Thrombocytopenia and thrombosis associated with AstraZeneca ChAdOx1 nCoV-19 Vaccination-Results of Australian centralized clinical triage system and functional assay testing system

ABSTRACT

Background: As a severe, though rare complication of COVID-19 vaccination, vaccine induced immune thrombotic thrombocytopenia (VITT) emerged in 2021 as a public health issue affecting vaccine confidence. Australia pre-emptively instituted a nationally coordinated system for diagnosis and management incorporating state based immunoassays (ELISA) for PF4 antibodies and national centralised functional testing using three functional assays. Aim(s) To evaluate the triage strategy based upon clinical presentation, thrombocytopenia and D-Dimer used to direct VITT testing. Method(s) Consecutive cases presenting between April 1 and June 11, 2021 referred for VITT testing in Australia were assessed regarding clinical classification, immune-assay and functional assay results, thromboses and mortality according to triage category (Table 1). Functional testing proceeded for all triaged as Probable VITT , ELISA positive and unusual site thromboses positive patients if triaged Less likely , and only for quality assurance purposes if Much less likely VITT . Anti-PF4 antibodies were measured by IgG-specific ELISA (Asserachrom, Stago Diagnostics). Platelet-activating antibodies were assayed using whole blood procoagulant platelet flow cytometry assay (Lee et al), PF4-serotonin release assay or multiplate multiple electrode aggregation. Result(s) 92% of 52 patients with a final diagnosis of VITT supported by a positive antibody assay (immunological or functional) were triaged prior to VITT specific testing into the high probability category. 100% ELISA positive individuals within the high and intermediate clinical probability groups were supported by detection of a platelet activating antibody using a functional assay and 0% in the low probability group. 16% of clinical VITT patients without confirmation of anti-PF4 antibodies by ELISA had VITT diagnosis supported by functional assay in a final clinico-pathological adjudication. Conclusion(s) Triage of testing according to clinical probability of VITT based on clinical criteria and standard laboratory tests was helpful in directing testing in resource constrained period. Demonstration of platelet activating antibodies in functional assays significantly contributes to definition of the VITT syndrome. (Table Presented).