Details of the sites of synthesis and clearance of VWF and FVIII. Although the synthesis of VWF has long been known to be the vascular endothelium and megakaryocytes, the location of FVIII expression has only recently been confirmed in some types of endothelial cell: in fenestrated forms of endothelium (liver sinusoidal endothelium and glomerular endothelium), in lymphatic endothelium, and in some high endothelial venules. In most forms of endothelium, VWF and FVIII are not coexpressed. Clearance of VWF and FVIII occurs most frequently as a complex, in the sinusoids of the liver and spleen where a range of lectin and scavenger receptors expressed on macrophages, sinusoidal endothelium, and hepatocytes bind to and internalize the 2 proteins. Protein clearance is influenced by factors such as shear, desialylation, and protein sequence variants. SCARA5, scavenger receptor class A, member 5.