Temporal aspects of heparin-induced thrombocytopenia

N Engl J Med. 2001 Apr 26;344(17):1286-92. doi: 10.1056/NEJM200104263441704.


Background: Heparin-induced thrombocytopenia is a relatively common antibody-mediated drug reaction. We studied the temporal relation between previous or current heparin therapy and the onset of heparin-induced thrombocytopenia.

Methods: We examined the time between the start of heparin therapy and the onset of thrombocytopenia in 243 patients with serologically confirmed heparin-induced thrombocytopenia. We also investigated the persistence of circulating heparin-dependent antibodies by performing a platelet serotonin-release assay and an assay for antibodies against platelet factor 4. The outcome in seven patients who had previously had an episode of heparin-induced thrombocytopenia and were later treated again with heparin was also examined.

Results: A fall in the platelet count beginning four or more days after the start of heparin therapy occurred in 170 of the 243 patients (70 percent); in these patients, a history of previous heparin treatment did not influence the timing of the onset of thrombocytopenia. In the remaining 73 patients (30 percent), the onset of thrombocytopenia was rapid (median time of onset, 10.5 hours after the start of heparin administration); all these patients had been treated with heparin within the previous 100 days. During recovery from thrombocytopenia, heparin-dependent antibodies in the serum fell to undetectable levels at a median of 50 to 85 days, depending on the assay performed. In the seven patients who were given heparin again after the disappearance of heparin-dependent antibodies, a new episode of heparin-induced thrombocytopenia did not occur.

Conclusions: Heparin-induced thrombocytopenia can begin rapidly in patients who have received heparin within the previous 100 days. Heparin-dependent antibodies do not invariably reappear with subsequent heparin use.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies / blood
  • Anticoagulants / adverse effects*
  • Anticoagulants / immunology
  • Female
  • Heparin / adverse effects*
  • Heparin / immunology
  • Humans
  • Male
  • Middle Aged
  • Platelet Count
  • Retrospective Studies
  • Thrombocytopenia / blood
  • Thrombocytopenia / chemically induced*
  • Thrombocytopenia / immunology
  • Time Factors


  • Antibodies
  • Anticoagulants
  • Heparin