"1 Introduction
... Soon after the implementation of large-scale SARS-CoV-2 vaccination, thrombotic events were reported as possible side effects. First reports described a pattern of thrombosis after vaccination with the vector-based ChAdOx1 nCoV-19 vaccine, associated with platelet factor 4 autoantibodies, a low platelet count, increased D-dimer, and decreased fibrinogen levels, and was named vaccine-induced thrombotic thrombocytopenia [VITT]. In addition, increased rates of venous thrombotic events without thrombocytopenia were reported in the weeks after vector-based (ChAdOx1 nCoV-19 or Ad26.COV2.S) and (to a lesser extent) mRNA-based vaccines (BNT162b2 or mRNA-1273)...
The aim of the present study was to assess the change proxies for a prothrombotic change, ie, levels of coagulation factor (F)VIII, fibrinogen, D-dimer, and thrombin generation parameters following mRNA-1273 vaccination by dose as well as the association between these changes and the inflammatory response...
2.1 Trial design
This study was a secondary analysis of an open-label, randomized controlled trial at the Leiden University Medical Center in the Netherlands...
3 Results
... [A] total of 123 (82%) participants were included in the analyses of coagulation... 112 participants ... were included in the analysis of the association between coagulation and inflammation...
4 Discussion
SARS-CoV-2 vaccination with full-dose i.m. or fractional-dose (one-fifth of standard dose) i.d. [intradermal] of the mRNA-1273 vaccine results in a transient prothrombotic state as evidenced by changes in peak height, ETP [endogenous thrombin potential], levels of fibrinogen, and D-dimer. Particularly, the systemic inflammatory response was most pronounced in participants receiving the full dose of the vaccine intramuscularly as compared with the participants receiving the fractional dose intradermally. These changes in coagulation were associated with the inflammatory response.
Although no association was seen between the change in coagulation (D36-D1) and the inflammatory response after vaccination (D36-D1) in the primary coagulation endpoint (peak height), this was observed for multiple other coagulation endpoints, ie, lag time, ETP, time to peak, the start tail time, fibrinogen, and FVIII. Particularly, the change in ETP was positively associated with the change in inflammation. This is most likely due to a longer time to complete inhibition of thrombin generation than a stronger and faster propagation of thrombin caused by inflammation (relatively stronger association of start tail time with inflammation than lag time or time to peak or peak height)...
Prior studies that evaluated coagulation parameters in SARS-CoV-2 vaccinated individuals using an unvaccinated control group also reported a change in the thrombohemorrhagic balance toward hypercoagulability."
© 2024 The Author(s). Published by Elsevier Inc. on behalf of International Society on Thrombosis and Haemostasis.
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