Page 142 - 2021_06-Haematologica-web

Ferrata Storti Foundation
Haematologica 2021 Volume 106(8):2170-2179
Hemostasis
Antibody-mediated procoagulant platelets in SARS-CoV-2-vaccination associated immune thrombotic thrombocytopenia
Karina Althaus,1,2* Peter Möller,3* Günalp Uzun,2 Anurag Singh,1 Annika Beck,3 Martin Bettag,4 Hans Bösmüller,5 Martina Guthoff,6 Franziska Dorn,7 Gabor C. Petzold,8 Hans Henkes,9 Nils Heyne,6 Hassan Jumaa,10 Kornelia Kreiser,3 Caroline Limpach,11 Beate Luz,12 Matthias Maschke,13 Janis A. Müller,14 Jan Münch,14 Simon Nagel,15 Bernd Pötzsch,16 Jens Müller,16 Christoph Schlegel,17 Andreas Viardot,18 Hansjörg Bäzner,19 Marc Wolf,19 Lisann Pelzl,1 Verena Warm,5 Winfried A. Willinek,20 Jochen Steiner,21 Nicole Schneiderhan-Marra,22 Dominik Vollherbst,15 Ulrich J. Sachs,23 Falko Fend5# and Tamam Bakchoul1,2#
1Institute for Clinical and Experimental Transfusion Medicine, Medical Faculty of Tübingen, Tübingen University Hospital, Tübingen; 2Center for Clinical Transfusion Medicine, Tübingen University Hospital, Tübingen; 3Institute for Pathology, Ulm University Hospital, Ulm; 4Department of Neurosurgery, Krankenhaus der Barmherzigen Brüder Trier, Trier; 5Institute for Pathology and Neuropathology, Tübingen University Hospital, Tübingen; 6Department of Internal Medicine IV, Section of Nephrology and Hypertension, Tübingen University Hospital, Tübingen; 7Department of Neuroradiology, Bonn University Hospital, Bonn; 8Section of Vascular Neurology, University Hospital Bonn; 9Department of Neuroradiology, Klinikum Stuttgart, Stuttgart; 10Institute for Immunology, Ulm University Hospital, Ulm; 11Department of Neurology, Krankenhaus der Barmherzigen Brüder Trier, Trier; 12Institute of Transfusion Medicine, Klinikum Stuttgart, Stuttgart; 13Department of Neurology, Krankenhaus der Barmherzigen Brüder Trier, Trier; 14Institute of Molecular Virology, Ulm University Medical Center, Ulm; 15Department of Neuroradiology, Heidelberg University Hospital, Heidelberg; 16Institute for Experimental Hematology and Transfusion Medicine, Bonn; 17Ulm University Hospital, Ulm; 18Internal Medicine III, Ulm University Hospital, Ulm; 19Department of Neurology, Klinikum Stuttgart, Stuttgart; 20Department of Radiology, Krankenhaus der Barmherzigen Brüder Trier, Trier; 21Anesthesiology and Intensive Care Medicine, Tübingen University Hospital, Tübingen; 22Natural and Medical Sciences Institute, University of Tübingen, Reutlingen and 23Department of Thrombosis and Hemostasis and Institute of Immunology and Transfusion Medicine, Giessen, Germany
*KA and PM contributed equally as co-first authors. #FF and TB contributed equally as co-senior authors.
ABSTRACT
The COVID-19 pandemic has resulted in significant morbidity and mortality worldwide. In order to prevent severe infection, mass COVID-19 vaccination campaigns with several vaccine types are cur- rently underway. We report pathological and immunological findings in eight patients who developed vaccine-induced immune thrombotic throm- bocytopenia (VITT) after administration of SARS-CoV-2 vaccine ChAdOx1 nCoV-19. We analyzed patient material using enzyme immune assays, flow cytometry and heparin-induced platelet aggregation assay and performed autopsies on two fatal cases. Eight patients (five females, three males) with a median age of 41.5 years (range, 24-53) were referred to us with suspected thrombotic complications 6 to 20 days after ChAdOx1 nCoV-19 vaccina- tion. All patients had thrombocytopenia at admission. Patients had a median platelet count of 46.5x109/L (range, 8-92). Three had a fatal outcome and five were successfully treated. Autopsies showed arterial and venous throm- boses in various organs and the occlusion of glomerular capillaries by hya- line thrombi. Sera from VITT patients contain high-titer antibodies against platelet factor 4 (PF4) (optical density [OD] 2.59±0.64). PF4 antibodies in VITT patients induced significant increase in procoagulant markers (P- selectin and phosphatidylserine externalization) compared to healthy volun- teers and healthy vaccinated volunteers. The generation of procoagulant platelets was PF4 and heparin dependent. We demonstrate the contribution of antibody-mediated platelet activation in the pathogenesis of VITT.
Correspondence:
TAMAM BAKCHOUL
tamam.bakchoul@med.uni-tuebingen.de
FALKO FEND
falko.fend@med.uni-tuebingen.de
Received: April 16, 2021. Accepted: May 11, 2021. Pre-published: May20,2021.
https://doi.org/10.3324/haematol.2021.279000
©2021 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
2170
haematologica | 2021; 106(8)
ARTICLE