COVID-19 Vaccination and Vaccine-Induced Immune Thrombotic Thrombocytopenia

Close up of a mature man taking a vaccine in his doctors office
Researchers sought to determine the pathology behind possible vaccine-induced immune thrombocytopenia and thrombosis following COVID-19 vaccinations.

Researchers examined the pathology behind possible vaccine-induced immune thrombocytopenia and thrombosis following COVID-19 vaccinations using an adenovirus vector-based vaccine, implicating inflammation and platelet activation as playing roles in this process. The results of the study were published in Frontiers in Immunology.

The prospective study was the ENFORCE trial, a vaccine trial funded by the Danish Ministry of Health, and it provided a head-to-head comparison of outcomes with either an adenovirus vector-based vaccine or an mRNA-based vaccine. The evaluated adenovirus vector-based vaccine was the Oxford/AstraZeneca (AZ) ChAdOx1 vaccine, and the mRNA-based vaccines included both the Pfizer/BioNTech BNT162b2 and Moderna mRNA-1273 vaccines.

Study participants receiving vaccines provided blood samples from prior to and at multiple time points following vaccination. A group of nonvaccinated age- and sex-matched control individuals was also evaluated. Several hematologic parameters were examined, such as through biomarker, standard coagulation, platelet aggregation, whole blood coagulation, and thrombin generation analyses.

There were 80 participants who received COVID-19 vaccines included in the analysis, of whom 55 received ChAdOx1 vaccination and 25 who received either BNT162b2 or mRNA-1273 vaccination. There were also 55 participants in the control group. The median age was 49 years in both the vaccinated and nonvaccinated groups and 73% of participants were women in both of these groups.

Markers of inflammation and platelet activation were found to be enhanced in recipients of either type of vaccine following vaccination. However, vaccination with ChAdOx1 reportedly was reportedly associated with greater increases in certain biomarkers of inflammation and platelet activation, compared with what was seen with mRNA-based vaccines.

The median platelet count was higher with ChAdOx1 vaccination than with mRNA-based vaccination or without vaccination. The mRNA-based vaccination group had a higher median fibrinogen level following vaccination than the ChAdOx1 group did, and it was also higher than what was seen in the control group.

Both vaccinated groups showed evidence of higher platelet aggregation following vaccination than the control group did, based on COLtest results. Thromboelastometry analyses suggested clot formation also was stronger for both vaccinated groups than in the nonvaccinated group. Postvaccination thrombin generation was greater with ChAdOx1 than with mRNA-based vaccines, based on a shorter median lag time, shorter median time to peak thrombin generation, higher median peak thrombin concentration, and a higher median endogenous thrombin potential.

Platelet factor 4 (PF4) antibody levels were similar between the evaluated vaccinated groups. Additionally, PF4 antibody positivity was similar between vaccinated and nonvaccinated groups.

“The main findings were that the AZ vaccine induced a more pronounced increase in inflammation and platelet activation and higher thrombin generation compared to mRNA vaccines and that none of the vaccinated individuals developed PF4 antibodies,” the study investigators concluded in their report. They speculated that certain components of the adenovirus vector used in ChAdOx1 may be relevant to patterns seen in this study.


Ostrowski SR, Søgaard OS, Tolstrup M, et al. Inflammation and platelet activation after COVID-19 vaccines – possible mechanisms behind vaccine-induced immune thrombocytopenia and thrombosis. Front Immunol. 2021 Nov;12:779453. doi:10.3389/fimmu.2021.779453

This article originally appeared on Hematology Advisor