Schematic diagram illustrating the proposed mechanisms through which VWF is involved in malaria pathogenesis. EC activation and release of WP body contents constitute common early features in both human and murine malaria. This results in the secretion in the release of UL-VWF multimers into the plasma (1) and a marked increase in plasma VWF levels. VWF may influence malaria pathogenesis through several different mechanisms. First, UL-VWF strings on the surface of activated EC recruit and sequester platelets within the microvasculature (2). These tethered platelets cause further EC activation, and thus more WP body secretion. In addition, the platelet-decorated VWF may be important in modulating further sequestration by recruiting both malaria-infected erythrocytes and by binding to granulocytes and activated monocytes respectively (3). The VWF-mediated sequestration of platelets, infected erythrocytes, and leukocytes leads to further enhanced EC activation. During the later stages of CM pathogenesis, VWF may be important in regulating EC permeability, BBB permeability, and leukocyte extravasation (4). Finally, given that platelets play a critical role in the development of microvasculature occlusion, we postulate that VWF may also be important in this context (5).