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, 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.
Löwenberg
Ester C
EC
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, the Netherlands. e.c.lowenberg@amc.uva.nl
Charunwatthana
Prakaykaew
P
Cohen
Sophie
S
van den Born
Bert-Jan
BJ
Meijers
Joost C M
JC
Yunus
Emran B
EB
Hassan
Mahtab U
MU
Hoque
Gofranul
G
Maude
Richard J
RJ
Nuchsongsin
Forradee
F
Levi
Marcel
M
Dondorp
Arjen M
AM
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
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