Limb ischemia due to spontaneous heparin-induced thrombocytopenia as the primary presentation of acute COVID-19 infection

J Thromb Thrombolysis. 2022 Aug;54(2):367-371. doi: 10.1007/s11239-022-02676-8. Epub 2022 Jun 28.


Heparin-induced thrombocytopenia (HIT) occurs with the development of IgG antibodies that bind complexes of heparin and platelet factor 4 (PF4), which activate platelets and result in a profoundly prothrombotic condition. In rare instances, this syndrome develops in the absence of proximate heparin administration, referred to as spontaneous HIT, for which less than three dozen cases have been reported. Spontaneous HIT is considered a subtype of "autoimmune HIT" (aHIT), characterized by platelet activation in the serotonin release assay (SRA) without the addition of exogenous heparin. Here, we report spontaneous HIT as the presenting feature in a patient with 2019 coronavirus disease infection (COVID-19).A 66-year-old male presented with progressive leg pain and was found to have a platelet count of 39 × 109/L and multiple lower extremity arterial thromboses requiring fasciotomy and thrombectomy. He had no recent hospitalization, heparin exposure, vaccinations, or known thrombophilia. He had a strongly positive IgG-specific enzyme-linked immunosorbent assay for heparin-PF4 antibodies, and the SRA was strongly positive both with and without the addition of heparin. He was treated successfully with bivalirudin, intravenous immunoglobulin, and apixaban.

Keywords: COVID-19; Heparin; Immunoglobulins, Intravenous; Thrombocytopenia; Thrombosis.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Anticoagulants / adverse effects
  • COVID-19* / complications
  • Heparin / adverse effects
  • Humans
  • Immunoglobulin G
  • Immunologic Factors
  • Ischemia
  • Male
  • Platelet Factor 4
  • Thrombocytopenia* / chemically induced
  • Thrombocytopenia* / diagnosis


  • Anticoagulants
  • Immunoglobulin G
  • Immunologic Factors
  • Platelet Factor 4
  • Heparin