TY - JOUR
T1 - ADAMTS13 deficiency with elevated levels of ultra-large and active von willebrand factor in P. falciparum and P. vivax malaria
AU - De Mast, Quirijn
AU - Groot, Evelyn
AU - Asih, Puji B.
AU - Syafruddin, Din
AU - Oosting, Marije
AU - Sebastian, Silvie
AU - Ferwerda, Bart
AU - Netea, Mihai G.
AU - De Groot, Philip G.
AU - Van Der Ven, Andre J.A.M.
AU - Fijnheer, Rob
PY - 2009/3
Y1 - 2009/3
N2 - A deficiency in ADAMTS13 (a von Willebrand factor [VWF] cleaving protease) is associated with accumulation of prothrombogenic unusually large VWF muitimers (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.
AB - A deficiency in ADAMTS13 (a von Willebrand factor [VWF] cleaving protease) is associated with accumulation of prothrombogenic unusually large VWF muitimers (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.
UR - http://www.scopus.com/inward/record.url?scp=62949125310&partnerID=8YFLogxK
U2 - https://doi.org/10.4269/ajtmh.2009.80.492
DO - https://doi.org/10.4269/ajtmh.2009.80.492
M3 - Article
C2 - 19270304
SN - 0002-9637
VL - 80
SP - 492
EP - 498
JO - American journal of tropical medicine and hygiene
JF - American journal of tropical medicine and hygiene
IS - 3
ER -