Article ; Online: COVID-19 patients often show high-titer non-platelet-activating anti-PF4/heparin IgG antibodies.
Journal of thrombosis and haemostasis : JTH
2021 Volume 19, Issue 5, Page(s) 1294–1298
Abstract: ... percentage of COVID-19 patients, clinically suspected to have HIT, with high titer anti-PF4/heparin ... by heparin-dependent, platelet-activating anti-platelet factor 4 (PF4)/heparin antibodies. Heparin is ... 19 patients often present with strong reactivity in PF4/heparin antigen tests without the presence ...
| 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. |
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| MeSH term(s) | Anticoagulants ; Blood Platelets ; COVID-19 ; Heparin/adverse effects ; Humans ; Immunoglobulin G ; Platelet Factor 4 ; SARS-CoV-2 | ||||||||||
| Chemical Substances | Anticoagulants ; Immunoglobulin G ; Platelet Factor 4 (37270-94-3) ; Heparin (9005-49-6) | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2021-04-07 | ||||||||||
| Publishing country | England | ||||||||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | ||||||||||
| ZDB-ID | 2112661-6 | ||||||||||
| ISSN | 1538-7836 ; 1538-7933 | ||||||||||
| ISSN (online) | 1538-7836 | ||||||||||
| ISSN | 1538-7933 | ||||||||||
| DOI | 10.1111/jth.15262 | ||||||||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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