title: Management of heparin-induced thrombocytopenia.
abstract: BACKGROUND
  Heparin-induced thrombocytopenia (HIT) is a rare but severe prothrombotic adverse effect of heparin treatment. The underlying cause is the formation of highly immunogenic complexes between negatively charged heparin and positively charged platelet factor 4 (PF4). Resulting antibodies against these PF4/heparin complexes can activate platelets via the platelet FcγIIa receptor, leading to thrombin generation and thus to the paradox of a prothrombotic state despite thrombocytopenia and application of heparin. Prompt diagnosis of HIT is important in order to change treatment to prevent severe thromboembolic complications. However, this is often difficult as thrombocytopenia is frequent in hospitalized patients and the commercially available laboratory tests for HIT antibodies have a high negative predictive value but only a poor positive predictive value. This leads to overdiagnosis and overtreatment of HIT, which also bear the risk for adverse outcomes.
  
  
  METHODS
  This review aims at resuming recent data on HIT, thereby focusing on the role of new anticoagulants and providing a framework for diagnosis and treatment. Furthermore, it provides some insights into the pathogenesis of this peculiar adverse drug reaction and ventures a guess at its future relevance in clinical practice.
  
  
  CONCLUSIONS
  New drugs which are strongly negatively charged should be assessed for their capacity to form complexes with PF4. If they do so, they bear the risk of inducing a HIT-like immune response. The immunology of HIT is still largely unresolved. Understanding HIT might provide insights into other immune and autoimmune response mechanisms.
authors.affiliation: Institute for Immunology and Transfusion Medicine, University Medicine Ernst Moritz Arndt University Greifswald, Sauerbruchstrasse, 17487 Greifswald, Germany.
authors.forename: Miriam E
authors.initials: ME
authors.lastname: Jaax
authors.forename: Andreas
authors.initials: A
authors.lastname: Greinacher
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D013921:Thrombocytopenia / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D000925:Anticoagulants; D006493:Heparin