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

Ester C. Löwenberg; Prakaykaew Charunwatthana; Sophie Cohen; Bert-Jan van den Born; Joost C. M. Meijers; Emran B. Yunus; Mahtab B. Hassan; Gofranul Hoque; Richard J. Maude; Forradee Nuchsongsin; Marcel Levi; Arjen M. Dondorp

doi:10.1160/TH09-04-0223

Thrombosis and Haemostasis, Table of Contents

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

Authors

Ester C. Löwenberg

¹Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, the Netherlands
Prakaykaew Charunwatthana

²Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Sophie Cohen

¹Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, the Netherlands
Bert-Jan van den Born

¹Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, the Netherlands
Joost C. M. Meijers

¹Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, the Netherlands
Emran B. Yunus

³Chittagong Medical College Hospital, Chittagong, Bangladesh
Mahtab B. Hassan

³Chittagong Medical College Hospital, Chittagong, Bangladesh
Gofranul Hoque

³Chittagong Medical College Hospital, Chittagong, Bangladesh
Richard J. Maude

²Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

⁴Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK
Forradee Nuchsongsin

²Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Marcel Levi

¹Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, the Netherlands
Arjen M. Dondorp

²Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

⁴Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK

Abstract

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

Full Text

References

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