Thrombocytopenia and release of activated von Willebrand Factor during early Plasmodium falciparum malaria.
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.
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
Lenting
Peter J
PJ
de Groot
Philip G
PG
McCall
Matthew
M
Sauerwein
Robert W
RW
Fijnheer
Rob
R
van der Ven
Andre
A
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*
D014841:von Willebrand Factor