title: Fondaparinux: does it cause HIT? Can it treat HIT?
abstract: Heparin-induced thrombocytopenia (HIT) is an antibody-mediated prothrombotic disorder triggered by PF4-binding polyanions, usually heparin. The pentasaccharide anticoagulant, fondaparinux, despite its negative charge and structural similarity to heparin, does not usually promote antibody binding to PF4 (owing to absent/weak 'cross-reactivity'). Thus, despite its ability to trigger anti-PF4/heparin antibodies ('immunogenicity'), fondaparinux has low - but not zero - risk of inducing HIT de novo, or of exacerbating HIT when antibodies are already present. Indeed, despite rare reports of fondaparinux-induced HIT, this 'dissociation' between immunogenicity and cross-reactivity suggests that fondaparinux should be effective in treating HIT, as supported by several observational studies. An emerging issue: will clinicians accept this favorable experience of fondaparinux for treating HIT when a lack of randomized trials will hinder regulatory approval for this indication?
authors.affiliation: Michael G DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada. twarken@mcmaster.ca
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Warkentin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology; D000925:Anticoagulants / Q000008:administration & dosage* / Q000627:therapeutic use*; D000936:Antigen-Antibody Complex / Q000187:drug effects; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D005260:Female; D000077425:Fondaparinux; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010978:Platelet Factor 4 / Q000276:immunology / Q000378:metabolism; D011134:Polysaccharides / Q000008:administration & dosage* / Q000627:therapeutic use*; D012306:Risk; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000906:Antibodies; D000925:Anticoagulants; D000936:Antigen-Antibody Complex; D011134:Polysaccharides; D010978:Platelet Factor 4; D006493:Heparin; D000077425:Fondaparinux