title: ADAMTS13 deficiency with elevated levels of ultra-large and active von Willebrand factor in P. falciparum and P. vivax malaria.
abstract: 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.
authors.affiliation: Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. q.demast@aig.umcn.nl
authors.forename: Quirijn
authors.initials: Q
authors.lastname: de Mast
authors.forename: Evelyn
authors.initials: E
authors.lastname: Groot
authors.forename: Puji B
authors.initials: PB
authors.lastname: Asih
authors.forename: Din
authors.initials: D
authors.lastname: Syafruddin
authors.forename: Marije
authors.initials: M
authors.lastname: Oosting
authors.forename: Silvie
authors.initials: S
authors.lastname: Sebastian
authors.forename: Bart
authors.initials: B
authors.lastname: Ferwerda
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Philip G
authors.initials: PG
authors.lastname: de Groot
authors.forename: Andre J A M
authors.initials: AJ
authors.lastname: van der Ven
authors.forename: Rob
authors.initials: R
authors.lastname: Fijnheer
mesh_terms: 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*
chemical_list: D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human