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Von Willebrand factor parameters as potential biomarkers for disease activity and coronary artery lesion in patients with Kawasaki disease

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European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Elevated von Willebrand factor (vWF):Antigen plasma levels have been observed in conjunction with cardiovascular diseases or vasculitis. The association of Kawasaki disease, a vascular inflammatory disease and vWF:Antigen, vWF:Collagen binding activity, and vWF multimers is unknown. We therefore investigated vWF parameters in 28 patients with acute Kawasaki disease in association with disease activity and coronary artery lesions. VWF:Antigen and vWF:Collagen binding activity were assessed via enzyme-linked immunoassay. The ratio of both (vWF:Collagen binding activity and VWF:Antigen) was calculated and vWF multimeric structure analysis performed. We analyzed the association between vWF parameters and our clinical data focusing on coronary artery outcome. VWF:Antigen and vWF:Collagen binding activity levels were significantly higher in the acute than in the disease’s convalescence phase, and correlated positively with CRP levels. Neither variable was associated with coronary artery lesions. The vWF:Collagen binding activity/vWF:Antigen ratio, however, was significantly decreased in patients with a coronary artery lesion (z-score > 2; N = 10; mean ratio 0.96 vs. 0.64; p = 0.031) and even more so in those with a coronary artery aneurysm (z-score > 2.5; N = 8; mean ratio 0.94 vs. 0.55; p = 0.02). In a sub-analysis, those patients with a very low ratio in the acute phase presented a persistent coronary artery aneurysm at their 1-year follow-up.

Conclusion: This study suggests that comprehensive analysis of vWF parameters may help to both monitor KD inflammation and facilitate the identification of those patients carrying an increased risk for coronary artery lesion.

What is Known:

• Von Willebrand factor (VWF)-parameters represent surrogate markers for vascular inflammation.

• Kawasaki disease is a generalized vasculitis in children, which can be complicated by coronary artery lesions.

What is New:

• In those Kawasaki disease patients with coronary artery lesions, the vWF:CB/vWF:Ag ratio was significantly decreased.

• VWF parameters may help to identify patients at risk for coronary artery lesions.

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Abbreviations

AHA:

American Heart Association

ALAT:

Alanine aminotransferase

ASAT:

Aspartate aminotransferase

CRP:

C-reactive protein

ELISA:

Enzyme-linked immunoassay

ESPED:

German Pediatric Surveillance Unit

ESR:

Erythrocyte sedimentation rate

Gamma GT:

Gamma-glutamyltransferase

IVIG :

Intravenous immunoglobulin

KD:

Kawasaki disease

PVDF:

Polyvinylidene difluoride

SD:

Standard deviation

TNFα:

Tumor necrosis factor α

vWF:

von Willebrand factor

vWF:Ag:

von Willebrand factor: antigen

vWF:CB:

von Willebrand factor: collagen binding

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Funding

André Jakob received funding for this work by a grant from the German Heart Foundation.

Author information

Authors and Affiliations

  1. Department of Pediatric Cardiology and Pediatric Intensive Care, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany

    André Jakob, Anja Lehner & Sarah Ulrich

  2. Department of Congenital Heart Defects and Pediatric Cardiology, Heart Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

    Eva Schachinger & Brigitte Stiller

  3. Institute for Medical Information Processing, Biometry and Epidemiology, Ludwig-Maximilians-University of Munich, Munich, Germany

    Simon Klau

  4. Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

    Barbara Zieger

Authors
  1. André Jakob
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  2. Eva Schachinger
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  3. Simon Klau
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  4. Anja Lehner
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  5. Sarah Ulrich
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  6. Brigitte Stiller
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  7. Barbara Zieger
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Contributions

André Jakob: Conceived and designed the study, contributed to statistical analyses and data interpretation, drafted the manuscript and approved the final manuscript as submitted.

Eva Schachinger: Responsible for data collection, contributed to statistical analysis and study design, as well as approved the final manuscript as submitted.

Simon Klau: Conducted the statistical analysis, contributed to drafting the manuscript and approved the final manuscript as submitted.

Anja Lehner, Sarah Ulrich and Brigitte Stiller: Contributed to data interpretation, served on the adjudicating committee and approved the final manuscript as submitted.

Barbara Zieger: Contributed to the study design, data interpretation and statistical analysis. She is responsible for the VWF analyses and contributed to drafting the manuscript; she has approved the final manuscript as submitted.

Corresponding author

Correspondence to André Jakob.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Approval for our study had been provided by the Ethics Committee of the University of Freiburg, in accordance with Declaration of Helsinki ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in this study.

Additional information

Communicated by Peter de Winter

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Clinical Trial Registration: German clinical trial registration, DRKS00010071 http://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00010071

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Jakob, A., Schachinger, E., Klau, S. et al. Von Willebrand factor parameters as potential biomarkers for disease activity and coronary artery lesion in patients with Kawasaki disease. Eur J Pediatr 179, 377–384 (2020). https://doi.org/10.1007/s00431-019-03513-6

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  • DOI: https://doi.org/10.1007/s00431-019-03513-6

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