title: Anti-platelet factor 4/heparin antibodies in patients with impaired graft function after liver transplantation.
abstract: 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 (PF4). Antibodies that are formed against the resulting PF4/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.
  
  
  OBJECTIVE
  To investigate the immune response against PF4/heparin complexes in patients undergoing LT.
  
  
  METHODS
  In this prospective cohort study, 38 consecutive patients undergoing LT were systematically screened for anti-PF4/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-PF4/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-PF4/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-PF4/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 PF4/heparin complexes in humans.
authors.affiliation: Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Bakchoul
authors.forename: V
authors.initials: V
authors.lastname: Assfalg
authors.forename: H
authors.initials: H
authors.lastname: Zöllner
authors.forename: M
authors.initials: M
authors.lastname: Evert
authors.forename: A
authors.initials: A
authors.lastname: Novotny
authors.forename: E
authors.initials: E
authors.lastname: Matevossian
authors.forename: H
authors.initials: H
authors.lastname: Friess
authors.forename: D
authors.initials: D
authors.lastname: Hartmann
authors.forename: G
authors.initials: G
authors.lastname: Hron
authors.forename: K
authors.initials: K
authors.lastname: Althaus
authors.forename: A
authors.initials: A
authors.lastname: Greinacher
authors.forename: N
authors.initials: N
authors.lastname: Hüser
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects* / Q000276:immunology; D001706:Biopsy; D005260:Female; D006083:Graft Occlusion, Vascular / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D010978:Platelet Factor 4 / Q000276:immunology*; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology; D013927:Thrombosis / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D010978:Platelet Factor 4; D006493:Heparin
keywords: antibody response; liver transplantation; platelet factor 4; platelets; vascular graft occlusion