COVID-19 is associated with relative ADAMTS13 deficiency and VWF multimer formation resembling TTP Article Swipe
Adrian Doevelaar
,
Martin Bachmann
,
Bodo Hölzer
,
Felix S. Seibert
,
Benjamin S. Rohn
,
Frederic Bauer
,
Oliver Witzke
,
Ulf Dittmer
,
Michael H. Bachmann
,
Serap Yılmaz
,
Rita Dittmer
,
Sonja Schneppenheim
,
Nina Babel
,
Ulrich Budde
,
Timm H. Westhoff
·
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.1101/2020.08.23.20177824
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.1101/2020.08.23.20177824
Background Thrombotic microangiopathy (TMA) has been repeatedly described in COVID-19 and may contribute to SARS-CoV-2 associated hypercoagulability. The underlying mechanisms remain elusive. We hypothesized that endothelial damage may lead to substantially increased concentrations of Von Willebrand Factor (VWF) with subsequent relative deficiency of ADAMTS13. Methods A prospective controlled trial was performed on 75 patients with COVID-19 of mild to critical severity and 10 healthy controls. VWF antigen (VWF:Ag), ADAMTS13 and VWF multimer formation were analyzed in a German hemostaseologic laboratory. Results VWF:Ag was 4.8 times higher in COVID-19 patients compared to healthy controls (p< 0.0001), whereas ADAMTS13 activities were not significantly different (p = 0.24). The ADAMTS13/VWF:Ag ratio was significantly lower in COVID-19 than in the control group (24.4±20.5 vs. 79.7±33.2, p< 0.0001). Fourteen patients (18.7%) undercut a critical ratio of 10 as described in thrombotic thrombocytopenic purpura (TTP). Gel analysis of multimers resembled the TTP constellation with loss of the largest multimers in 75% and a smeary triplet pattern in 39% of the patients. The ADAMTS13/VWF:Ag ratio decreased continuously from mild to critical disease (ANOVA p = 0.026). Moreover, it differed significantly between surviving patients and those who died from COVID-19 (p = 0.001) yielding an AUC of 0.232 in ROC curve analysis. Conclusion COVID-19 is associated with a substantial increase in VWF levels, which can exceed the ADAMTS13 processing capacity resulting in the formation of large VWF multimers identical to TTP. The ADAMTS13/VWF:Ag ratio is an independent predictor of severity of disease and mortality. These findings render further support to perform studies on the use of plasma exchange in COVID-19 and to include VWF and ADAMTS13 in the diagnostic workup.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2020.08.23.20177824
- https://www.medrxiv.org/content/medrxiv/early/2020/08/25/2020.08.23.20177824.full.pdf
- OA Status
- green
- Cited By
- 11
- References
- 28
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3081046432
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3081046432Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1101/2020.08.23.20177824Digital Object Identifier
- Title
-
COVID-19 is associated with relative ADAMTS13 deficiency and VWF multimer formation resembling TTPWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2020Year of publication
- Publication date
-
2020-08-25Full publication date if available
- Authors
-
Adrian Doevelaar, Martin Bachmann, Bodo Hölzer, Felix S. Seibert, Benjamin S. Rohn, Frederic Bauer, Oliver Witzke, Ulf Dittmer, Michael H. Bachmann, Serap Yılmaz, Rita Dittmer, Sonja Schneppenheim, Nina Babel, Ulrich Budde, Timm H. WesthoffList of authors in order
- Landing page
-
https://doi.org/10.1101/2020.08.23.20177824Publisher landing page
- PDF URL
-
https://www.medrxiv.org/content/medrxiv/early/2020/08/25/2020.08.23.20177824.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.medrxiv.org/content/medrxiv/early/2020/08/25/2020.08.23.20177824.full.pdfDirect OA link when available
- Concepts
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ADAMTS13, Von Willebrand factor, Thrombotic thrombocytopenic purpura, Thrombotic microangiopathy, Coronavirus disease 2019 (COVID-19), Internal medicine, Gastroenterology, Medicine, Microangiopathy, Immunology, Platelet, Endocrinology, Disease, Diabetes mellitus, Infectious disease (medical specialty)Top concepts (fields/topics) attached by OpenAlex
- Cited by
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11Total citation count in OpenAlex
- Citations by year (recent)
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2023: 3, 2022: 2, 2021: 3, 2020: 3Per-year citation counts (last 5 years)
- References (count)
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28Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.microangiopathy | 3 |
| abstract_inverted_index.thrombocytopenic | 137 |
| abstract_inverted_index.hypercoagulability. | 17 |
| cited_by_percentile_year.max | 97 |
| cited_by_percentile_year.min | 94 |
| corresponding_author_ids | https://openalex.org/A5048155216 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 15 |
| corresponding_institution_ids | https://openalex.org/I4210088550, https://openalex.org/I904495901 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.8299999833106995 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.7390384 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |