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

[heparin-induced thrombocytopenia]

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 .To investigate the immune response against PF 4 /heparin complexes in patients undergoing LT .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 .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 .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 .