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 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: 12 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 mAb 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.