Antiphospholipid antibodies and risk of post-COVID-19 vaccination thrombophilia: The straw that breaks the camel's back?

Highlights

• The coagulation pathway can be aberrantly activated during COVID-19 and, in rare cases, following COVID-19 vaccination.

• APL-induced immunothrombosis may be the unifying mechanism underlying COVID-19 and post-COVID-19 vaccination thrombophilia.

• ·COVID-19 vaccines may trigger de novoproduction of aPLs or induce a full-blown APS in asymptomatic aPL-positive individuals.

• Screening for aPLs is recommended prior to undergoing COVID-19 vaccination and between two consecutive vaccine doses.

Abstract

Antiphospholipid antibodies (aPLs), present in 1–5 % of healthy individuals, are associated with the risk of antiphospholipid syndrome (APS), which is the most common form of acquired thrombophilia. APLs may appear following infections or vaccinations and have been reported in patients with COronaVIrus Disease-2019 (COVID-19). However, their association with COVID-19 vaccination is unclear. Notably, a few cases of thrombocytopenia and thrombotic events resembling APS have been reported to develop in recipients of either adenoviral vector- or mRNA-based COVID-19 vaccines.

The aim of this review is therefore to speculate on the plausible role of aPLs in the pathogenesis of these rare adverse events.

Adenoviral vector-based vaccines can bind platelets and induce their destruction in the reticuloendothelial organs. Liposomal mRNA-based vaccines may instead favour activation of coagulation factors and confer a pro-thrombotic phenotype to endothelial cells and platelets. Furthermore, both formulations may trigger a type I interferon response associated with the generation of aPLs. In turn, aPLs may lead to aberrant activation of the immune response with participation of innate immune cells, cytokines and the complement cascade. NETosis, monocyte recruitment and cytokine release may further support endothelial dysfunction and promote platelet aggregation. These considerations suggest that aPLs may represent a risk factor for thrombotic events following COVID-19 vaccination, and deserve further investigations.