['Platelets promote liver regeneration through site-specific serotonin release from dense granules, triggering proliferative signaling in hepatocytes. However, the effects of factors derived from platelet α-granules on liver regeneration are unclear, because α-granules contain bioactive molecules with opposing functions. Because α-granule molecules are stored in separate compartments, it has been suggested that platelets selectively release their α-granule content dependent on the environmental stimulus. Therefore, we investigated the pattern of circulating α-granule molecules during liver regeneration in 157 patients undergoing partial hepatectomy. We measured plasma levels of α-granule-derived factors in the liver vein at the end of liver resection, as well as on the first postoperative day. We observed a rapid accumulation of platelets within the liver after induction of liver regeneration. Platelet count and P-selectin (a ubiquitous cargo of α-granules) were not associated with postoperative liver dysfunction. However, low plasma levels of vascular endothelial growth factor (VEGF), but high levels of thrombospondin 1 (TSP-1), predicted liver dysfunction after resection. Patients with an unfavorable postoperative α-granule release profile (high TSP-1/low VEGF) showed substantially worse postoperative clinical outcomes. The unfavorable postoperative α-granule release profile was associated with increased postoperative portal venous pressure and von Willebrand factor antigen levels as a marker for intrahepatic endothelial dysfunction.'] Does the profile of platelet α-granule released molecules affect postoperative liver regeneration?