title: Heparin-induced skin lesions and other unusual sequelae of the heparin-induced thrombocytopenia syndrome: a nested cohort study.
abstract: BACKGROUND
  Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating, heparin-dependent IgG antibodies (HIT-IgG). Although HIT is known to predispose the patient to thrombosis, the relationship between the formation of HIT-IgG and various other unusual clinical sequelae putatively linked with the HIT syndrome, such as heparin-induced skin lesions and acute anaphylactoid reactions following treatment with an IV heparin bolus, is not clear.
  
  
  METHODS
  We used data from a clinical trial of postoperative heparin prophylaxis to compare the frequency of one or more predefined unusual clinical sequelae developing in 20 patients who formed platelet-activating HIT-IgG with 80 control patients who did not form HIT-IgG (nested cohort study).
  
  
  RESULTS
  Five of the 20 patients in whom HIT-IgG developed had one or more unusual clinical sequelae, compared with none of 80 control patients (25% vs 0%, respectively; odds ratio, infinity; 95% confidence interval, 4.3 to infinity; p < 0.001). The unusual complications included heparin-induced erythematous or necrotic skin lesions (n = 4), an anaphylactoid reaction following IV heparin bolus use (n = 1), and warfarin-associated venous limb ischemia (n = 1). Thrombocytopenia, as it is conventionally defined (ie, platelet count fall to < 150 x 10(9) cells/L) developed in only one of these five patients.
  
  
  CONCLUSIONS
  Certain unusual clinical sequelae, such as heparin-induced skin lesions, are strongly associated with the formation of HIT-IgG and should be considered as manifestations of the HIT syndrome, even in the absence of thrombocytopenia as conventionally defined.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada. twarken@mcmaster.ca <twarken@mcmaster.ca>
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Warkentin
authors.forename: Robin S
authors.initials: RS
authors.lastname: Roberts
authors.forename: Jack
authors.initials: J
authors.lastname: Hirsh
authors.forename: John G
authors.initials: JG
authors.lastname: Kelton
mesh_terms: D000707:Anaphylaxis / Q000209:etiology; D000925:Anticoagulants / Q000009:adverse effects*; D015331:Cohort Studies; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D010976:Platelet Count; D012871:Skin Diseases / Q000139:chemically induced*; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000150:complications*
chemical_list: D000925:Anticoagulants; D006493:Heparin