Anti‐platelet factor 4/heparin antibodies in patients with impaired graft function after liver transplantation

Summary Background Heparin, the standard perioperative anticoagulant for the prevention of graft vessel thrombosis in patients undergoing liver transplantation ( LT ), binds to the chemokine platelet factor 4 ( PF 4). Antibodies that are formed against the resulting PF 4/heparin complexes can induce heparin‐induced thrombocytopenia. LT is a clinical situation that allows the study of T ‐cell dependency of immune responses because T ‐cell function is largely suppressed pharmacologically in these patients to prevent graft rejection. Objectives To investigate the immune response against PF 4/heparin complexes in patients undergoing LT . Patients and Methods In this prospective cohort study, 38 consecutive patients undergoing LT were systematically screened for anti‐ PF 4/heparin antibodies (enzyme immunoassay and heparin‐induced platelet aggregation assay), platelet count, liver function, and engraftment. Results At baseline, 5 (13%) of 38 patients tested positive for anti‐ PF 4/heparin IgG (non‐platelet‐activating) antibodies. By day 20, an additional 5 (15%) of 33 patients seroconverted for immunoglobulin G (two platelet‐activating) antibodies. No patient developed clinical heparin‐induced thrombocytopenia. Two of six patients with graft function failure had anti‐ PF 4/heparin IgG antibodies at the time of graft function failure. Graft liver biopsy samples from these patients showed thrombotic occlusions of the microcirculation. Conclusions Anti‐ PF 4/heparin IgG antibodies are generated despite strong pharmacologic suppression of T cells, indicating that T cells likely have a limited role in the immune response to PF 4/heparin complexes in humans.