COVID-19 patients often show high-titer non-platelet-activating anti-PF4/heparin IgG antibodies. Brodard, J., Kremer Hovinga, J. A., Fontana, P., Studt, J., Gruel, Y., & Greinacher, A. Journal of thrombosis and haemostasis: JTH, February, 2021. doi abstract bibtex 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.
@article{brodard_covid-19_2021,
title = {{COVID}-19 patients often show high-titer non-platelet-activating anti-{PF4}/heparin {IgG} antibodies},
issn = {1538-7836},
doi = {10.1111/jth.15262},
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.},
language = {eng},
journal = {Journal of thrombosis and haemostasis: JTH},
author = {Brodard, Justine and Kremer Hovinga, Johanna A. and Fontana, Pierre and Studt, Jan-Dirk and Gruel, Yves and Greinacher, Andreas},
month = feb,
year = {2021},
pmid = {33550713},
pmcid = {PMC8013750},
keywords = {COVID-19, heparin, platelet factor 4, thrombocytopenia, thrombosis},
}
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{"_id":"yj2KAX4gqSRH6DTEr","bibbaseid":"brodard-kremerhovinga-fontana-studt-gruel-greinacher-covid19patientsoftenshowhightiternonplateletactivatingantipf4hepariniggantibodies-2021","author_short":["Brodard, J.","Kremer Hovinga, J. A.","Fontana, P.","Studt, J.","Gruel, Y.","Greinacher, A."],"bibdata":{"bibtype":"article","type":"article","title":"COVID-19 patients often show high-titer non-platelet-activating anti-PF4/heparin IgG antibodies","issn":"1538-7836","doi":"10.1111/jth.15262","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.","language":"eng","journal":"Journal of thrombosis and haemostasis: JTH","author":[{"propositions":[],"lastnames":["Brodard"],"firstnames":["Justine"],"suffixes":[]},{"propositions":[],"lastnames":["Kremer","Hovinga"],"firstnames":["Johanna","A."],"suffixes":[]},{"propositions":[],"lastnames":["Fontana"],"firstnames":["Pierre"],"suffixes":[]},{"propositions":[],"lastnames":["Studt"],"firstnames":["Jan-Dirk"],"suffixes":[]},{"propositions":[],"lastnames":["Gruel"],"firstnames":["Yves"],"suffixes":[]},{"propositions":[],"lastnames":["Greinacher"],"firstnames":["Andreas"],"suffixes":[]}],"month":"February","year":"2021","pmid":"33550713","pmcid":"PMC8013750","keywords":"COVID-19, heparin, platelet factor 4, thrombocytopenia, thrombosis","bibtex":"@article{brodard_covid-19_2021,\n\ttitle = {{COVID}-19 patients often show high-titer non-platelet-activating anti-{PF4}/heparin {IgG} antibodies},\n\tissn = {1538-7836},\n\tdoi = {10.1111/jth.15262},\n\tabstract = {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.\nOBJECTIVE: We investigated whether in COVID-19 patients a serum-derived factor inhibits the heparin-induced platelet activation test (HIPA).\nMETHODS 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.\nCONCLUSION: 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.},\n\tlanguage = {eng},\n\tjournal = {Journal of thrombosis and haemostasis: JTH},\n\tauthor = {Brodard, Justine and Kremer Hovinga, Johanna A. and Fontana, Pierre and Studt, Jan-Dirk and Gruel, Yves and Greinacher, Andreas},\n\tmonth = feb,\n\tyear = {2021},\n\tpmid = {33550713},\n\tpmcid = {PMC8013750},\n\tkeywords = {COVID-19, heparin, platelet factor 4, thrombocytopenia, thrombosis},\n}\n\n","author_short":["Brodard, J.","Kremer Hovinga, J. A.","Fontana, P.","Studt, J.","Gruel, Y.","Greinacher, A."],"key":"brodard_covid-19_2021","id":"brodard_covid-19_2021","bibbaseid":"brodard-kremerhovinga-fontana-studt-gruel-greinacher-covid19patientsoftenshowhightiternonplateletactivatingantipf4hepariniggantibodies-2021","role":"author","urls":{},"keyword":["COVID-19","heparin","platelet factor 4","thrombocytopenia","thrombosis"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://bibbase.org/zotero/ckelleyt","dataSources":["W5PhLT7vuF6ko8d7J","SeNAp632YK4DdmyJo","tTydwtpFKyvDpy8qn"],"keywords":["covid-19","heparin","platelet factor 4","thrombocytopenia","thrombosis"],"search_terms":["covid","patients","show","high","titer","non","platelet","activating","anti","pf4","heparin","igg","antibodies","brodard","kremer hovinga","fontana","studt","gruel","greinacher"],"title":"COVID-19 patients often show high-titer non-platelet-activating anti-PF4/heparin IgG antibodies","year":2021}