title: Advances in the pathophysiology and treatment of heparin-induced thrombocytopenia.
abstract: OBJECTIVE
  To review the recent developments in understanding the pathophysiology of heparin-induced thrombocytopenia (HIT) and in applying this knowledge to the treatment of patients with suspected and proven HIT.
  
  
  RESULTS
  HIT pathophysiology is dynamic and complex. HIT pathophysiology is initiated by four essential components--heparin (Hep), platelet factor 4 (PF4), IgG antibodies against the Hep-PF4 complex, and platelet FcγRIIa. HIT is propagated by activated platelets, monocytes, endothelial cells, and coagulation proteins. Insights into the unique HIT antibody response continue to emerge, but without consensus as to the relative roles of B cells, T cells, and antigen-presenting cells. Platelet activation via FcγRIIa, the sine qua non of HIT, has become much better appreciated. Therapy remains challenging for several reasons. Suspected HIT is more frequent than proven HIT, because of the widespread use of Hep and the inadequacies of current diagnostic tests and scoring systems. In proven HIT, approved treatments reduce but do not eliminate thrombosis, and have substantial bleeding risk. Rational novel therapeutic strategies, directed at the initiating steps in HIT pathophysiology and with potential combinations staged over time, are in various phases of development.
  
  
  CONCLUSIONS
  Progress continues in understanding the breadth of molecular and cellular players in HIT. Translation to improved diagnosis and treatment is needed.
authors.affiliation: aDepartment of Medicine, Cardeza Foundation for Hematological Research, Thomas Jefferson University bDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: McKenzie
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Sachais
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects*; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D015539:Platelet Activation; D010978:Platelet Factor 4 / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D013921:Thrombocytopenia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*
chemical_list: D000925:Anticoagulants; D010978:Platelet Factor 4; D006493:Heparin; D013917:Thrombin