抗血小板因子4/肝素抗体与全身炎症性疾病和血栓形成障碍中血小板活化的相关性：来自COVID-19大流行的见解

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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引用次数: 0

摘要

在COVID-19大流行之后，人们对抗血小板因子4 (PF4) -肝素复合物（抗PF4/H）抗体的兴趣增加，这使它们成为免疫血栓形成的关键因素。目的研究抗pf4 /H抗体在COVID-19期间和疫苗接种后的作用，特别是在全身性炎症性疾病（SID）患者中。方法回顾性分析伴有和不伴有疑似肝素性血小板减少症（HIT）的COVID-19患者、疫苗诱导的免疫性血小板减少症（VITT）患者以及对照组和SID患者接种COVID-19疫苗后抗pf4 /H抗体的存在及其诱导血小板活化的能力。结果无论疾病严重程度如何，COVID-19期间抗pf4 /H抗体水平均未见显著升高。尽管在大流行期间观察到的HIT疑似病例增加了两倍，但HIT诊断没有相应增加。此外，即使在SID患者中，接种疫苗后抗pf4 /H水平也没有显著增加。通过可溶性p选择素水平和基于血小板微泡生成的流式细胞术测量，在COVID-19或疫苗接种队列中检测到的阳性抗pf4 /H抗体均未诱导血小板活化。最后，在VITT患者中，与HIT患者不同，抗pf4 /H水平与血小板微泡测定密切相关，与可溶性p选择素水平适度相关。结论我们的研究发现COVID-19患者或疫苗接种后抗pf4 /H抗体无显著增加，包括SID患者。然而，在VITT患者中，而在HIT患者中，这些抗体与血小板活化相关。这一发现表明，抗pf4 /H抗体在VITT的病理生理中起着不同的作用，但在HIT/VITT怀疑的明确背景之外，它们的作用有限。

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

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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