Damage-associated cellular markers in the clinical and pathogenic profile of vaccine-induced immune thrombotic thrombocytopenia

Abrams, S. T. et al. (2024) Damage-associated cellular markers in the clinical and pathogenic profile of vaccine-induced immune thrombotic thrombocytopenia. Journal of Thrombosis and Haemostasis, 22(4), pp. 1145-1153. (doi: 10.1016/j.jtha.2023.12.008) (PMID:38103733)

Abstract

Background: Adenoviral vector-based COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT) is rare but carries significant risks of mortality and long-term morbidity. The underlying pathophysiology of severe disease is still not fully understood. The objectives were to explore the pathophysiological profile and examine for clinically informative biomarkers in patients with severe VITT. Methods: Twenty-two hospitalized patients with VITT, 9 pre- and 21 post-ChAdOx1 vaccine controls, were recruited across England, United Kingdom. Admission blood samples were analyzed for cytokine profiles, cell death markers (lactate dehydrogenase and circulating histones), neutrophil extracellular traps, and coagulation parameters. Tissue specimens from deceased patients were analyzed. Results: There were strong immune responses characterized by significant elevations in proinflammatory cytokines and T helper 1 and 2 cell activation in patients with VITT. Markers of systemic endothelial activation and coagulation activation in both circulation and organ sections were also significantly elevated. About 70% (n = 15/22) of patients met the International Society for Thrombosis and Haemostasis criteria for disseminated intravascular coagulation despite negligible changes in the prothrombin time. The increased neutrophil extracellular trap formation, in conjunction with marked lymphopenia, elevated lactate dehydrogenase, and circulating histone levels, indicates systemic immune cell injury or death. Both lymphopenia and circulating histone levels independently predicted 28-day mortality in patients with VITT. Conclusion: The coupling of systemic cell damage and death with strong immune-inflammatory and coagulant responses are pathophysiologically dominant and clinically relevant in severe VITT.

• Item Type: Articles
• Additional Information: This study is funded by the Liverpool University Hospitals National Health Service (NHS) Foundation Trust and the Department of Health and Social Care and is supported by the National Institute for Health Research (NIHR135073).
• Keywords: Vaccine-induced immune thrombocytopaenia and thrombosis (VITT), lactate dehydrogenase (LDH), circulating histones, neutrophil extracellular traps (NETs), disseminated intravascular coagulation (DIC).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McGuinness, Dr Dagmara and Moxon, Dr Christopher and Johnson, Miss Carla
• Authors: Abrams, S. T., Du, M., Shaw, R. J., Johnson, C., McGuinness, D., Schofield, J., Yong, J., Turtle, L., Nicolson, P. L.R., Moxon, C., Wang, G., and Toh, C.-H.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Journal of Thrombosis and Haemostasis
• Publisher: Elsevier
• ISSN: 1538-7933
• ISSN (Online): 1538-7836
• Published Online: 14 December 2023
• Copyright Holders: Copyright © 2023 The Author(s)
• First Published: First published in Journal of Thrombosis and Haemostasis 22(4):1145-1153
• Publisher Policy: Reproduced under a Creative Commons license