ADAMTS13 deficiency with elevated levels of ultra-large and active von Willebrand factor in P. falciparum and P. vivax malaria.
A deficiency in ADAMTS13 (a von Willebrand factor [VWF] cleaving protease) is associated with accumulation of prothrombogenic unusually large VWF multimers (UL-VWF) in plasma. We studied VWF release and proteolysis in patients with symptomatic Plasmodium falciparum or P. vivax malaria on the Indonesian island Sumba. Malaria patients had significantly lower platelet counts and higher VWF concentrations and VWF activation factors than healthy hospital staff controls. The latter indicates that a higher amount of circulating VWF was in a conformation enabling spontaneous platelet binding. In addition, ADAMTS13 activity and antigen levels were reduced in both malaria groups, and this was associated with the appearance of UL-VWF. The mechanism behind this reduction and the role in malaria pathogenesis needs to be further elucidated. In malaria, endothelial cell activation with increased circulating amounts of active and ultra-large VWF, together with reduced VWF inactivation by ADAMTS13, may result in intravascular platelet aggregation, thrombocytopenia, and microvascular disease.
de Mast
Quirijn
Q
Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. q.demast@aig.umcn.nl
Groot
Evelyn
E
Asih
Puji B
PB
Syafruddin
Din
D
Oosting
Marije
M
Sebastian
Silvie
S
Ferwerda
Bart
B
Netea
Mihai G
MG
de Groot
Philip G
PG
van der Ven
Andre J A M
AJ
Fijnheer
Rob
R
D051722:ADAM Proteins / Q000172:deficiency / Q000235:genetics*; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007214:Indonesia / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D016780:Malaria, Vivax / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009154:Mutation; D010963:Plasmodium falciparum; D010966:Plasmodium vivax; D055815:Young Adult; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism*
D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human