title: Thrombocytopenia and release of activated von Willebrand Factor during early Plasmodium falciparum malaria.
abstract: BACKGROUND
  Thrombocytopenia occurs early during malarial infection, but its underlying mechanism is unclear. Secretion of von Willebrand factor (vWF) occurs on endothelial cell activation, and it plays an important role in platelet agglutination.
  
  
  METHODS
  In 14 healthy human volunteers who were experimentally infected with Plasmodium falciparum, we studied vWF secretion and proteolysis as well as the relationship between changes in circulating platelet numbers and plasma levels of vWF and activated vWF.
  
  
  RESULTS
  Platelet numbers started to decrease between days 7 and 9 after infection, which corresponded to the earliest phase of blood-stage infection. With the decrease in platelet numbers, levels of vWF, vWF propeptide (markers of chronic and acute endothelial cell activation, respectively), and activated vWF (exposing the glycoprotein Ib alpha platelet-binding domain) increased proportionally. A strong, reciprocal relationship was observed between platelet numbers and levels of both vWF and activated vWF. Activity of the vWF-cleaving protease ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) -- a regulator of vWF activity -- remained unchanged.
  
  
  CONCLUSIONS
  P. falciparum induces systemic acute endothelial cell activation and release of activated vWF immediately after the onset of blood-stage infection. The resulting platelet agglutination may result in early thrombocytopenia and may play a role in the pathogenesis of malaria.
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: Peter J
authors.initials: PJ
authors.lastname: Lenting
authors.forename: Philip G
authors.initials: PG
authors.lastname: de Groot
authors.forename: Matthew
authors.initials: M
authors.lastname: McCall
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.forename: Rob
authors.initials: R
authors.lastname: Fijnheer
authors.forename: Andre
authors.initials: A
authors.lastname: van der Ven
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000276:immunology; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood* / Q000150:complications*; D010963:Plasmodium falciparum; D010976:Platelet Count; D013921:Thrombocytopenia / Q000209:etiology*; D013997:Time Factors; D014841:von Willebrand Factor / Q000032:analysis*
chemical_list: D014841:von Willebrand Factor