Schematic representation of 3 different modes of regulated exocytosis described for WPBs. (A) “Conventional” exocytosis in which single WPBs fuse with the plasma membrane, thereby releasing their cargo. For simplicity, the release of only 2 different cargo molecules is depicted: membrane-bound P-selectin released into the plasma membrane, and VWF released into the blood, where it can form long strings. The content of multiple exocytosed WPBs may contribute to the formation of VWF strings. Binding of the VWF strings to platelets, collagen, and integrin α_vβ₃ is not shown. (B) Lingering-kiss exocytosis is shown, where single WPBs fuse with the plasma membrane via a small fusion pore of approximately 12 nm in diameter.⁸⁰  Because of the small size of the fusion pore, larger cargo proteins such as P-selectin and VWF are retained, whereas the smaller membrane-bound CD63 and soluble IL-8 are released. Lingering-kiss exocytosis of WPBs is characterized by the rounding up of the WPBs. The partially emptied and rounded WPBs are presumed to retract from the plasma membrane, but their fate is unknown. (C, D) Multigranular exocytosis where before exocytosis, WPBs coalesce into large intracellular membrane vesicles, termed secretory pods. As depicted in panel C, the coalescence of WPBs into secretory pods is mediated by interposing tiny vesicles termed nanovesicles.⁸⁵  Within the secretory pods, VWF loses its characteristic tubular organization. Clathrin-coated profiles on the secretory pods suggest remodeling via a clathrin-mediated pathway. As illustrated in panel D, secretory pods fuse with the plasma membrane and release VWF strings via a large pore with a diameter of 1-2 μm. Whether P-selectin and other cargo molecules are released or selectively retained during multigranular exocytosis, remains to be established.