Heart Transplant: A Single-center Experience

“…12 (3) Given the potential synergy between AT1R-Ab and DSA HLA-AMR, knowing AT1R-Ab status at transplant may aid in risk stratification. 12 (4) In the absence of clinical barriers (hypotension, hyperkalemia, or renal failure), ARB therapy may be considered in the setting of any measurable titer of DSA or AT1R-Ab.…”

“…[15][16][17][18] However, there are limited data regarding the contribution of AT1R-Abs following OHT; as such, the role of these antibodies to cardiac allograft survival remains controversial. 7,12,14,15,19,20 Further, it is likely that non-HLA antibodies both arise from and contribute to allograft injury. Thus, the understanding of the cause and effect relationship is challenging.…”

A Comprehensive Overview of the Clinical Relevance and Treatment Options for Antibody-mediated Rejection Associated With Non-HLA Antibodies

“…Despite a decrease in antibody levels after treatment with PP, IVIG, and ATG, AMR could not be controlled, and the patient developed thrombosis, eventually leading to death. 112 To the best of our knowledge, no clinical studies have evaluated the efficacy of treatment protocols on anti-PECR or antimyosin clearance. Specific therapies such as AT1R blockers or IdeS seem promising, but their long-term effects need to be investigated before these therapies can be safely implemented.…”

The emerging field of non–human leukocyte antigen antibodies in transplant medicine and beyond

“…[73][74][75] Interestingly, as in kidney, cases of hyperacute ABMR, with a thrombotic process suggestive of activation of the coagulation pathway, have been described. 76 Mechanical circulatory support devices (e.g., left ventricular assist devices), used in patients with advanced heart failure, are associated with high production of anti-AT1R antibodies, presumably related to exposure of endothelial antigen targets by severe endothelial disruption, thus rendering them vulnerable to the effect of these antibodies after transplantation. 77 In addition to clinical investigations in kidney and heart transplantation, the number of smaller studies in lung, 78 liver, [79][80][81][82][83] multivisceral and small bowel transplantation, 84 as well as in composite tissue transplantation 85 has grown exponentially and further supported the universality of the histologic patterns of rejection associated with anti-AT1R antibodies and their association with poor clinical outcomes.…”