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Thromb Haemost 2010; 103(01): 181-187
DOI: 10.1160/TH09-04-0223
Wound Healing and Inflammation/Infection
Schattauer GmbH

Severe malaria is associated with a deficiency of von Willebrand factor cleaving protease, ADAMTS13

Ester C. Löwenberg
1   Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, the Netherlands
,
Prakaykaew Charunwatthana
2   Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
,
Sophie Cohen
1   Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, the Netherlands
,
Bert-Jan van den Born
1   Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, the Netherlands
,
Joost C. M. Meijers
1   Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, the Netherlands
,
Emran B. Yunus
3   Chittagong Medical College Hospital, Chittagong, Bangladesh
,
Mahtab B. Hassan
3   Chittagong Medical College Hospital, Chittagong, Bangladesh
,
Gofranul Hoque
3   Chittagong Medical College Hospital, Chittagong, Bangladesh
,
Richard J. Maude
2   Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
4   Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK
,
Forradee Nuchsongsin
2   Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
,
Marcel Levi
1   Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, the Netherlands
,
Arjen M. Dondorp
2   Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
4   Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK
› Author Affiliations
Further Information

Publication History

Received: 03 April 2009

Accepted after minor revision: 02 August 2009

Publication Date:
22 November 2017 (online)

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Summary

Severe falciparum malaria remains a major killer in tropical countries. Central in the pathophysiology is mechanical obstruction in the micro-circulation 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.

Keywords

ADAMTS13 - falciparum malaria - thrombotic microangiopathy - thrombotic thrombocytopenic purpura - von Willebrand factor cleaving pro-tease
 

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