Delayed-onset heparin-induced thrombocytopenia and thrombosis

Ann Intern Med. 2001 Oct 2;135(7):502-6. doi: 10.7326/0003-4819-135-7-200110020-00009.


Background: Heparin-induced thrombocytopenia is a prothrombotic drug reaction caused by platelet-activating antibodies that recognize complexes of platelet factor 4 and heparin.

Objective: To describe a syndrome termed delayed-onset heparin-induced thrombocytopenia, in which thrombocytopenia and thrombotic events begin 5 or more days after withdrawal of heparin.

Design: Case series.

Setting: Secondary and tertiary care hospitals.

Patients: 12 patients who presented with serologically confirmed, delayed-onset heparin-induced thrombocytopenia, including 6 outpatients presenting after hospital discharge.

Measurements: The platelet serotonin-release assay was used to measure IgG-induced heparin-dependent and heparin-independent platelet activation; an enzyme immunoassay that detects IgG against platelet factor 4-heparin complexes was also used.

Results: Patients with delayed-onset heparin-induced thrombocytopenia presented with thrombocytopenia and associated thrombosis a mean of 9.2 days (range, 5 to 19 days) after stopping heparin therapy. Nine patients received additional heparin, with further decrease in platelet counts. Compared with controls, patients with delayed-onset heparin-induced thrombocytopenia had higher titers of IgG antibodies to platelet factor 4-heparin and greater IgG-induced heparin-dependent and heparin-independent platelet activation.

Conclusions: Delayed-onset heparin-induced thrombocytopenia should be suspected when patients present with thrombocytopenia and thrombosis up to 3 weeks after exposure to heparin. This syndrome could be caused by high titers of platelet-activating IgG induced by heparin.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticoagulants / adverse effects*
  • Anticoagulants / immunology
  • Female
  • Heparin / adverse effects*
  • Heparin / immunology
  • Humans
  • Immunoenzyme Techniques
  • Immunoglobulin G / blood
  • Male
  • Platelet Activation
  • Platelet Count
  • Platelet Factor 4 / immunology
  • Serotonin / blood
  • Syndrome
  • Thrombocytopenia / chemically induced*
  • Thrombosis / chemically induced*
  • Time Factors


  • Anticoagulants
  • Immunoglobulin G
  • Serotonin
  • Platelet Factor 4
  • Heparin