von Willebrand factor activation, granzyme‐B and thrombocytopenia in meningococcal disease

Background: During invasive meningococcal disease, severe thrombocytopenia is strongly associated with a poor outcome. Objectives: In order to elucidate the pathophysiological mechanism behind the development of thrombocytopenia, we studied the role of von Willebrand factor (VWF) in meningococcal di...

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Published in:Journal of thrombosis and haemostasis 2010-05, Vol.8 (5), p.1098-1106
Main Authors: HOLLESTELLE, M. J., SPRONG, T., BOVENSCHEN, N., De MAST, Q., Van Der VEN, A. J., JOOSTEN, L. A. B., NEELEMAN, C., HYSENI, A., LENTING, P. J., De GROOT, P. G., Van DEUREN, M.
Format: Article
Language:English
Subjects:
ADAM Proteins - metabolism
ADAMTS13 Protein
Child
Child, Preschool
Children
Endothelial cells
Female
granzyme B
Granzymes - metabolism
Hospitals
Humans
Infant
Invasive meningococcal disease
Male
Meningitis, Bacterial - complications
Meningitis, Bacterial - enzymology
Meningitis, Bacterial - metabolism
meningococcal disease
Neisseria meningitidis
sepsis
Shock
Thrombocytopenia
Thrombocytopenia - complications
Thrombocytopenia - enzymology
Thrombocytopenia - metabolism
Thrombosis
Von Willebrand factor
von Willebrand Factor - metabolism
VWF
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Summary:Background: During invasive meningococcal disease, severe thrombocytopenia is strongly associated with a poor outcome. Objectives: In order to elucidate the pathophysiological mechanism behind the development of thrombocytopenia, we studied the role of von Willebrand factor (VWF) in meningococcal disease. Patients/methods: Thirty‐two children with severe meningococcal disease admitted to our university hospital were included in this study. VWF and related parameters were measured and results were correlated with the development of shock and thrombocytopenia. Results: At admission, all patients had increased levels of (active) VWF and VWF propeptide. The highest VWF propeptide levels were observed in patients with shock, indicating acute endothelial activation. Although VWF propeptide levels in patients with shock, with or without thrombocytopenia, were similar, increased active VWF was significantly lower in patients with thrombocytopenia as compared with patients without thrombocytopenia. ADAMTS13 was moderately decreased. However, the VWF multimeric pattern was minimally increased. We assume that these findings are explained by VWF consumption and perhaps by granzyme B (GrB). In vitro experiments showed that GrB is able to cleave VWF multimers in plasma, whereas GrB was high in patients with shock, who developed thrombocytopenia. Conclusions: Our results demonstrate that consumption of VWF, derived from endothelial cells, could be a key feature of meningococcal disease and primary to the development of thrombocytopenia during shock.
ISSN:1538-7933
1538-7836
1538-7836
DOI:10.1111/j.1538-7836.2010.03811.x