Anti-PF4-antibodies in VITT the Greifswald findings - Andreas Greinacher S. Felix
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Anti-PF4-antibodies in VITT
the Greifswald
S. Felix
findings
Andreas Greinacher
Institut für Transfusionsmedizin
Universitätsmedizin Greifswald, Germany
1456
Disclosures for Andreas Greinacher
Research Support/P.I. ASPEN
Employee No relevant conflicts of interest to declare
Consultant Instrumentation Laboratory; ASPEN; BioKit;
MacoPharma; Chromatec
Major Stockholder No relevant conflicts of interest to declare
Speakers Bureau No relevant conflicts of interest to declare
Honoraria No relevant conflicts of interest to declare
Scientific Advisory Board Instrumentation Laboratory; ASPEN; BioKit
Classified as internal/staff & contractors by the European Medicines Agency
Structure • PF4 antibodies in VITT • PF4 binding partners and VITT • VITT-like abs independent of Covid-19 vaccination
PF4/polyanion IgG ELISA VITT-patients Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. N Engl J Med. 2021
PF4/polyanion antibody ELISA VITT - Patients
Platton S, et al JTH 2021 Vayne C et al NEJM 2021
Summary PF4/polyanion lab tests for VITT:
ORIGINAL ARTICLEs
Anti-PF4 testing for vaccine-induced immune 1. ELISA plate based anti-PF4/polyanion assays work but
thrombocytopenia and thrombosis (VITT): Results with different sensitivities
from a NEQAS, ECAT and SSC collaborative exercise in 2. Rapid tests, antigen coated on beads are insensitive
385 centers worldwide (false neg)
Christopher Reilly-Stitt,Ian Jennings,Steve Kitchen,Mike Makris,Piet Meijer,Moniek de
Maat,Marie Scully,Tamam Bakchoul,Isobel D. Walker
First published: 23 May 2022
Nature, prepublished July 07 2021
PF4-ELISA reactive antibodies are rather frequent
Thiele T et al, BLOOD 2021
The first VITT patients, March 17, 2021 Warkentin TE, Greinacher A, Laboratory testing of VITT, Semin Hematol 2022
Washed platelet assays VITT - Patients
Greinacher A et al NEJM 2021
Crossreactivity of anti-spike antibodies with PF4?
Greinacher A et al Blood. 2021 Oct 7;138(14):1269-1277.Schönborn L., Seck S, Thiele T., Warkentin TE, Greinacher A.
New Engl J Med 2022; June 27 epub
Observation in humans
11 VITT patients developed Covid-19
anti-PF4 antibodies before and after Covid-19
Conclusion
Human in-vivo evidence that VITT is neither
related to the spike protein nor to SARS-CoV2VITT antibodies are transient
Schönborn L. et al. NEJM 2021; 385(19):1815-1816
Schönborn et al. BLOOD 2022; ;139(12):1903-1907Clonal restriction of VITT abs
Genetic predisposition?
1. Kanack A, Bayas A, George G, et al. Monoclonal and
oligoclonal anti-Platelet Factor 4 antibodies mediate
VITT. Blood. 2022 epub.
2. Wang JJ, Armour BL, Ms, Chataway T, et al. Vaccine-
induced immune thrombotic thrombocytopenia
(VITT) is mediated by a stereotyped clonotypic
antibody. Blood. 2022 epub
3. Greinacher A, Nimmerjahn F commentary BLOOD
2022, in pressClassified as internal/staff & contractors by the European Medicines Agency Greinacher A et al. BLOOD 09/2021
PF4 Hexon VITT IgG
Greinacher A et al. BLOOD 09/2021C D E
Vaccine Vaccine + PF4 Vaccine + PF4
stained for adenovirus proteins stained for PF4
Greinacher A et al. BLOOD 09/2021PF4 binding partners in VITT
Greinacher A et al. BLOOD 09/2021
Michalik S Haematologica. 2022 Jan 20. doi:10.3324/haematol.2021.280154.published 02.12.21
VITT beyond vaccination? Greinacher A et al Haematologica. 2021 Dec 30. doi: 10.3324/haematol.2021.280366.
Greinacher A et al Haematologica. 2021 Dec 30. doi: 10.3324/haematol.2021.280366.
Summary • VITT is caused by anti-PF4 antibodies • VITT antibodies strongly activate platelets, no cofactor required • The binding partner of PF4 triggering VITT antibodies is still unknown • VITT antibodies are not triggered by SARS-CoV2 or spike protein • VITT antibodies are transient • VITT like antibodies can occur independent of Covid-19 vaccination
Kathleen Selleng Karin Weisser Antje Vogelgesang Jan Wesche Paul A. Kyrle Agnes Flöel Stefan Handtke Sabine Eichinger Piero Lovreglio Raghavendra Palankar Martina Wolff Angela Stufano Konstanze Aurich Carlo Zaninetti Rolf Marschalek Michael Lalk Lena Ulm Brigitte Keller-Stanislawski Karen Methling Nils-Olaf Hübner Emil Reisinger Uwe Völker Karsten Becker Markus Funk Christian Hentschker Julia Mayerle Farid Salih Stephan Michalik Sven Reiche Siegfried Kohler Leif Steil Andrea Aebischer Christiana Franke Linda Schönborn Maximilian Muenchhoff Martin Möckel Martin Beer Johannes C. Hellmuth Thomas Dörner Kati Franzke Oliver T. Keppler Hans C. Bauknecht Chandini Rangaswamy Daniel Duerschmied Christian Pille Reiner K. Mailer Achim Lother Jan A. Graw Thomas Thiele Siegbert Rieg Angelika Alonso Stefan Kochanek Meinrad Paul Gawaz Johann Pelz Lea Krutzke Karin Anne Lydia Mueller Hauke Schneider Florian Siegerist Christian S. Scheer Antonios Bayas Nicole Endlich Matthias Napp Monika Christ Theodore E. Warkentin Klaus Hahnenkamp Joji B. Kuramatsu Thomas Renne Guglielmo Lucchese Matthias Endres
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