von Willebrand factor increases in experimental cerebral malaria but is not essential for late-stage pathogenesis in mice.

Background: Cerebral malaria (CM) is the most severe complication of malaria. Endothelial activation, cytokine release, and vascular obstruction are essential hallmarks of CM. Clinical studies have suggested a link between von Willebrand factor (VWF) and malaria pathology.
Objectives: To investigate the contribution of VWF in the pathogenesis of experimental cerebral malaria (ECM).
Methods: Both Vwf ^+/+ and Vwf ^-/- mice were infected with Plasmodium berghei ANKA (PbANKA) to induce ECM. Alterations of plasma VWF and ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), platelet count, neurological features, and accumulation of platelets and leukocytes in the brain were examined following infection.
Results: Plasma VWF levels significantly increased upon PbANKA infection in Vwf ^+/+ animals. While ADAMTS13 activity was not affected, high molecular weight VWF multimers disappeared at the end-stage ECM, possibly due to an ongoing hypercoagulability. Although the number of reticulocytes, a preferential target for the parasites, was increased in Vwf ^-/- mice compared to Vwf ^+/+ mice early after infection, parasitemia levels did not markedly differ between the two groups. Interestingly, Vwf ^-/- mice manifested overall clinical ECM features similar to those observed in Vwf ^+/+ animals. At day 8.5 post-infection, however, clinical ECM features in Vwf ^-/- mice were slightly more beneficial than in Vwf ^+/+ animals. Despite these minor differences, overall survival was not different between Vwf ^-/- and Vwf ^+/+ mice. Similarly, PbANKA-induced thrombocytopenia, leukocyte, and platelet accumulations in the brain were not altered by the absence of VWF.
Conclusions: Our study suggests that increased VWF concentration is a hallmark of ECM. However, VWF does not have a major influence in modulating late-stage ECM pathogenesis.
(© 2020 International Society on Thrombosis and Haemostasis.)