Document Detail


Severe malaria is associated with a deficiency of von Willebrand factor cleaving protease, ADAMTS13.
MedLine Citation:
PMID:  20062916     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Severe falciparum malaria remains a major killer in tropical countries. Central in the pathophysiology is mechanical obstruction in the microcirculation caused by cytoadherence and sequestration of parasitized erythrocytes. However, the pathogenesis of many features complicating severe malaria, including coma, renal failure and thrombocytopenia, remains incompletely understood. These disease manifestations are also key features of thrombotic thrombocytopenic purpura, a life-threatening disease strongly associated with a deficiency of the von Willebrand factor (VWF) cleaving protease, ADAMTS13. We measured plasma ADAMTS13 activity, VWF antigen and VWF propeptide levels in 30 patients with severe falciparum malaria, 12 patients with uncomplicated falciparum malaria and 14 healthy Bangladeshi controls. In patients with severe malaria ADAMTS13 activity levels were markedly decreased in comparison to normal controls (mean [95%CI]: 23% [20-26] vs. 64% [55-72]) and VWF antigen and propeptide concentrations were significantly elevated (VWF antigen: 439% [396-481] vs. 64% [46-83]; VWF propeptide: 576% [481-671] vs. 69% [59-78]). In uncomplicated malaria VWF levels were also increased compared to healthy controls but ADAMTS13 activity was normal. The results suggest that decreased ADAMTS13 activity in combination with increased VWF concentrations may contribute to the complications in severe malaria.
Authors:
Ester C L?wenberg; Prakaykaew Charunwatthana; Sophie Cohen; Bert-Jan van den Born; Joost C M Meijers; Emran B Yunus; Mahtab U Hassan; Gofranul Hoque; Richard J Maude; Forradee Nuchsongsin; Marcel Levi; Arjen M Dondorp
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-15
Journal Detail:
Title:  Thrombosis and haemostasis     Volume:  103     ISSN:  0340-6245     ISO Abbreviation:  Thromb. Haemost.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-11     Completed Date:  2010-03-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7608063     Medline TA:  Thromb Haemost     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  181-7     Citation Subset:  IM    
Affiliation:
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, the Netherlands. e.c.lowenberg@amc.uva.nl
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MeSH Terms
Descriptor/Qualifier:
ADAM Proteins / deficiency*
Adult
Bangladesh
Biological Markers / blood
Blood Coagulation*
Case-Control Studies
Down-Regulation
Female
Hemoglobins / metabolism
Humans
Interleukin-6 / blood
Malaria, Falciparum / blood*,  enzymology*
Male
Middle Aged
Protein Precursors / blood*
Severity of Illness Index
Up-Regulation
Young Adult
von Willebrand Factor
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Hemoglobins; 0/IL6 protein, human; 0/Interleukin-6; 0/Protein Precursors; 0/von Willebrand Factor; 0/von Willebrand factor propolypeptide; EC 3.4.24.-/ADAM Proteins; EC 3.4.24.-/ADAMTS13 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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