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

Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, the Netherlands.
Thrombosis and Haemostasis (Impact Factor: 6.09). 01/2010; 103(1):181-7. DOI:10.1160/TH09-04-0223
Source: PubMed

ABSTRACT 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.

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    ABSTRACT: Malaria is a disease that causes enormous human morbidity and mortality. One feature of mature Plasmodium falciparum-infected erythrocytes leading to the development of severe malaria is thought to be cytoadherence and blockage of the microvasculature. Therefore, an understanding of mechanisms that mediate parasite adhesion leading to malaria pathology is needed to yield new treatments for malaria. However, to date, cytoadherence-associated pathology is still under debate. Is cytoadherence needed to develop severe malaria? This review will discuss the available information on associations of cytoadherence with the development of severe malaria.
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