PB0055 - Comparison of five different PF4 dependant immunoassays in the diagnosis of Vaccine-induced Thrombotic Thrombocytopenia (VITT)

Background: Vaccination with ChAdOx1 Cov-19 can rarely cause a condition called Vaccine-induced Thrombotic Thrombocytopenia (VITT), characterised by acute thrombosis and thrombocytopenia, mediated by platelet-activating antibodies against Platelet factor 4 (PF4), which clinically mimics heparin-induced thrombocytopenia (HIT). VITT occurs between 4-42 days after vaccination unrelated to heparin exposure and is associated with elevated D-Dimer and high titre immunoglobulin-G (IgG) class anti-PF4 antibodies. The use of PF4/heparin immunoassays has been proposed as part of the diagnostic approach.

Aims: To compare and analyse five different types of immunoassays in suspected cases of VITT.

Methods: Blood samples from 21 patients suspected of having VITT were analysed using five different assays available for anti-PF4 testing. These assays were divided into three groups: 1) IgG-specific ELISA (Hyphen Biomed Zymutest HIA IgG); 2) polyspecific ELISA [IgG, IgA and IgM (IgGAM) Hyphen Biomed Zymutest HIA]; and 3) Rapid assays: a) polyspecific Diamed PaGIA gel, b) IgG-specific HemosIL AcuStar HIT-IgG and c) Latex Immuno assay (LIA) ACL-TOP. Results were interpreted as positive or negative using the manufacturers’ cut-offs.

Results: In our study of 21 suspected VITT cases, 6 were positive for IgG and IgGAM ELISA, suggesting the possibility of vaccine induced anti-PF4 antibodies. Five of the 6 cases were negative for all other rapid assays, while one was positive for PaGIA also. Two cases were positive only on LIA in ACL-TOP. Both cases had recent history of vaccination and thrombocytopenia but presented with bleeding manifestations rather than thrombosis. One patient was positive only for IgGAM ELISA. He was a renal transplant recipient with thrombocytopenia, but no evidence of thrombosis. The interval between vaccination and presentation was more than 3 months.

Conclusion(s): Anti-PF4 antibodies detected only on ELISAs and not on other platforms, suggest the possibility of VITT. In the appropriate clinical context, this could be viewed as laboratory “confirmation” of VITT.