Fig. 1.

Mechanisms of thrombosis and thrombocytopenia after vaccination against COVID-19. Both adenovirus-vectored vaccine and messenger RNA (mRNA) vaccine induce spike protein production, which leads to the platelet factor 4 (PF4) release from platelets. In the case of vectored vaccine, DNA or other substances of the adenovirus binds to the PF4 as polyanion and form PF4/polyanion complex. After the conformational changes, PF4 expresses antigenicity, and the production of anti-PF4/polyanion antibody that leads to vaccine-induced immune thrombotic thrombocytopenia (VITT)/thrombosis with thrombocytopenia syndrome (TTS) is introduced. However, this reaction is unlikely to occur after mRNA vaccine administration because of the absence of polyanions. To provide antigenic PF4, polyanions such as DNA from the vector adenovirus and hexon protein in vectored vaccine are needed. Basically, ordinary RNA induces both inflammation and coagulation through the recognition by toll-like receptor 3, 7, 8, and retinoic acid-inducible gene I protein (RIG-I) and subsequent proinflammatory cytokine production. Although these unfavorable reactions are modulated significantly in mRNA vaccines, complete abolishment cannot be guaranteed. In addition, inflammation-induced thrombin, neutrophil extracellular traps (NETs), and damage-associated molecular patterns (DAMPs) potentially elicit platelet activation. PAR-1: protease-activated receptor 1.