VPB0111 - Thrombocytopenia and Thrombosis associated with AstraZeneca ChAdOx1 nCoV-19 Vaccination – results of Australian centralized clinical triage system and functional assay testing system

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: Virtual

Presenting Author(s)

VC

Vivien M. Chen, Phd FRACP FRCPA

Group Leader, Staff Specialist Haematologist
ANZAC Research Institute, University of Sydney
Sydney, New South Wales, Australia

Co-Author(s)

LC

Lisa Clarke

Consultant Haematologist
Department of Haematology, Concord Repatriation General Hospital; Australian Red Cross Lifeblood, Sydney Adventist Hospital
Concord, New South Wales, Australia
Christine S M Lee, PhD

Postdoctoral Research Fellow
ANZAC Research Institute, University of Sydney
Sydney, New South Wales, Australia
FP

Freda Passam

Group Leader
Haematology Research Group, Charles Perkins Centre, University of Sydney
Sydney, New South Wales, Australia
DD

Dea Donikian

Hospital Scientist
Department Haematology, New South Wales Health Pathology, Prince of Wales Hospital
Sydney, New South Wales, Australia
MK

Mayuko Kondo

Hospital Scientist
Department Haematology, New South Wales Health Pathology, Prince of Wales Hospital
Sydney, New South Wales, Australia
RB

Robert Bird

Director of Haematology
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia
Philip Choi, MBBS PhD FRACP FRCPA

Haematologist
Canberra Hospital
Canberra, Australian Capital Territory, Australia
Ibrahim Tohidi-Esfahani, BMed FRACP FRCPA

Clinical research Fellow
Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UK
London, England, United Kingdom
Dominic Pepperell, BSc (Hons) MRCP UK FRCP UK FRACP FRCPA

Haematologist
Fiona Stanley Hospital
Perth, Western Australia, Australia
CT

Chee Wee TAN

Clinical Director
SA Pathology, Adelaide, SA, Australia
Adelaide, South Australia, Australia
SC

Sanjeev Chunilal

Haematologist
Monash Health
Melbourne, Victoria, Australia
HT

Huyen Tran

Professor
Australian Centre for Blood Diseases, Monash University
Melbourne, Victoria, Australia
TB

Timothy Brighton

Professor
Prince of Wales Hospital
Sydney, New South Wales, Australia

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.

Aims: To evaluate the triage strategy based upon clinical presentation, thrombocytopenia and D-Dimer used to direct VITT testing.

Methods: 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.

Results: 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.