TY - JOUR
T1 - The ADAMTS13-von Willebrand factor axis in COVID-19 patients
AU - Mancini, Ilaria
AU - Baronciani, Luciano
AU - Artoni, Andrea
AU - Colpani, Paola
AU - Biganzoli, Marina
AU - Cozzi, Giovanna
AU - Novembrino, Cristina
AU - Boscolo Anzoletti, Massimo
AU - De Zan, Valentina
AU - Pagliari, Maria Teresa
AU - Gualtierotti, Roberta
AU - Aliberti, Stefano
AU - Panigada, Mauro
AU - Grasselli, Giacomo
AU - Blasi, Francesco
AU - Peyvandi, Flora
N1 - Funding Information:
This work was partially supported by the Italian Ministry of Health ‐ Bando Ricerca Corrente and partially financed by Italian fiscal contribution "5x1000" 2017 devolved to Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico.
Funding Information:
Dr. Mancini received honoraria for participating as a speaker at educational meetings organized by Instrumentation Laboratory and Sanofi‐Genzyme, outside the submitted work. Dr. Novembrino received honoraria for lectures from Instrumentation Laboratory, Roche, Bayer, Novonordisk, and Sobi, outside the submitted work. Dr. Gualtierotti reports personal fees from Biomarin and Takeda, outside the submitted work. Dr. Aliberti reports personal fees from Bayer Healthcare, Grifols, Astra Zeneca, Zambon, GlaxoSmithKline, Menarini, and ZetaCube Srl; grants from Fisher & Paykel; and grants and personal fees from Chiesi and INSMED, outside the submitted work. Dr. Grasselli received payment for lectures and travel/congress registration support from Getinge, Draeger Medical, Biotest, Fisher & Paykel, Thermofisher, and MSD, outside the submitted work. Dr. Blasi reports personal fees from Guidotti, Grifols, Menarini, Mundipharma, Novartis, and Zambon; grants from Bayer; and grants and personal fees from Astrazeneca, Chiesi, GlaxoSmithKline, INSMED, and Pfizer, outside the submitted work. Dr. Peyvandi is a scientific advisory member of Bioverativ, Roche, Sanofi‐Genzyme, and Sobi, outside the submitted work. The other authors do not have any conflict of interests to disclose.
Publisher Copyright:
© 2020 International Society on Thrombosis and Haemostasis
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - Background: Severe coronavirus disease 2019 (COVID-19) is characterized by an increased risk of thromboembolic events, with evidence of microthrombosis in the lungs of deceased patients. Objectives: To investigate the mechanism of microthrombosis in COVID-19 progression. Patients/Methods: We assessed von Willebrand factor (VWF) antigen (VWF:Ag), VWF ristocetin-cofactor (VWF:RCo), VWF multimers, VWF propeptide (VWFpp), and ADAMTS13 activity in a cross-sectional study of 50 patients stratified according to their admission to three different intensity of care units: low (requiring high-flow nasal cannula oxygenation, n = 14), intermediate (requiring continuous positive airway pressure devices, n = 17), and high (requiring mechanical ventilation, n = 19). Results: Median VWF:Ag, VWF:RCo, and VWFpp levels were markedly elevated in COVID-19 patients and increased with intensity of care, with VWF:Ag being 268, 386, and 476 IU/dL; VWF:RCo 216, 334, and 388 IU/dL; and VWFpp 156, 172, and 192 IU/dL in patients at low, intermediate, and high intensity of care, respectively. Conversely, the high-to-low molecular-weight VWF multimers ratios progressively decreased with increasing intensity of care, as well as median ADAMTS13 activity levels, which ranged from 82 IU/dL for patients at low intensity of care to 62 and 55 IU/dL for those at intermediate and high intensity of care. Conclusions: We found a significant alteration of the VWF-ADAMTS13 axis in COVID-19 patients, with an elevated VWF:Ag to ADAMTS13 activity ratio that was strongly associated with disease severity. Such an imbalance enhances the hypercoagulable state of COVID-19 patients and their risk of microthrombosis.
AB - Background: Severe coronavirus disease 2019 (COVID-19) is characterized by an increased risk of thromboembolic events, with evidence of microthrombosis in the lungs of deceased patients. Objectives: To investigate the mechanism of microthrombosis in COVID-19 progression. Patients/Methods: We assessed von Willebrand factor (VWF) antigen (VWF:Ag), VWF ristocetin-cofactor (VWF:RCo), VWF multimers, VWF propeptide (VWFpp), and ADAMTS13 activity in a cross-sectional study of 50 patients stratified according to their admission to three different intensity of care units: low (requiring high-flow nasal cannula oxygenation, n = 14), intermediate (requiring continuous positive airway pressure devices, n = 17), and high (requiring mechanical ventilation, n = 19). Results: Median VWF:Ag, VWF:RCo, and VWFpp levels were markedly elevated in COVID-19 patients and increased with intensity of care, with VWF:Ag being 268, 386, and 476 IU/dL; VWF:RCo 216, 334, and 388 IU/dL; and VWFpp 156, 172, and 192 IU/dL in patients at low, intermediate, and high intensity of care, respectively. Conversely, the high-to-low molecular-weight VWF multimers ratios progressively decreased with increasing intensity of care, as well as median ADAMTS13 activity levels, which ranged from 82 IU/dL for patients at low intensity of care to 62 and 55 IU/dL for those at intermediate and high intensity of care. Conclusions: We found a significant alteration of the VWF-ADAMTS13 axis in COVID-19 patients, with an elevated VWF:Ag to ADAMTS13 activity ratio that was strongly associated with disease severity. Such an imbalance enhances the hypercoagulable state of COVID-19 patients and their risk of microthrombosis.
KW - ADAMTS13 Protein
KW - COVID-19
KW - Microvasculature
KW - Severe acute respiratory syndrome coronavirus 2
KW - Thrombosis
KW - von Willebrand factor
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U2 - 10.1111/jth.15191
DO - 10.1111/jth.15191
M3 - Article
C2 - 33230904
AN - SCOPUS:85097797679
VL - 19
SP - 513
EP - 521
JO - Journal of Thrombosis and Haemostasis
JF - Journal of Thrombosis and Haemostasis
SN - 1538-7933
IS - 2
ER -