Abstract Number: PB0035
Meeting: ISTH 2022 Congress
Background: Vaccines against SARS-CoV-2 virus reduce morbidity and mortality of the pandemic. But with millions of people vaccinated in a short period of time, even very rare side effects like the clotting disorder vaccine-induced thrombotic thrombocytopenia (VITT) became apparent. We recently identified an increase in procoagulant platelets in these patients.
Aims: Investigation of the impact of procoagulant platelets in thrombus formation.
Methods: 8 patients (4 female, 4 male) who were hospitalized with suspected thrombotic complications 5 to 16 days after ChAdOx1 nCoV-19 vaccination were included in this study. The blood samples were analyzed by using enzyme immune assays, flow cytometry, ex vivo thrombus formation assay and heparin-induced platelet aggregation assay.
Results: The median age was 38 years. All patients had thrombocytopenia at admission. Three had a fatal outcome and five were successfully treated. All sera from VITT patients contained high titer antibodies against platelet factor 4 (PF4) [OD:3.0±0.68] with the ability to activate platelets in the HIPA assay (8/8). Sera from VITT patients induced significant increase in procoagulant markers (P-selectin [CD62P] and phosphatidylserine externalization) [% CD62P/PS positive PLTs: 40.82±7.02] compared to COVID-19 patients [% CD62P/PS positive PLTs: 15.71±7.70]. The generation of procoagulant platelets was PF4 dependent. The formation of procoagulant platelets could be significantly reduced by use of the monoclonal IV.3 [% CD62P/PS positive PLTs: 1.05±0.21]; p=0.0001 antibody as well as IVIG [% CD62P/PS positive PLTs: 1.01±0.36]; p=0.0001. In thrombus formation model, IgGs from VITT patients induced increase platelet surface area (Mean % SAC±SEM: 10.38±1.30) compared to control IgG, which was inhibited by IVIG (4.08±0.96), p= 0.001.
Conclusion(s): Our ex vivo microfluidic thrombus formation model supports the significance of procoagulant platelet in the pathogenesis of VITT. It may offer significant clinical implications and therapeutic options like evaluation of IVIG as a recommended therapy or other drugs for treatment of clinical picture of VITT.
To cite this abstract in AMA style:Althaus K, Singh A, Pelzl L, Zlamal J, Marini I, Backchoul T. Increased thrombus formation via procoagulant platelets in vaccine induced thrombotic thrombocytopenia (VITT) [abstract]. https://abstracts.isth.org/abstract/increased-thrombus-formation-via-procoagulant-platelets-in-vaccine-induced-thrombotic-thrombocytopenia-vitt/. Accessed October 1, 2023.
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