title: A spontaneous prothrombotic disorder resembling heparin-induced thrombocytopenia.
abstract: BACKGROUND
  Antibodies against the "self" protein, platelet factor 4 (PF4), bound to heparin-the cause of immune heparin-induced thrombocytopenia-are believed invariably to be triggered by preceding heparin therapy. We describe a novel syndrome, spontaneous heparin-induced thrombocytopenia, in which clinical and serologic features characteristic of this adverse drug reaction develop in patients despite the absence of preceding heparin therapy.
  
  
  METHODS
  Three patients met the study criteria (clinical and serologic features of heparin-induced thrombocytopenia without preceding heparin exposure), of whom 2 patients were identified among 225 patients (0.89%, 95% confidence interval, 0.11%-3.17%) with serologically confirmed heparin-induced thrombocytopenia recognized during an 18-year period at 1 hospital. The platelet serotonin-release assay was used to detect heparin-dependent immunoglobulin G-induced platelet activation, and 2 enzyme immunoassays were used to detect antibodies against PF4/heparin.
  
  
  RESULTS
  Two patients presented with thrombocytopenia and multiple arterial thrombosis, and 1 patient presented with anaphylactoid reactions after 2 subcutaneous injections of low-molecular-weight heparin. All 3 patients had high levels of platelet-activating anti-PF4/heparin antibodies of immunoglobulin G class at presentation despite the absence of previous heparin exposure. However, each patient did have a preceding infectious or inflammatory event; 1 patient had concomitant antiphospholipid antibodies.
  
  
  CONCLUSIONS
  Circumstances other than heparin use can trigger a spontaneous disorder that closely mimics heparin-induced thrombocytopenia, further supporting the autoimmune nature of this adverse drug reaction.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. twarken@mcmaster.ca
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Warkentin
authors.forename: Michael
authors.initials: M
authors.lastname: Makris
authors.forename: Richard M
authors.initials: RM
authors.lastname: Jay
authors.forename: John G
authors.initials: JG
authors.lastname: Kelton
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood*; D005260:Female; D006801:Humans; D007118:Immunoassay; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D010978:Platelet Factor 4 / Q000276:immunology*; D013921:Thrombocytopenia / Q000276:immunology*; D013927:Thrombosis / Q000276:immunology
chemical_list: D000906:Antibodies; D007074:Immunoglobulin G; D010978:Platelet Factor 4