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Scientific article
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English

COVID-19 patients often show high-titer non-platelet-activating anti-PF4/heparin IgG antibodies

Published inJournal of thrombosis and haemostasis, vol. 19, no. 5, p. 1294-1298
Publication date2021-05
First online date2021-04-07
Abstract

Background: Heparin-induced thrombocytopenia (HIT) is a severe adverse reaction to heparin caused by heparin-dependent, platelet-activating anti-platelet factor 4 (PF4)/heparin antibodies. Heparin is a cornerstone of treatment in critically ill COVID-19 patients. HIT antibodies can be detected by antigen tests and functional tests. Often strong reactivity in the antigen test is used as a surrogate marker for the presence of clinically relevant, platelet-activating antibodies. We observed an unexpectedly high percentage of COVID-19 patients, clinically suspected to have HIT, with high titer anti-PF4/heparin antibodies, but a negative functional test.

Objective: We investigated whether in COVID-19 patients a serum-derived factor inhibits the heparin-induced platelet activation test (HIPA).

Methods and results: Twelve COVID-19 patients with suspected HIT were tested. Three samples tested negative in all assays; nine samples tested positive by antigen tests, among which only three tested also positive by HIPA. When we spiked COVID-19 serum or control serum with the human HIT antibody like monoclonal antibody 5B9, reactivity of 5B9 remained the same. Also, the purified IgG fractions of COVID-19 sera testing strongly positive in the PF4/heparin antigen test but negative in the functional test did not show increased reactivity in the functional test in comparison to the original serum. Both results make a functionally inhibitory factor in the serum/plasma of COVID-19 patients highly unlikely.

Conclusion: COVID-19 patients often present with strong reactivity in PF4/heparin antigen tests without the presence of platelet-activating antibodies. Diagnosis of HIT requires confirmation of heparin-dependent, platelets activating antibodies to avoid overdiagnosis and overtreatment with non-heparin anticoagulants.

eng
Keywords
  • COVID-19
  • Heparin
  • Platelet factor 4
  • Thrombocytopenia
  • Thrombosis
  • Anticoagulants
  • Blood Platelets
  • COVID-19
  • Heparin / adverse effects
  • Humans
  • Immunoglobulin G
  • Platelet Factor 4
  • SARS-CoV-2
Funding
  • Deutsche Forschungsgemeinschaft - [374031971 - TRR 240]
Citation (ISO format)
BRODARD, Justine et al. COVID-19 patients often show high-titer non-platelet-activating anti-PF4/heparin IgG antibodies. In: Journal of thrombosis and haemostasis, 2021, vol. 19, n° 5, p. 1294–1298. doi: 10.1111/jth.15262
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Article (Published version)
Identifiers
ISSN of the journal1538-7836
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Creation09/19/2022 3:03:00 PM
First validation09/19/2022 3:03:00 PM
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