Inflammation and Platelet Activation After COVID-19 Vaccines - Possible Mechanisms Behind Vaccine-Induced Immune Thrombocytopenia and Thrombosis

Average: 5 (1 vote)
Controlled Clinical Trial
. 2021 Nov 23;12:779453.
 doi: 10.3389/fimmu.2021.779453. eCollection 2021.
Free PMC article


Introduction of vaccines against COVID-19 has provided the most promising chance to control the world-wide COVID-19 pandemic. However, the adenovirus-vector based Oxford/AstraZeneca [ChAdOx1] (AZ) and Johnson & Johnson [Ad26.CoV2.S] COVID-19 vaccines have been linked with serious thromboembolic events combined with thrombocytopenia, denominated Vaccine-induced Immune Thrombocytopenia and Thrombosis (VITT). The pathogenesis of COVID-19 VITT remain incompletely understood; especially the initial events that trigger platelet activation, platelet factor (PF)4 release, complex formation and PF4 antibody production are puzzling. This is a prospective study investigating the impact of different COVID-19 vaccines on inflammation (CRP, TNF-α, IL-1β, IL-6, IL-8, IL-10), vascular endothelial activation (syndecan-1, thrombomodulin, E-selectin, ICAM-1, ICAM-3, VCAM-1), platelet activation (P-selectin, TGF-β, sCD40L) and aggregation (Multiplate® impedance aggregometry), whole blood coagulation (ROTEM®), thrombin generation and PF4 antibodies to reveal potential differences between AZ and mRNA vaccines in individuals without VITT. The study included 80 (55 AZ and 55 mRNA) vaccinated individuals and 55 non-vaccinated age- and gender matched healthy controls. The main findings where that both vaccines enhanced inflammation and platelet activation, though AZ vaccination induced a more pronounced increase in several inflammatory and platelet activation markers compared to mRNA vaccination and that post-vaccination thrombin generation was higher following AZ vaccination compared to mRNA vaccination. No difference in neither the PF4 antibody level nor the proportion of individuals with positive PF4 antibodies were observed between the vaccine groups. This is the first study to report enhanced inflammation, platelet activation and thrombin generation following AZ vaccination compared to mRNA vaccination in a head-to-head comparison. We speculate that specific components of the AZ adenovirus vector may serve as initial trigger(s) of (hyper)inflammation, platelet activation and thrombin generation, potentially lowering the threshold for a cascade of events that both trigger complications related to excessive inflammation, platelet and coagulation activation as observed in epidemiological studies and promote development of VITT when combined with high-titer functionally active PF4 antibodies.

Keywords: COVID-19; TTS; VITT; platelet factor 4; thrombocytopenia; thrombosis; vaccines.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Figure 1

Figure 1 

Study design. Eighty participants (n=80)…

 Figure 2

Figure 2 

Inflammation markers pre- and post-vaccination…

 Figure 3

Figure 3 

Vascular endothelial activation markers pre-…

 Figure 4

Figure 4 

Platelet activation markers pre- and…

Similar articles

Cited by 4 articles


    1. Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. Thrombotic Thrombocytopenia After ChAdOx1 nCov-19 Vaccination. N Engl J Med (2021) 384:2092–101. doi: 10.1056/NEJMoa2104840 - DOI PMC PubMed
    1. Schultz NH, Sørvoll IH, Michelsen AE, Munthe LA, Lund-Johansen F, Ahlen MT, et al. . Thrombosis and Thrombocytopenia After ChAdOx1 nCoV-19 Vaccination. N Engl J Med (2021) 384:2124–30. doi: 10.1056/NEJMoa2104882 - DOI PMC PubMed
    1. Blauenfeldt RA, Kristensen SR, Ernstsen SL, Kristensen CCH, Simonsen CZ, Hvas A-M. Thrombocytopenia With Acute Ischemic Stroke and Bleeding in a Patient Newly Vaccinated With an Adenoviral Vector-Based COVID-19 Vaccine. J Thromb Haemost (2021) 19:1771–5. doi: 10.1111/jth.15347 - DOI PMC PubMed
    1. See I, Su JR, Lale A, Woo EJ, Guh AY, Shimabukuro TT, et al. . US Case Reports of Cerebral Venous Sinus Thrombosis With Thrombocytopenia After Ad26.Cov2.S Vaccination, March 2 to April 21, 2021. JAMA (2021) 325:2448–56. doi: 10.1001/jama.2021.7517 - DOI PMC PubMed
    1. Muir K-L, Kallam A, Koepsell SA, Gundabolu K. Thrombotic Thrombocytopenia After Ad26.COV2.S Vaccination. N Engl J Med (2021) 384:1964–5. doi: 10.1056/NEJMc2105869 - DOI PMC PubMed