The complicated relationships of heparin-induced thrombocytopenia and platelet factor 4 antibodies with COVID-19

Int J Lab Hematol. 2021 Aug;43(4):547-558. doi: 10.1111/ijlh.13582. Epub 2021 May 17.


COVID-19 (coronavirus disease 2019) represents a prothrombotic disorder, and there have been several reports of platelet factor 4/heparin antibodies being present in COVID-19-infected patients. This has thus been identified in some publications as representing a high incidence of heparin-induced thrombocytopenia (HIT), whereas in others, findings have been tempered by general lack of functional reactivity using confirmation assays of serotonin release assay (SRA) or heparin-induced platelet aggregation (HIPA). Moreover, in at least two publications, data are provided suggesting that antibodies can arise in heparin naïve patients or that platelet activation may not be heparin-dependent. From this literature, we would conclude that platelet factor 4/heparin antibodies can be observed in COVID-19-infected patients, and they may occur at higher incidence than in historical non-COVID-19-infected cohorts. However, the situation is complex, since not all platelet factor 4/heparin antibodies may lead to platelet activation, and not all identified antibodies are heparin-dependent, such that they do not necessarily reflect "true" HIT. Most recently, a "HIT-like" syndrome has reported in patients who have been vaccinated against COVID-19. Accordingly, much more is yet to be learnt about the insidious disease that COVID-19 represents, including autoimmune outcomes in affected patients.

Keywords: COVID-19; heparin-induced thrombocytopenia; platelet factor 4/heparin antibodies.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies / immunology*
  • Anticoagulants / adverse effects*
  • Anticoagulants / immunology
  • COVID-19 / complications*
  • COVID-19 / immunology
  • Heparin / adverse effects*
  • Heparin / immunology
  • Humans
  • Platelet Activation / drug effects
  • Platelet Factor 4 / immunology*
  • SARS-CoV-2 / immunology
  • Thrombocytopenia / chemically induced*
  • Thrombocytopenia / complications*
  • Thrombocytopenia / immunology


  • Antibodies
  • Anticoagulants
  • Platelet Factor 4
  • Heparin