A Review on Recommended Mechanisms in Thrombocytopenia and Thrombosis Following ChAdOx1 nCoV-19 Vaccination

ChAdOx1 nCov-19 vaccine is a viral vector-based vaccine with desirable protection (about 70.4% two weeks after the second dose). There were few reports on thrombocytopenia associated with thrombotic events shortly after ChAdOx1 nCov-19 vaccination. However, the exact pathophysiologic mechanism of this vaccine-induced thrombotic complication has not been yet elucidated. Vaccine induced thrombotic thrombocytopenia syndrome (VITTS), is associated with the detection of anti-PF4 antibodies, and is not still linked to the previous exposure to heparin.

In the current review, based on relevantly reported cases, possible mechanisms are suggested which provide a relationship between the results of anti-platelet factor 4 (anti-PF4) antibody assays, previous exposure to heparin, and the involved mechanisms of post-vaccination thrombocytopenia and thrombotic events, which might help the experts for selection of the appropriate therapeutic measures.

Possibly involved mechanisms in VITTS after ChAdOx1 nCoV-19 vaccination include binding of anti-PF4 antibodies to heparin/PF4 complex or to receptor binding domain (RBD) protein/PF4 complex. Additionally, binding of anti-RBD antibodies to RBD protein/PF4 complex could be considered as another mechanism. Finally, anti-RBD or anti-PF4 antibodies may bind to heparin/RBD protein/PF4 complex. Binding of either of the mentioned antibodies to these complexes via the Fc/ Angiotensin-converting enzyme 2 (ACE2) receptors can cause activation/removal of platelets leading to thrombocytopenia and thrombosis.

The suggested mechanisms in this article provide a relationship between the results of anti-PF4 antibody assays, previous exposure to heparin, and the involved mechanisms of post-vaccination thrombocytopenia and thrombotic events, which might help the experts for selection of the therapeutic measures.