Heparin-induced skin lesions and other unusual sequelae of the heparin-induced thrombocytopenia syndrome: a nested cohort study

Chest. 2005 May;127(5):1857-61. doi: 10.1378/chest.127.5.1857.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphylaxis / etiology
  • Anticoagulants / adverse effects*
  • Cohort Studies
  • Heparin / adverse effects*
  • Humans
  • Platelet Count
  • Skin Diseases / chemically induced*
  • Thrombocytopenia / chemically induced*
  • Thrombocytopenia / complications*


  • Anticoagulants
  • Heparin