Relevance of anti–platelet factor 4/heparin antibodies and platelet activation in systemic inflammatory diseases and thrombosis disorders: insight from the COVID-19 pandemic

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis Pub Date : 2025-01-01 DOI:10.1016/j.rpth.2025.102701

Nicolas Gendron , Dominique Helley , Johannes Thaler , Dorothée Faille , Christine Le Beller , Maxime Gruest , Jérôme Hadjadj , Aurélien Philippe , Faris Zeco , Marie Courbebaisse , Luc Darnige , Wafa Amara , Leyla Calmette , Beatrice Parfait , Claire Auditeau , Richard Chocron , Lina Khider , Laetitia Mauge , Olivier Espitia , Gérard Friedlander , David M. Smadja

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Abstract

Background

The increased interest in anti–platelet factor 4 (PF4)–heparin complex (anti-PF4/H) antibodies following the COVID-19 pandemic has established them as crucial players in immunothrombosis.

Objectives

We aimed to investigate the involvement of anti-PF4/H antibodies during COVID-19 and after vaccination, particularly in patients with systemic inflammatory disease (SID).

Methods

This retrospective study analyzed the presence of anti-PF4/H antibodies and their ability to induce platelet activation in COVID-19 patients with and without suspected heparin-induced thrombocytopenia (HIT), vaccine-induced immune thrombotic thrombocytopenia (VITT) patients, and in controls and SID patients following COVID-19 vaccination.

Results

No significant increase in anti-PF4/H antibody levels was observed during COVID-19 regardless of disease severity. Despite a 2-fold increase in HIT suspicion observed during the pandemic, there was no corresponding increase in HIT diagnoses. Additionally, no significant increase in anti-PF4/H levels was noted after vaccination, even in SID patients. None of the positive anti-PF4/H antibodies detected in COVID-19 or vaccination cohorts induced platelet activation, measured by soluble P-selectin levels and flow cytometry-based on platelet microvesicle generation. Finally, in VITT patients, unlike in HIT patients, anti-PF4/H levels were strongly associated with platelet microvesicle assay and moderately with soluble P-selectin levels.

Conclusion

Our study found no significant increase in anti-PF4/H antibodies in COVID-19 or after vaccination, including in SID patients. However, in VITT patients, but not in HIT patients, these antibodies were correlated with platelet activation. This finding suggests that anti-PF4/H antibodies play a different role in the pathophysiology of VITT but that their interest is limited outside clear contexts of HIT/VITT suspicion.

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