PB1202 - Monitoring the persistence of vaccine-induced immune thrombotic thrombocytopenia (VITT) antibodies and their pathogenicity

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Christine S M Lee, PhD

Postdoctoral Research Fellow
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
TB

Timothy Brighton

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

Sanjeev Chunilal

Haematologist
Monash Health
Melbourne, Victoria, Australia
EF

Emmanuel J. Favaloro

Principal Scientist
Charles Sturt University, NSW Health Pathology, Sydney Centres for Thrombosis and Haemostasis
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
HT

Huyen Tran

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

Vivien M. Chen, Phd FRACP FRCPA

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

Background: The putative mechanism for vaccine-induced immune thrombotic thrombocytopenia (VITT) following ChAdOx1 nCoV-19 vaccination involves pathological anti-PF4 platelet-activating antibodies driving thrombosis and thrombocytopenia. Reports suggest platelet-activating antibodies decline within 12 weeks despite persistence of anti-PF4 by ELISA (Schönborn et al). Optimal duration of anticoagulation remains unclear. The Australian-New Zealand guidance recommends repeat testing of patients with serologically-confirmed VITT at 3, 6 and 12 months.

Aims: To determine rate of persistence of anti-PF4 ELISA compared with functional platelet-activating tests in VITT.

Methods: We conducted a prospective study of clinicopathological adjudicated VITT patients (thrombocytopenic with D-dimer levels >5x ULN and thrombosis within 4-43 days of ChAdOx1 nCoV-19 vaccination) with a positive functional assay at diagnosis who had follow-up VITT testing. 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) or PF4-serotonin release assay.

Results: 14 confirmed VITT patients (7 females, 7 males; median age 62.5 years [range, 40-80]) underwent follow-up testing, median follow-up of 12 weeks (range, 3-24). Median time to return a negative functional test was 12 weeks (range, 4-16) with platelet-activating antibodies persistent at 24 weeks in two patients. Median time to negative ELISA was not reached. During follow-up, 9 of 14 patients became negative by functional assay while anti-PF4 antibodies persisted in 8 of 12 (Figure 1). 93% of patients received a documented second vaccination (Comirnaty, median interval 16 weeks [range, 11-28]) and 71% have received an mRNA booster with no reported adverse events.

Conclusion(s): Platelet-activating antibodies were persistent in 54% of tested patients at 12 weeks and anti-PF4 ELISA remained positive in the majority. Anti-PF4 antibodies persist longer than functional platelet-activating antibodies in VITT. Whether the decline in platelet-activating antibodies allows withdrawal of anticoagulation in these patients is unclear but could be a useful guide.