Platelet Surface Protein Expression and Reactivity upon TRAP Stimulation after BNT162b2 Vaccination

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces a coagulopathy characterized by platelet activation and a hypercoagulable state with an increased incidence of cardiovascular events. The viral spike protein S has been reported to enhance thrombosis formation, stimulate platelets to release procoagulant factors, and promote the formation of platelet–leukocyte aggregates even in absence of the virus. Although SARS-CoV-2 vaccines induce spike protein overexpression to trigger SARS-CoV-2-specific immune protection, thrombocyte activity has not been investigated in this context. Here, we provide the first phenotypic platelet characterization of healthy human subjects undergoing BNT162b2 vaccination. Using mass cytometry, we analyzed the expression of constitutive transmembrane receptors, adhesion proteins, and platelet activation markers in 12 healthy donors before and at five different time points within 4 weeks after the first BNT162b2 administration. We measured platelet reactivity by stimulating thrombocyte activation with thrombin receptor-activating peptide. Activation marker expression (P-selectin, LAMP-3, LAMP-1, CD40L, and PAC-1) did not change after vaccination. All investigated constitutive transmembrane proteins showed similar expressions over time. Platelet reactivity was not altered after BNT162b2 administration. Activation marker expression was significantly lower compared with an independent cohort of mild symptomatic COVID-19 patients analyzed with the same platform. This study reveals that BNT162b2 administration does not alter platelet protein expression and reactivity.

Head-to-head comparison of four COVID-19 vaccines on platelet activation, coagulation and inflammation. The TREASURE study

“…The expression of platelet activation markers –P-selectin, activated GpIIbIIIa, TF, platelet-granulocyte and platelet-monocyte aggregate formation, total and TF-positive MV formation- was analyzed by flow cytometry on whole blood samples, thus in the absence of any pre-analytical manipulation. Results showed the absence of any change in the classical platelet activation parameters following vaccination, confirming previous data [19] , [20] , [21] , [22] . Interestingly a mild, although statistically significant, increase in platelet TF-dependent prothrombotic potential was observed only in ChAdOx1-S Vaxzevria immunized subjects.…”

Platelet–Leucocyte Aggregates as Novel Biomarkers in Cardiovascular Diseases

“…It is probably the most up-to-date field of interest in PLA research. Although SARS-CoV-2 vaccines induce spike protein overexpression, vaccination with BNT162b2 does not alter platelet protein expression, and reactivity [ 184 ] but SARS-CoV-2 infection induces PLA formation rather than platelet–platelet aggregates [ 185 ], and PLA are accused of forming blood clots in severe COVID-19 [ 186 ]. Altogether, they create a new concept of PLA’ pathomechanism in COVID-19 cardiovascular complications, which deserves separate review.…”

Platelet and immune signature associated with a rapid response to the BNT162b2 mRNA COVID‐19 vaccine

“…Klug and colleagues recently reported that platelet reactivity was unchanged after BNT162b2 vaccine administration, when platelets were stimulated with TRAP, a G-protein coupled receptor (GPCR) agonist. 35 A possible reason ITAM, but not GPCR, signalling needs to be primed is that the platelet ITAM receptors, GPVI and CLEC-2, are necessary to secure vascular integrity at sites of inflammation 36 while the GPCRs for thrombin are dispensable for inflammation-mediated hemostasis. 37 Another reason priming of ITAM-dependent P-selectin exposure might be beneficial in healthy individuals is that P-selectin facilitates platelet-leukocyte interactions.…”

“…However, we found that vaccinated subjects were more responsive to GPVI stimulation compared to controls, as if the vaccine had a priming effect on ITAM signalling. Klug and colleagues recently reported that platelet reactivity was unchanged after BNT162b2 vaccine administration, when platelets were stimulated with TRAP, a G‐protein coupled receptor (GPCR) agonist 35 . A possible reason ITAM, but not GPCR, signalling needs to be primed is that the platelet ITAM receptors, GPVI and CLEC‐2, are necessary to secure vascular integrity at sites of inflammation 36 while the GPCRs for thrombin are dispensable for inflammation‐mediated hemostasis 37 …”