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Title: Population-wide persistent hemostatic changes after vaccination with ChAdOx1-S
Authors: de Laat, Bas
Stragier, Hendrik
de Laat-Kremers, Romy
Ninivaggi, Marisa
Thiessen, Steven
Van Pelt, Kristien
Roest, Mark
Huskens, Dana
De Jongh , Raf
Fivez, Tom
ten Cate, Hugo
Issue Date: 2022
Source: Frontiers in Cardiovascular Medicine, 9 (Art N° 966028)
Abstract: Various vaccines were developed to reduce the spread of the Severe Acute Respiratory Syndrome Cov-2 (SARS-CoV-2) virus. Quickly after the start of vaccination, reports emerged that anti-SARS-CoV-2 vaccines, including ChAdOx1-S, could be associated with an increased risk of thrombosis. We investigated the hemostatic changes after ChAdOx1-S vaccination in 631 health care workers. Blood samples were collected 32 days on average after the second ChAdOx1-S vaccination, to evaluate hemostatic markers such as D-dimer, fibrinogen, alpha 2-macroglobulin, FVIII and thrombin generation. Endothelial function was assessed by measuring Von Willebrand Factor (VWF) and active VWF. IL-6 and IL-10 were measured to study the activation of the immune system. Additionally, SARS-CoV-2 anti-nucleoside and anti-spike protein antibody titers were determined. Prothrombin and fibrinogen levels were significantly reduced after vaccination (-7.5% and -16.9%, p < 0.0001). Significantly more vaccinated subjects were outside the normal range compared to controls for prothrombin (42.1% vs. 26.4%, p = 0.026) and antithrombin (23.9% vs. 3.6%, p = 0.0010). Thrombin generation indicated a more procoagulant profile, characterized by a significantly shortened lag time (-11.3%, p < 0.0001) and time-to-peak (-13.0% and p < 0.0001) and an increased peak height (32.6%, p = 0.0015) in vaccinated subjects compared to unvaccinated controls. Increased VWF (+39.5%, p < 0.0001) and active VWF levels (+24.1 %, p < 0.0001) pointed toward endothelial activation, and IL-10 levels were significantly increased (9.29 pg/mL vs. 2.43 pg/mL, p = 0.032). The persistent increase of IL-10 indicates that the immune system remains active after ChAdOx1-S vaccination. This could trigger a pathophysiological mechanism causing an increased thrombin generation profile and vascular endothelial activation, which could subsequently result in and increased risk of thrombotic events.
Notes: de Laat, B (corresponding author), Synapse Res Inst, Dept Funct Coagulat, Maastricht, Netherlands.; de Laat, B (corresponding author), Synapse Res Inst, Dept Data Anal & Artificial Intelligence, Maastricht, Netherlands.
Keywords: ChAdOx1-S;COVID-19;thrombin generation;vaccination;hemostasis
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ISSN: 2297-055X
e-ISSN: 2297-055X
DOI: 10.3389/fcvm.2022.966028
ISI #: 000840609700001
Rights: 2022 de Laat, Stragier, de Laat-Kremers, Ninivaggi, Mesotten, Thiessen, Van Pelt, Roest, Penders, Vanelderen, Huskens, De Jongh, Laenen, Fivez, ten Cate, Heylen, Heylen and Steensels. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Category: A1
Type: Journal Contribution
Appears in Collections:Research publications

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