title: Antiplatelet factor 4/heparin antibodies in patients with gram negative bacteremia.
abstract: Heparin-induced thrombocytopenia (HIT) is an antibody-mediated syndrome of thrombocytopenia and prothrombotic state that follows exposure to heparin. However, spontaneous HIT has been described in the setting of infection, without evidence of previous heparin administration. Since PF4 binds to lipid A portion of lipopolysaccharide, we tested for the presence of antiPF4/heparin antibodies in patients with gram-negative bacteremia. Patients with bacteremia had higher titers of antiPF4/heparin antibodies compared to normal controls 26.3 ± SD 34 units, N=32 versus 6.3 ± SD 2.38 units, N=10, P=0.001. FITC-labeled PF4 interacted with lipopolysaccharide in a concentration-dependent manner as determined by quenching of the emission spectrum following excitation at λ 488. In addition, immunoaffinity purified antiPF4/Heparin antibodies from 3 patients with HIT cross-reacted with PF4/heparin complex. These results show that PF4/LPS complex is immunogenic and can elicit cross-reacting antibodies against PF4/Heparin, providing an explanation for the presence of these antibodies in individuals, who were never been exposed to heparin before. These antibodies may also be at least partly responsible for the thrombocytopenia associated with infection.
authors.affiliation: Michael E. DeBakey Veterans Affairs Medical Center, Department of Medicine, Baylor College of Medicine, Houston, TX United States.
authors.forename: Georgios
authors.initials: G
authors.lastname: Pongas
authors.forename: Swapan Kumar
authors.initials: SK
authors.lastname: Dasgupta
authors.forename: Perumal
authors.initials: P
authors.lastname: Thiagarajan
mesh_terms: D000906:Antibodies / Q000097:blood / Q000276:immunology*; D016470:Bacteremia / Q000097:blood / Q000276:immunology*; D016022:Case-Control Studies; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D016905:Gram-Negative Bacterial Infections / Q000276:immunology*; D006493:Heparin / Q000276:immunology*; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D010978:Platelet Factor 4 / Q000276:immunology*; D013921:Thrombocytopenia / Q000276:immunology*
chemical_list: D000906:Antibodies; D008070:Lipopolysaccharides; D010978:Platelet Factor 4; D006493:Heparin