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.


OBJECTIVE
In order to elucidate the pathophysiological mechanism behind the development of thrombocytopenia, we studied the role of von Willebrand factor (VWF) in meningococcal disease.


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.
Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Utrecht, the Netherlands. J.Hollestelle@umcutrecht.nl
M J
MJ
Hollestelle
T
T
Sprong
N
N
Bovenschen
Q
Q
de Mast
A J
AJ
van der Ven
L A B
LA
Joosten
C
C
Neeleman
A
A
Hyseni
P J
PJ
Lenting
P G
PG
de Groot
M
M
van Deuren
D051722:ADAM Proteins / Q000378:metabolism; D000071120:ADAMTS13 Protein; D002648:Child; D002675:Child, Preschool; D005260:Female; D053804:Granzymes / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D016920:Meningitis, Bacterial / Q000150:complications / Q000201:enzymology / Q000378:metabolism*; D013921:Thrombocytopenia / Q000150:complications / Q000201:enzymology / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism*
D014841:von Willebrand Factor; D053804:Granzymes; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human