Heparin-Induced Thrombocytopenia: A Focus on Thrombosis

Arterioscler Thromb Vasc Biol. 2021 Jan;41(1):141-152. doi: 10.1161/ATVBAHA.120.315445. Epub 2020 Dec 3.


Heparin-induced thrombocytopenia is an immune-mediated disorder caused by antibodies that recognize complexes of platelet factor 4 and heparin. Thrombosis is a central and unpredictable feature of this syndrome. Despite optimal management, disease morbidity and mortality from thrombosis remain high. The hypercoagulable state in heparin-induced thrombocytopenia is biologically distinct from other thrombophilic disorders in that clinical complications are directly attributable to circulating ultra-large immune complexes. In some individuals, ultra-large immune complexes elicit unchecked cellular procoagulant responses that culminate in thrombosis. To date, the clinical and biologic risk factors associated with thrombotic risk in heparin-induced thrombocytopenia remain elusive. This review will summarize our current understanding of thrombosis in heparin-induced thrombocytopenia with attention to its clinical features, cellular mechanisms, and its management.

Keywords: antibodies; heparin; platelets; thrombocytopenia; thrombosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antibodies / blood*
  • Anticoagulants / administration & dosage*
  • Anticoagulants / immunology
  • Antithrombins / therapeutic use
  • Blood Coagulation* / drug effects
  • Factor Xa Inhibitors / therapeutic use
  • Heparin / adverse effects*
  • Heparin / immunology
  • Humans
  • Platelet Factor 4 / immunology*
  • Risk Factors
  • Thrombocytopenia / blood
  • Thrombocytopenia / chemically induced*
  • Thrombocytopenia / drug therapy
  • Thrombocytopenia / immunology
  • Thrombosis / blood
  • Thrombosis / chemically induced*
  • Thrombosis / drug therapy
  • Thrombosis / immunology


  • Antibodies
  • Anticoagulants
  • Antithrombins
  • Factor Xa Inhibitors
  • PF4 protein, human
  • Platelet Factor 4
  • Heparin