title: Heparin-induced anaphylactic and anaphylactoid reactions: two distinct but overlapping syndromes.
abstract: BACKGROUND
  Heparin-induced anaphylactic and anaphylactoid reactions are of increasing clinical and scientific interest, particularly given the recent identification of a syndrome of heparin-induced anaphylaxis due to oversulfated chondroitin sulfate (OSCS), a contaminant in certain heparin preparations. However, heparin-induced anaphylactoid reactions also have been reported to be a consequence of immune-mediated heparin-induced thrombocytopenia (HIT).
  
  
  OBJECTIVE
  To summarize the clinical features and pathophysiology of two distinct disorders, HIT-associated anaphylactoid reactions as well as anaphylaxis resulting from OSCS-contaminated heparin.
  
  
  METHODS
  We review literature describing these two types of heparin-induced anaphylactic and anaphylactoid reactions, and seek potential pathophysiologic links between them.
  
  
  RESULTS
  Intravenous bolus heparin administered to patients with circulating 'HIT antibodies', usually as a result of recent heparin therapy, can produce anaphylactoid reactions, probably as a consequence of in vivo activation of platelets and, possibly, leukocytes. Affected patients often evince fever/chills, hypertension and/or acute respiratory compromise ('pseudo-pulmonary embolism'). In contrast, heparin-induced anaphylaxis is caused by activation of the contact system, with formation of vasoactive kinins (bradykinin, des-arg(9)-bradykinin). This latter syndrome has been linked in an epidemic form to administration of OSCS-contaminated heparin; these reactions feature prominent hypotension and laryngeal edema. Hemodialysis patients are at increased risk for both syndromes. There is evidence that OSCS-contaminated heparin itself increases the risk of HIT compared with non-contaminated heparin.
  
  
  CONCLUSIONS
  Two distinct syndromes of heparin-induced anaphylaxis and anaphylactoid reactions exist. These seem to share certain epidemiologic features, given that OSCS-contaminated heparin can produce anaphylaxis through contact system activation but also could increase risk of HIT and HIT-associated anaphylactoid reactions.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton Health Sciences, General Site, Hamilton, Ontario, Canada. twarken@mcmaster.ca
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Warkentin
authors.forename: Andreas
authors.initials: A
authors.lastname: Greinacher
mesh_terms: D000707:Anaphylaxis / Q000139:chemically induced / Q000209:etiology; D000925:Anticoagulants / Q000009:adverse effects* / Q000737:chemistry; D002809:Chondroitin Sulfates / Q000009:adverse effects*; D003167:Complement Activation; D004340:Drug Contamination; D006493:Heparin / Q000009:adverse effects* / Q000737:chemistry; D006801:Humans; D013921:Thrombocytopenia / Q000139:chemically induced / Q000150:complications
chemical_list: D000925:Anticoagulants; D006493:Heparin; D002809:Chondroitin Sulfates