The University of Dublin | Trinity College -- Ollscoil Átha Cliath | Coláiste na Tríonóide
Trinity's Access to Research Archive
Home :: Log In :: Submit :: Alerts ::

TARA >
School of Medicine >
Haematology >
Haematology (Scholarly Publications) >

Please use this identifier to cite or link to this item: http://hdl.handle.net/2262/40162

Title: Severe Plasmodium falciparum malaria is associated with circulating ultra-large von Willebrand multimers and ADAMTS13 inhibition.
Author: JENKINS, P VINCENT
O'DONNELL, JAMES
PRESTON, ROGER
Sponsor: Science Foundation Ireland
Author's Homepage: http://people.tcd.ie/prestonr
http://people.tcd.ie/jenkinsp
http://people.tcd.ie/jodonne
Keywords: Infectious Diseases
malaria
Issue Date: 2009
Publisher: PLoS
Citation: Larkin, D, de Laat, B, Jenkins, PV, Bunn, J, Craig, AG, Terraube, V, Preston, RJ, Donkor, C, Grau, GE, van Mourik, JA, O'Donnell, JS, Severe Plasmodium falciparum malaria is associated with circulating ultra-large von Willebrand multimers and ADAMTS13 inhibition., PLoS Pathogens, 5, 3, 2009, 1 - 8
Series/Report no.: PLoS Pathogens;
5;
3;
Abstract: Plasmodium falciparum infection results in adhesion of infected erythrocytes to blood vessel endothelium, and acute endothelial cell activation, together with sequestration of platelets and leucocytes. We have previously shown that patients with severe infection or fulminant cerebral malaria have significantly increased circulatory levels of the adhesive glycoprotein von Willebrand factor (VWF) and its propeptide, both of which are indices of endothelial cell activation. In this prospective study of patients from Ghana with severe (n = 20) and cerebral (n = 13) P. falciparum malaria, we demonstrate that increased plasma VWF antigen (VWF:Ag) level is associated with disproportionately increased VWF function. VWF collagen binding (VWF:CB) was significantly increased in patients with cerebral malaria and severe malaria (medians 7.6 and 7.0 IU/ml versus 1.9 IU/ml; p<0.005). This increased VWF:CB correlated with the presence of abnormal ultra-large VWF multimers in patient rather than control plasmas. Concomitant with the increase in VWF:Ag and VWF:CB was a significant persistent reduction in the activity of the VWF-specific cleaving protease ADAMTS13 (approximately 55% of normal; p<0.005). Mixing studies were performed using P. falciparum patient plasma and normal pooled plasma, in the presence or absence of exogenous recombinant ADAMTS13. These studies demonstrated that in malarial plasma, ADAMTS13 function was persistently inhibited in a time-dependent manner. Furthermore, this inhibitory effect was not associated with the presence of known inhibitors of ADAMTS13 enzymatic function (interleukin-6, free haemoglobin, factor VIII or thrombospondin-1). These novel findings suggest that severe P. falciparum infection is associated with acute endothelial cell activation, abnormal circulating ULVWF multimers, and a significant reduction in plasma ADAMTS13 function which is mediated at least in part by an unidentified inhibitor.
Description: PUBLISHED
URI: http://hdl.handle.net/2262/40162
Related links: http://dx.doi.org/10.1371/journal.ppat.1000349
Appears in Collections:Haematology (Scholarly Publications)

Files in This Item:

File Description SizeFormat
Severe Plasmodium falciparum malaria is associated with circulating ultra-large von Willebrand multimers and ADAMTS13 inhibition.xmlPublished (publisher's copy) - Peer Reviewed85.16 kBXMLView/Open
Severe Plasmodium falciparum Malaria Is Associated with Circulating Ultra-Large von Willebrand Multimers and ADAMTS13 Inhibition.pdfPublished (publisher's copy) - Peer Reviewed341.12 kBAdobe PDFView/Open


This item is protected by original copyright


Please note: There is a known bug in some browsers that causes an error when a user tries to view large pdf file within the browser window. If you receive the message "The file is damaged and could not be repaired", please try one of the solutions linked below based on the browser you are using.

Items in TARA are protected by copyright, with all rights reserved, unless otherwise indicated.

 

Valid XHTML 1.0! DSpace Software Copyright © 2002-2010  Duraspace - Feedback