Antithrombotic Efficacy and Bleeding Risks of Vaccine-Induced Immune Thrombotic Thrombocytopenia Treatments
Current guidelines for treating vaccine-induced immune thrombotic thrombocytopenia (VITT) recommend non-heparin anticoagulants and intravenous immunoglobulin (IVIg). However, the efficacy of these treatments remains uncertain due to a lack of comparative clinical trials or animal studies. A recent study proposed danaparoid and heparin as potential VITT therapies due to their ability to disrupt VITT IgG-PF4 binding. Here, we examined the effects of various anticoagulants (including unfractionated (UF) heparin, danaparoid, bivalirudin, fondaparinux, and argatroban), IVIg, and the FcγRIIa receptor-blocking antibody, IV.3, in relation to VITT pathophysiology. Our investigation focused on VITT IgG-PF4 binding, platelet activation, thrombocytopenia, and thrombosis. Danaparoid, at therapeutic doses, was the sole anticoagulant that reduced VITT IgG-PF4 binding, verified by purified anti-PF4 specific VITT IgG. Low-dose UF heparin (<2 U/mL) augmented VITT IgG binding to PF4 on platelets. While d