Virtual Crossmatching: Principles, Practices, and the Path Forward - An ASHI/CAP Collaborative.

Abstract

Donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) are a significant barrier to solid organ transplant and can lead to poor outcomes in the posttransplant setting. The physical crossmatch (PXM), including the complement-dependent cytotoxicity crossmatch and the flow cytometry crossmatch, has substantially reduced the incidence of hyperacute rejection and, for years, has been the gold standard for compatibility assessment before transplant. However, the advent of solid-phase anti-HLA antibody testing and molecular HLA typing has allowed the introduction and rise of the virtual crossmatch (VXM). With a high negative predictive value, the VXM has proven to be more sensitive than the PXM in detecting DSA. Recent regulations by the Centers for Medicare & Medicaid Services now recognize the VXM as a suitable alternative to the PXM in the pretransplant compatibility assessment. As the VXM gains acceptance, it is imperative that we understand its complexities, such as its definition, application, advantages, and disadvantages. In this review, we examine the principles underlying the VXM, including both generally accepted concepts and areas under debate. Furthermore, we highlight current applications and discuss opportunities for future improvement.