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

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.

• Authors: Justine Brodard, Johanna A Kremer Hovinga, Pierre Fontana, Jan-Dirk Studt, Yves Gruel, Andreas Greinacher
• Journal: Journal of thrombosis and haemostasis : JTH (J Thromb Haemost) Vol. 19 Issue 5 Pg. 1294-1298 (05 2021) ISSN: 1538-7836 [Electronic] England
• PMID: 33550713 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.

Chemical References

• Anticoagulants
• Immunoglobulin G
• Platelet Factor 4
• Heparin

Topics

• Anticoagulants
• Blood Platelets
• COVID-19
• Heparin (adverse effects)
• Humans
• Immunoglobulin G
• Platelet Factor 4
• SARS-CoV-2