OC 02.4 - Persistence of Ad26.COV2.S-associated VITT and specific detection of VITT antibodies

Saturday, July 9, 2022

1:45 PM – 2:00 PM

Location: S11B

Presentation Format: In-Person

Presenting Author(s)

anand padmanabhan, MD

Associate Professor
Mayo Clinic
Rochester, Minnesota, United States

Co-Author(s)

adam J. Kanack, PhD

Post doctoral fellow
Mayo Clinic
rochester, Minnesota, United States
BS

Bandana Singh

Post doctoral fellow
Mayo Clinic
rochester, Minnesota, United States
GG

Gemlyn George

Physician
Univ of Colorado
Denver, Colorado, United States
KG

Krishna Gundabolu

Physician
University of Nebraska
Omaha, Nebraska, United States
SK

Scott Koepsell

Physician
University of Nebraska
Omaha, Nebraska, United States
YA

Yazan Abou-Ismail

Physician
University of Utah
Salt Lake City, Utah, United States
KM

Karen Moser

Physician
University of Utah
Salt Lake City, Utah, United States
KS

Kristi Smock

Department of Pathology and ARUP Laboratories
University of Utah
Salt Lake City, Utah, United States
DG

David Green

Physician
New York University Langone Health
New York, New York, United States
AM

Ajay Major

Physician
University of Chicago
Chicago, Illinois, United States
CC

Clarence Chan

Physician
University of Chicago
Chicago, Illinois, United States
GW

Geoffrey Wool

Physician
University of Chicago
Chicago, Illinois, United States
MR

Mark T. Reding

Professor and Director
Center for Bleeding and Clotting Disorders, University of Minnesota, Minneapolis, MN, USA
Minneapolis, Minnesota, United States
AA

Aneel Ashrani

Physician
Mayo Clinic
Rochester, Minnesota, United States
AB

Antonios Bayas

Physician
University of Augsburg
Augsburg, Bayern, Germany
DG

Diane Grill

Biostatistician
Mayo Clinic
Rochester, Minnesota, United States

Background: Some COVID-19 vaccinated individuals develop anti-platelet factor 4 (PF4) antibodies that cause thrombocytopenia and thrombosis; a rare syndrome referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT). Currently, information on the characteristics and persistence of anti-PF4 antibodies that cause VITT after Ad26.COV2.S vaccination is limited, and available PF4-polyanion enzyme-linked immunosorbent assays (ELISAs) and functional diagnostic assays fail to differentiate Ad26.COV2.S and ChAdOx1 nCoV-19-associated VITT from similar clinical disorders, namely heparin-induced thrombocytopenia (HIT) and spontaneous HIT.

Aims: Evaluate the persistence of anti-PF4 antibodies in Ad26.COV2.S-associated VITT and correlate findings with clinical and laboratory variables such as thrombosis and platelet counts. Develop/investigate laboratory tools that differentiate VITT antibodies from HIT and spontaneous HIT.

Methods: Blood samples from VITT and HIT patient cohorts were tested in antigen-based and functional assays and correlated with clinical and laboratory features.

Results: While Ad26.COV2.S-associated VITT patients were strongly positive in PF4-polyanion ELISAs; they were frequently negative in the serotonin release assay (4 of 8 tested patients were negative). In contrast, the PF4-dependent p-selectin expression assay (PEA) that uses PF4-treated platelets consistently diagnosed Ad26.COV2.S-associated VITT. Most Ad26.COV2.S-associated VITT antibodies persisted for >5 months in PF4-polyanion ELISAs, while the PEA became negative earlier. Two patients had otherwise unexplained mild persistent thrombocytopenia (140-150,000/uL) six months after acute presentation. No recurrence of thrombosis was noted. Additionally, a novel un-complexed PF4 ELISA specifically differentiated VITT secondary to Ad26.COV2.S and ChAdOx1 nCoV-19 vaccination, from spontaneous HIT and HIT (Fig 1A- PF4/polyanion ELISA; Fig 1B- Un-complexed PF4 ELISA; closed black circles- Ad26.COV2.S-associated VITT; closed red circle- ChAdOx1 nCoV-19-associated VITT; *** p< 0.001; **** p< 0.0001). Its specificity was further confirmed by testing commonly-encountered HIT-suspected patient samples that are PF4/polyanion ELISA-positive but negative in functional assays (1A-1B).

Conclusion(s): Ad26.COV2.S-associated VITT antibodies are persistent, and the un-complexed PF4 ELISA appears to be both sensitive and specific for VITT diagnosis.