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

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, incl...

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Main Authors: Löwenberg, E, Charunwatthana, P, Cohen, S, van den Born, B, Meijers, J, Yunus, E, Hassan, M, Hoque, G, Maude, R, Nuchsongsin, F, Levi, M, Dondorp, A
Format: Journal article
Language:English
Published: 2010
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author Löwenberg, E
Charunwatthana, P
Cohen, S
van den Born, B
Meijers, J
Yunus, E
Hassan, M
Hoque, G
Maude, R
Nuchsongsin, F
Levi, M
Dondorp, A
author_facet Löwenberg, E
Charunwatthana, P
Cohen, S
van den Born, B
Meijers, J
Yunus, E
Hassan, M
Hoque, G
Maude, R
Nuchsongsin, F
Levi, M
Dondorp, A
author_sort Löwenberg, E
collection OXFORD
description 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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spelling oxford-uuid:65f4abf8-719b-4970-bde0-64cd7fabc84e2022-03-26T18:28:53ZSevere malaria is associated with a deficiency of von Willebrand factor cleaving protease, ADAMTS13.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:65f4abf8-719b-4970-bde0-64cd7fabc84eEnglishSymplectic Elements at Oxford2010Löwenberg, ECharunwatthana, PCohen, Svan den Born, BMeijers, JYunus, EHassan, MHoque, GMaude, RNuchsongsin, FLevi, MDondorp, ASevere 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.
spellingShingle Löwenberg, E
Charunwatthana, P
Cohen, S
van den Born, B
Meijers, J
Yunus, E
Hassan, M
Hoque, G
Maude, R
Nuchsongsin, F
Levi, M
Dondorp, A
Severe malaria is associated with a deficiency of von Willebrand factor cleaving protease, ADAMTS13.
title Severe malaria is associated with a deficiency of von Willebrand factor cleaving protease, ADAMTS13.
title_full Severe malaria is associated with a deficiency of von Willebrand factor cleaving protease, ADAMTS13.
title_fullStr Severe malaria is associated with a deficiency of von Willebrand factor cleaving protease, ADAMTS13.
title_full_unstemmed Severe malaria is associated with a deficiency of von Willebrand factor cleaving protease, ADAMTS13.
title_short Severe malaria is associated with a deficiency of von Willebrand factor cleaving protease, ADAMTS13.
title_sort severe malaria is associated with a deficiency of von willebrand factor cleaving protease adamts13
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