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COVID-19 is associated with relative ADAMTS13 deficiency and VWF multimer formation resembling TTP (preprint)
medrxiv; 2020.
Preprint
in English
| medRxiv | ID: ppzbmed-10.1101.2020.08.23.20177824
ABSTRACT
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 (VWFAg), ADAMTS13 and VWF multimer formation were analyzed in a German hemostaseologic laboratory.Results:
VWFAg 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/VWFAg 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/VWFAg 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/VWFAg 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.
Full text:
Available
Collection:
Preprints
Database:
medRxiv
Main subject:
Purpura, Thrombotic Thrombocytopenic
/
Von Willebrand Diseases
/
Thrombophilia
/
Thrombotic Microangiopathies
/
COVID-19
Language:
English
Year:
2020
Document Type:
Preprint
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