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.
Keywords: COVID-19; heparin; platelet factor 4; thrombocytopenia; thrombosis.
【저자키워드】 COVID-19, heparin, thrombocytopenia, platelet factor 4, thrombosis., 【초록키워드】 Treatment, antibodies, IgG, platelet activation, thrombosis, antibody, monoclonal antibody, Platelets, heparin, Antigen, serum, Critically ill, sera, Platelet, thrombocytopenia, antigen tests, platelet factor 4, COVID-19 patients, marker, Anticoagulants, Adverse reaction, COVID-19 patient, critically ill COVID-19 patients, heparin-induced thrombocytopenia, functional test, functional tests, confirmation, serum/plasma, cornerstone, fraction, positive, overdiagnosis, inhibitory, COVID-19 sera, HIPA, overtreatment, tested, caused, investigated, remained, clinically, inhibit, nine, unlikely, functional, clinically suspected, reactivity, purified, activating, 【제목키워드】 IgG antibody, COVID-19 patient,