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COVID-19 is associated with relative ADAMTS13 deficiency and VWF multimer formation resembling TTP
Adrian A. N. Doevelaar; Martin Bachmann; Bodo Hoelzer; Felix S Seibert; Benjamin S Rohn; Frederic Bauer; Oliver Witzke; Ulf Dittmer; Michael Bachmann; Serap Yilmaz; Rita Dittmer; Sonja Schneppenheim; Nina Babel; Ulrich Budde; Timm H. Westhoff.
  • Adrian A. N. Doevelaar; Medical Department I, University Hospital Marien Hospital Herne, Ruhr-University Bochum, Bochum, Germany
  • Martin Bachmann; Intensive Care and Ventilatory Medicine, Asklepios Klinikum Hamburg Harburg, Hamburg, Germany
  • Bodo Hoelzer; Medical Department 1, University Hospital Marien Hospital Herne, Ruhr-University Bochum, Bochum, Germany
  • Felix S Seibert; Medical Department 1, University Hospital Marien Hospital Herne, Ruhr-University Bochum, Bochum, Germany
  • Benjamin S Rohn; Medical Department 1, University Hospital Marien Hospital Herne, Ruhr-University Bochum, Bochum, Germany
  • Frederic Bauer; Medical Department 1, University Hospital Marien Hospital Herne, Ruhr-University Bochum, Bochum, Germany
  • Oliver Witzke; Department of Infectiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
  • Ulf Dittmer; Department of Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
  • Michael Bachmann; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA
  • Serap Yilmaz; Intensive Care and Ventilatory Medicine, Asklepios Klinikum Hamburg Harburg, Hamburg, Germany
  • Rita Dittmer; Hemostaseology, MEDILYS Laborgesellschaft mbH, Hamburg, Germany
  • Sonja Schneppenheim; Hemostaseology, MEDILYS Laborgesellschaft mbH, Hamburg, Germany
  • Nina Babel; Center for Translational Medicine, University Hospital Marien Hospital Herne, Ruhr-University Bochum, Bochum, Germany
  • Ulrich Budde; Hemostaseology, MEDILYS Laborgesellschaft mbH, Hamburg, Germany
  • Timm H. Westhoff; Medical Department I, University Hospital Marien Hospital Herne, Ruhr-University Bochum, Bochum, Germany
Preprint in English | medRxiv | ID: ppmedrxiv-20177824
ABSTRACT
BackgroundThrombotic 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. MethodsA 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. ResultsVWFAg 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. ConclusionCOVID-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 Document Type: Preprint Language: English Year: 2020

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Full text: Available Collection: Preprints Database: medRxiv Document Type: Preprint Language: English Year: 2020
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