VWF-deficient mice are significantly protected against ECM. To investigate whether VWF may be directly involved in the pathogenesis of ECM, P berghei infection in VWF^−/− mice was investigated. (A) Following inoculation with P berghei, clinical phenotype and progression in VWF^−/− mice (n = 10) and WT C57BL/6J mice (n = 16) were compared using a validated clinical scoring algorithm. Results presented represent the mean values ± SEM (*P < .05, **P < .01, ***P < .0001, respectively). (B) In addition, overall survival in WT (n = 16) and VWF^−/− (n = 10) mice infected with 2 × 10⁶P berghei parasites was also determined and analyzed by log-rank (Mantel-Cox) test. (C) Because VWF plays a critical role in modulating platelet adhesion and aggregation, sequential platelet counts were performed in VWF^−/− mice and WT C57BL/6J mice following P berghei infection (n = 4-5 mice per time point). (D) Peripheral blood P berghei parasitemia levels were determined following inoculation in both VWF^−/− (n = 10) and WT C57BL/6J mice (n = 10) at specified time points from Giemsa-stained smears. Results presented represent the mean values ± SEM.