title: Severe malaria is associated with a deficiency of von Willebrand factor cleaving protease, ADAMTS13.
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.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, the Netherlands. e.c.lowenberg@amc.uva.nl
authors.forename: Ester C
authors.initials: EC
authors.lastname: Löwenberg
authors.forename: Prakaykaew
authors.initials: P
authors.lastname: Charunwatthana
authors.forename: Sophie
authors.initials: S
authors.lastname: Cohen
authors.forename: Bert-Jan
authors.initials: BJ
authors.lastname: van den Born
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
authors.forename: Emran B
authors.initials: EB
authors.lastname: Yunus
authors.forename: Mahtab U
authors.initials: MU
authors.lastname: Hassan
authors.forename: Gofranul
authors.initials: G
authors.lastname: Hoque
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Maude
authors.forename: Forradee
authors.initials: F
authors.lastname: Nuchsongsin
authors.forename: Marcel
authors.initials: M
authors.lastname: Levi
authors.forename: Arjen M
authors.initials: AM
authors.lastname: Dondorp
mesh_terms: D051722:ADAM Proteins / Q000172:deficiency*; D000071120:ADAMTS13 Protein; D000328:Adult; D001459:Bangladesh; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016778:Malaria, Falciparum / Q000097:blood* / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D011498:Protein Precursors / Q000097:blood*; D012720:Severity of Illness Index; D015854:Up-Regulation; D055815:Young Adult; D014841:von Willebrand Factor
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; C508600:IL6 protein, human; D015850:Interleukin-6; D011498:Protein Precursors; D014841:von Willebrand Factor; C067003:von Willebrand factor propolypeptide; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human