Risk factors for HAR in cardiac transplantation include high PRA, positive pre- or post-transplant crossmatch, induction therapy with OKT3, malignancy, and preceding infection . Additionally, there is emerging evidence that VAD implantation can contribute to HLA sensitization by inducing secondary T-cell activation and B-cell reactivity, thereby increasing the risk for antibody-mediated rejection . However, even VAD-bridged patients who are preoperatively identified as being highly sensitized may be candidates for cardiac transplantation. Lick et al. recently demonstrated that cardiac transplantation of LVAD patients with high PRA without preoperative crossmatch using on-bypass plasmapheresis and alemtuzumab resulted in equivalent midterm survival compared with non-sensitized patients .
PRA screening practices, crossmatch determinations, and management of sensitized patients vary considerably among institutions. Moreover, all PRA screening modalities are not created equal. Traditional techniques that are more commonly used at most institutions include cell-based complement-dependent cytotoxicity (CDC) and anti-human globulin-augmented lymphocytotoxicity assays . However, newer modalities such as enzyme-linked immunosorbent (ELISA) and flow cytometric (FCM) assays appear to be more sensitive in their ability to detect class II antigens than the older techniques. Furthermore, FCM-detectable pre-transplant antibodies better differentiated sensitized versus non-sensitized patients, and predicted allograft rejection more reliably than the CDC method . Our institution employs Luminex single antigen bead assays for HLA antibody screening.
Once antibody-mediated rejection has been identified, options for treatment include plasmapheresis, immunoadsorption, IVIG, cyclophosphamide administration, increasing doses of immunosuppression, and rituximab [2, 4]. Rituximab is a chimeric humanized monoclonal antibody against the pan-B cell surface molecule CD20 that has showed promise in treating antibody-mediated rejection in cardiac transplantation as well as inadvertent ABO-incompatible lung transplantation . Although rituximab induces a rapid depletion of CD20-expressing B cells in peripheral blood, it has little or no effect on circulating antibodies. Therefore, several reports have advocated for complementing the use of rituximab with modalities that deplete circulating antibodies such as plasmapheresis, IVIG, or immunoadsorption. Other treatment options reported in the literature include cyclophosphamide, OKT3, and anti-thymocyte globulin . In our patient, the use of IVIG and plasmapheresis as an adjunct to rituximab resulted in an excellent outcome.
In addition to the use of appropriate immunotherapy targeting antibody-mediated rejection, the employment of biventricular CentriMag VAD support was critical in achieving complete functional recovery in this case. The cannulation strategy employed here allowed optimal decompression of both left and right sides of the heart during recovery. In particular, cannulating the left side of the heart through both the LV apex and the right superior pulmonary vein ensured complete decompression of the left ventricle. Excellent flows were achieved allowing ongoing support of organ function. Since heparin was not used in the early post-operative period, early bleeding complications were avoided. Since the sternum was able to be closed, infection and sternal wound complications were also avoided in this heavily immunosuppressed patient. Avoidance of early bleeding, preventing complications of an open sternum, and successful ongoing support of allograft function while the heart was being rescued allowed for a successful outcome.