title: Contemporary standards for the diagnosis and treatment of heparin-induced thrombocytopenia (HIT).
abstract: BACKGROUND
  Heparin binding to platelet factor 4 (PF4) generates a new antigenic epitope. In an unpredictable fashion, as many as approximately 17% of patients treated with unfractionated heparin (UFH) and approximately 8% treated with low-molecular-weight heparin (LMWH) subsequently develop the anti-heparin-PF4 antibodies that mediate heparin-induced thrombocytopenia and thrombosis (HIT). Very few of those patients with circulating anti-heparin-PF4 antibodies, however, progress to develop clinical HIT (referred to previously as Type II HIT). Only 20% of those who harbor antibodies ( approximately 3% of those exposed to heparin) will manifest the thrombocytopenia subsequently. Even fewer patients (0.03% to 0.09% of those exposed to heparin) experience the marked platelet activation and morbid thromboses characteristic of the HIT syndrome. The pathogenesis of heparin-induced thrombocytopenia (HIT) remains elusive. The pathophysiologic understanding to date has revolved around pathogenic anti-heparin-PF4 antibodies that trigger platelet activation, release of platelet procoagulant microparticles, and resultant thrombosis. The clinical diagnosis of HIT is confusing because current assays to detect anti-heparin-PF4 antibodies do not correlate well with the disease. Currently available assays lack either adequate sensitivity and interlaboratory reproducibility (ie, functional serotonin release assays) or specificity (ie, enzyme-linked immunosorbent assays or ELISAs).
  
  
  CONCLUSIONS
  Fortunately, the treatment for HIT is not confusing. The purposes of this review are as follows: (1) to examine the relevant clinical definition of HIT, (2) to explore our current understanding as to the pathogenesis of HIT, and (3) to present an algorithm for the identification and treatment of the HIT syndrome.
authors.affiliation: Division of Vascular Surgery, Department of Surgery, School of Medicine, University of California, San Francisco, Calif 94143, USA. baldwinz@surgery.ucsf.edu
authors.forename: Zachary K
authors.initials: ZK
authors.lastname: Baldwin
authors.forename: Austin L
authors.initials: AL
authors.lastname: Spitzer
authors.forename: Valerie L
authors.initials: VL
authors.lastname: Ng
authors.forename: Alden H
authors.initials: AH
authors.lastname: Harken
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects*; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D013921:Thrombocytopenia / Q000139:chemically induced / Q000175:diagnosis / Q000628:therapy
chemical_list: D000925:Anticoagulants; D006493:Heparin