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


Abrams, Simon T ORCID: 0000-0003-3949-2455, Du, Min, Shaw, Rebecca J ORCID: 0000-0002-1190-7244, Johnson, Carla, McGuinness, Dagmara, Schofield, Jeremy ORCID: 0000-0003-2761-913X, Yong, Jun, Turtle, Lance ORCID: 0000-0002-0778-1693, Nicolson, Phillip LR, Moxon, Christopher et al (show 2 more authors) (2023) Damage-associated cellular markers in the clinical and pathogenic profile of vaccine-induced immune thrombotic thrombocytopenia. Journal of thrombosis and haemostasis : JTH, 22 (4). S1538-7836(23)00873-5-S1538-7836(23)00873-5. ISSN 1538-7933, 1538-7836

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Abstract

<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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: Article
Uncontrolled Keywords: Humans, Thrombosis, Purpura, Thrombocytopenic, Idiopathic, Thrombocytopenia, Lymphopenia, Lactate Dehydrogenases, Histones, Vaccines, COVID-19 Vaccines
Divisions: Faculty of Health & Life Sciences
Faculty of Health & Life Sciences > Inst. Infection, Vet & Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 19 Jan 2024 11:24
Last Modified: 22 May 2026 22:48
DOI: 10.1016/j.jtha.2023.12.008
Open Access URL: https://doi.org/10.1016/j.jtha.2023.12.008
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3177911
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