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Persistence of Ad26.COV2.S‐associated vaccine‐induced immune thrombotic thrombocytopenia (VITT) and specific detection of VITT antibodies

Rare cases of COVID‐19 vaccinated individuals develop anti‐platelet factor 4 (PF4) antibodies that cause thrombocytopenia and thrombotic complications, a syndrome referred to as vaccine‐induced immune thrombotic thrombocytopenia (VITT). Currently, information on the characteristics and persistence o...

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Autores principales: Kanack, Adam J., Singh, Bandana, George, Gemlyn, Gundabolu, Krishna, Koepsell, Scott A., Abou‐Ismail, Mouhamed Yazan, Moser, Karen A., Smock, Kristi J., Green, David, Major, Ajay, Chan, Clarence W., Wool, Geoffrey D., Reding, Mark, Ashrani, Aneel A., Bayas, Antonios, Grill, Diane E., Padmanabhan, Anand
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986571/
https://www.ncbi.nlm.nih.gov/pubmed/35132672
http://dx.doi.org/10.1002/ajh.26488
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author Kanack, Adam J.
Singh, Bandana
George, Gemlyn
Gundabolu, Krishna
Koepsell, Scott A.
Abou‐Ismail, Mouhamed Yazan
Moser, Karen A.
Smock, Kristi J.
Green, David
Major, Ajay
Chan, Clarence W.
Wool, Geoffrey D.
Reding, Mark
Ashrani, Aneel A.
Bayas, Antonios
Grill, Diane E.
Padmanabhan, Anand
author_facet Kanack, Adam J.
Singh, Bandana
George, Gemlyn
Gundabolu, Krishna
Koepsell, Scott A.
Abou‐Ismail, Mouhamed Yazan
Moser, Karen A.
Smock, Kristi J.
Green, David
Major, Ajay
Chan, Clarence W.
Wool, Geoffrey D.
Reding, Mark
Ashrani, Aneel A.
Bayas, Antonios
Grill, Diane E.
Padmanabhan, Anand
author_sort Kanack, Adam J.
collection PubMed
description Rare cases of COVID‐19 vaccinated individuals develop anti‐platelet factor 4 (PF4) antibodies that cause thrombocytopenia and thrombotic complications, a 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 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. Here we demonstrate that while Ad26.COV2.S‐associated VITT patients are uniformly strongly positive in PF4‐polyanion enzyme‐linked immunosorbent assays (ELISAs); they are frequently negative in the serotonin release assay (SRA). The PF4‐dependent p‐selectin expression assay (PEA) that uses platelets treated with PF4 rather than heparin 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 x 10(3)/µL) 6 months after acute presentation. From an epidemiological perspective, differentiating VITT from spontaneous HIT, another entity that develops in the absence of proximate heparin exposure, and HIT is important, but currently available PF4‐polyanion ELISAs and functional assay are non‐specific and detect all three conditions. Here, we report that a novel un‐complexed PF4 ELISA specifically differentiates VITT, secondary to both Ad26.COV2.S and ChAdOx1 nCoV‐19, from both spontaneous HIT, HIT and commonly‐encountered HIT‐suspected patients who are PF4/polyanion ELISA‐positive but negative in functional assays. In summary, Ad26.COV2.S‐associated VITT antibodies are persistent, and the un‐complexed PF4 ELISA appears to be both sensitive and specific for VITT diagnosis.
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spelling pubmed-89865712022-05-09 Persistence of Ad26.COV2.S‐associated vaccine‐induced immune thrombotic thrombocytopenia (VITT) and specific detection of VITT antibodies Kanack, Adam J. Singh, Bandana George, Gemlyn Gundabolu, Krishna Koepsell, Scott A. Abou‐Ismail, Mouhamed Yazan Moser, Karen A. Smock, Kristi J. Green, David Major, Ajay Chan, Clarence W. Wool, Geoffrey D. Reding, Mark Ashrani, Aneel A. Bayas, Antonios Grill, Diane E. Padmanabhan, Anand Am J Hematol Research Articles Rare cases of COVID‐19 vaccinated individuals develop anti‐platelet factor 4 (PF4) antibodies that cause thrombocytopenia and thrombotic complications, a 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 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. Here we demonstrate that while Ad26.COV2.S‐associated VITT patients are uniformly strongly positive in PF4‐polyanion enzyme‐linked immunosorbent assays (ELISAs); they are frequently negative in the serotonin release assay (SRA). The PF4‐dependent p‐selectin expression assay (PEA) that uses platelets treated with PF4 rather than heparin 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 x 10(3)/µL) 6 months after acute presentation. From an epidemiological perspective, differentiating VITT from spontaneous HIT, another entity that develops in the absence of proximate heparin exposure, and HIT is important, but currently available PF4‐polyanion ELISAs and functional assay are non‐specific and detect all three conditions. Here, we report that a novel un‐complexed PF4 ELISA specifically differentiates VITT, secondary to both Ad26.COV2.S and ChAdOx1 nCoV‐19, from both spontaneous HIT, HIT and commonly‐encountered HIT‐suspected patients who are PF4/polyanion ELISA‐positive but negative in functional assays. In summary, Ad26.COV2.S‐associated VITT antibodies are persistent, and the un‐complexed PF4 ELISA appears to be both sensitive and specific for VITT diagnosis. John Wiley & Sons, Inc. 2022-02-21 2022-05 /pmc/articles/PMC8986571/ /pubmed/35132672 http://dx.doi.org/10.1002/ajh.26488 Text en © 2022 Wiley Periodicals LLC. This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.
spellingShingle Research Articles
Kanack, Adam J.
Singh, Bandana
George, Gemlyn
Gundabolu, Krishna
Koepsell, Scott A.
Abou‐Ismail, Mouhamed Yazan
Moser, Karen A.
Smock, Kristi J.
Green, David
Major, Ajay
Chan, Clarence W.
Wool, Geoffrey D.
Reding, Mark
Ashrani, Aneel A.
Bayas, Antonios
Grill, Diane E.
Padmanabhan, Anand
Persistence of Ad26.COV2.S‐associated vaccine‐induced immune thrombotic thrombocytopenia (VITT) and specific detection of VITT antibodies
title Persistence of Ad26.COV2.S‐associated vaccine‐induced immune thrombotic thrombocytopenia (VITT) and specific detection of VITT antibodies
title_full Persistence of Ad26.COV2.S‐associated vaccine‐induced immune thrombotic thrombocytopenia (VITT) and specific detection of VITT antibodies
title_fullStr Persistence of Ad26.COV2.S‐associated vaccine‐induced immune thrombotic thrombocytopenia (VITT) and specific detection of VITT antibodies
title_full_unstemmed Persistence of Ad26.COV2.S‐associated vaccine‐induced immune thrombotic thrombocytopenia (VITT) and specific detection of VITT antibodies
title_short Persistence of Ad26.COV2.S‐associated vaccine‐induced immune thrombotic thrombocytopenia (VITT) and specific detection of VITT antibodies
title_sort persistence of ad26.cov2.s‐associated vaccine‐induced immune thrombotic thrombocytopenia (vitt) and specific detection of vitt antibodies
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986571/
https://www.ncbi.nlm.nih.gov/pubmed/35132672
http://dx.doi.org/10.1002/ajh.26488
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