Following vector-based vaccinations against the severe acute respiratory syndrome coronavirus 2, life-threatening thrombotic events in uncommon locations have been observed. It was known as vaccine-induced immune thrombotic thrombocytopenia (VITT).
VITT has a similar etiology to heparin-induced thrombocytopenia (HIT) and is linked with platelet-activating antibodies (Abs) against platelet factor 4 (PF4). As a result, current guidelines recommend nonheparin anticoagulants for treating VITT patients. Researchers used an ex vivo model for thrombus formation as well as in vitro tests to examine Ab binding and platelet activation to investigate the interactions of heparin, danaparoid, fondaparinux, and argatroban with VITT–Ab/PF4 complexes. They discovered that VITT patients’ immunoglobulin Gs (IgGs) cause more adherent platelets/thrombus development than IgGs from healthy controls. The procoagulant activity of VITT IgGs was successfully reduced in this ex vivo flow-based model by danaparoid, argatroban, and heparin. On the other hand, Heparin and danaparoid blocked IgG binding to PF4 and successfully dissociated the generated PF4/IgG complexes.
Fondaparinux decreased procoagulant platelet percent thrombus formation in vitro but did not affect platelet aggregation. Argatroban, on the other hand, did not affect procoagulant platelets or aggregation but greatly prevented VITT-mediated thrombus development. The findings suggested that negatively charged anticoagulants can disrupt VITT–Ab/PF4 interactions, which might be used to minimize Ab-mediated problems in VITT. However, the findings need to be validated in a clinical context before investigators can recommend anticoagulant therapy in VITT patients.