ArticleJournal of thrombosis and haemostasis : JTH2021
COVID-19 patients often show high-titer non-platelet-activating anti-PF4/heparin IgG antibodies.
Article in Journal of thrombosis and haemostasis : JTH, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 2 of them syntheses that pooled it.
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Who cites it
47 citing papers in PubMed, 2 syntheses or guidelines pooled it, 73 citations in OpenAlex.
- Significance of heparin induced thrombocytopenia (HIT) in COVID-19: a systematic review and meta-analysis.Journal of thrombosis and thrombolysis · 2023Pooled it
- Heparin-induced thrombocytopenia in patients with COVID-19: a systematic review and meta-analysis.Blood advances · 2021Pooled it
- Prothrombotic antibodies targeting the spike protein's receptor-binding domain in severe COVID-19.Blood · 2025Article
- Platelet Factor 4: A Mysterious Chemokine in Inflammatory Regulation Diseases.Journal of inflammation research · 2025Review
- Relevance of anti-platelet factor 4/heparin antibodies and platelet activation in systemic inflammatory diseases and thrombosis disorders: insight from the COVID-19 pandemic.Research and practice in thrombosis and haemostasis · 2025Article
- Thromboembolism after Astra Zeneca COVID-19 vaccine: Not always PF4- antibody mediated.Human vaccines & immunotherapeutics · 2023Article
- Article
- Immune complexes as culprits of immunopathology in severe COVID-19.Medical microbiology and immunology · 2023Review
- From Co-Infections to Autoimmune Disease via Hyperactivated Innate Immunity: COVID-19 Autoimmune Coagulopathies, Autoimmune Myocarditis and Multisystem Inflammatory Syndrome in Children.International journal of molecular sciences · 2023Review
- Anti-PF4 antibodies associated with disease severity in COVID-19.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Preexisting anti-PF4 antibodies are not further triggered upon vaccination with SARS-CoV-2 vector vaccines in a cohort of 400 health care workers.Thrombosis research · 2022Article
- Complementary Sets of Autoantibodies Induced by SARS-CoV-2, Adenovirus and Bacterial Antigens Cross-React with Human Blood Protein Antigens in COVID-19 Coagulopathies.International journal of molecular sciences · 2022Article
- The potential impact of Covid-19 on the capacity of routine laboratory tests to detect heparin-induced thrombocytopenia.Thrombosis journal · 2022Article
- Proteomics of fibrin amyloid microclots in long COVID/post-acute sequelae of COVID-19 (PASC) shows many entrapped pro-inflammatory molecules that may also contribute to a failed fibrinolytic system.Cardiovascular diabetology · 2022Article
- Anticoagulation Strategies in Critically Ill Patients With SARS-CoV-2 Infection: The Role of Direct Thrombin Inhibitors.Journal of cardiothoracic and vascular anesthesia · 2022Observational
- Platelet Dysregulation in the Pathobiology of COVID-19.Hamostaseologie · 2022Review
- ABO O blood group as a risk factor for platelet reactivity in heparin-induced thrombocytopenia.Blood · 2022Article
- SARS-CoV-2 Infection in Patients with a History of VITT.The New England journal of medicine · 2022Article
- Cerebral venous sinus thrombosis after adenovirus-vectored COVID-19 vaccination: review of the neurological-neuroradiological procedure.Neuroradiology · 2022Review
- Case report: cerebral sinus vein thrombosis in two patients with AstraZeneca SARS-CoV-2 vaccination.Journal of neurology · 2022Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundHeparin-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.
objectiveWe investigated whether in COVID-19 patients a serum-derived factor inhibits the heparin-induced platelet activation test (HIPA). METHODS AND
resultsTwelve 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.
conclusionCOVID-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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