Observational studyBlood advances2025
Platelet-activating histone/antihistone IgG complexes in anti-PF4-negative thrombosis and thrombocytopenia syndrome.
Observational study in Blood advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04370119 (Screening for SARS-CoV-2-Infections and Monitoring of Serological Responses to SARS-CoV-2 in Healthcare Workers), which is not on this map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Screening for SARS-CoV-2-Infections and Monitoring of Serological Responses to SARS-CoV-2 in Healthcare Workers
Who cites it
9 citing papers in PubMed.
- A systematic review of vaccine-induced immune thrombosis and thrombocytopenia triggered by non-adenoviral vector vaccination: ultra-rare or non-existent?Haematologica · 2026Article
- Charge-driven antiviral responses enhance autoreactivity in severe COVID-19.Research square · 2026Article
- Non-PF4/heparin-binding, platelet-activating antibodies in heparin-induced thrombocytopenia.Blood · 2026Article
- Procoagulant platelets: linking coagulation and thromboinflammation in cardiovascular disease.Nature reviews. Cardiology · 2026Review
- Comparison of variably specific Bruton tyrosine kinase inhibitors on platelet aggregation mediated by Fcγ receptor (FcγR) IIa, glycoprotein VI, and platelet endothelial aggregation receptor (PEAR) 1: implications for Bruton tyrosine kinase inhibitors as antithrombotic therapy.Research and practice in thrombosis and haemostasis · 2026Article
- Atypical memory B cell clonal expansion and inflammatory programs associate with platelet-activating antibody development in COVID-19.JCI insight · 2026Article
- A novel evaluation indicator for pediatric fulminant myocarditis: diagnostic and prognostic value of the HALP score.BMC pediatrics · 2026Article
- VITT Pathophysiology: An Update.Vaccines · 2025Review
- Advances in our understanding of anti-PF4 related immunothrombosis.Frontiers in immunology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
abstractThrombosis and thrombocytopenia syndromes (TTS) describe immune-mediated thrombotic adverse reactions after vaccination against COVID-19. Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a well-known subentity of TTS, caused by adenovirus vector-based vaccines. VITT is mediated by anti-platelet factor 4 (PF4) immunoglobulin G (IgG) antibodies, activating platelets via Fc-γ IIa receptors (FcγRIIa). We describe clinical and serological features of 18 patients with anti-PF4/heparin enzyme-linked immunosorbent assay (ELISA)-negative TTS in temporal relationship to messenger RNA (mRNA)-based COVID-19 vaccination. Symptoms began at a median of 7 (range 1 - 61) days after vaccination. Patients showed thrombocytopenia (platelet count 59 × 103/μL; range, 0 to 127 × 103/μL); petechiae (n = 7), venous thromboembolism (n = 11), arterial thrombosis (n = 6), disseminated intravascular coagulation (n = 1), and combined arterial and venous thromboses (n = 1). Twelve sera-induced FcγRIIa-dependent and caspase-independent procoagulant activation of platelets indicated by phosphatidylserine exposure and CD62P expression. We found histones precipitated with IgG fractions of TTS sera. Antibodies binding to histones were found in 8 of 12 platelet-activating sera. Ex vivo-generated histone/antihistone IgG complexes strongly activated platelets via FcγRIIa, whereas antihistone IgG alone did not. Platelet autoantibodies were detected in 7 of 12 sera targeting glycoprotein (GP) IIb/IIIa (n = 5), GPIb/IX (n = 5), and GPIa/IIa (n = 3). However, sera containing platelet anti-GPIIb/IIIa autoantibodies activated also platelets from a patient with Glanzmann thrombasthenia, making it unlikely that these autoantibodies are causative for platelet activation. Finally, 2 of 114 healthy vaccinees developed antihistone antibodies after mRNA-based COVID-19 vaccination. Our data indicate a new subentity of TTS associated with platelet-activating histone/antihistone IgG complexes. Further studies are warranted to characterize the biological and clinical role of post-mRNA-based vaccination antihistone antibodies. The SeCo trial was registered at www.ClinicalTrials.gov as #NCT04370119.
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