Abstract
Background and Aim: Blood platelets have been shown to stimulate liver regeneration after partial hepatectomy in animal models and humans, but the molecular mechanisms involved are unclear. It has been proposed that growth factors and angiogenic molecules stored within platelets drive platelet-mediated liver regeneration, but little direct evidence in support of this mechanism is available. Methods: We assessed levels of relevant platelet-derived proteins (vascular endothelial growth factor, hepatocyte growth factor, fibroblast growth factor, platelet-derived growth factor, thrombospondin, and endostatin) in platelet-rich and platelet-poor plasma taken at various perioperative time points from patients undergoing a (extended) right partial hepatectomy (n = 17) or a pylorus-preserving pancreatico-duodenectomy (n = 10). In addition, we collected intraoperative samples from the efferent and afferent liver veins prior to and after completion of liver resection. Twenty-four healthy controls were included to establish reference ranges for the various tests. Results and Conclusions: Although we demonstrate perioperative changes in platelet and plasma levels of the proteins assessed, the changes observed in patients undergoing partial hepatectomy largely mirror the changes observed in patients undergoing a pylorus-preserving pancreatico-duodenectomy. In addition, no change in the growth factor levels in platelet-rich plasma between afferent and efferent liver veins was observed. Thus, the absence of an intra- or postoperative consumption of platelet-derived proteins in patients undergoing partial hepatectomy argues against a role of release of these molecules in stimulation of liver regeneration. Relevance for patients: In depth knowledge of the mechanism underlying platelet-mediated liver regeneration may facilitate development of targeted therapeutic interventions for patients with failing liver regeneration, which for example may occur following a partial hepatectomy. Although the prevailing dogma is that platelet stimulate liver regeneration by release of growth factors stored within platelets, data in this manuscript argue against this mechanism and suggest other pathways to be responsible.
Highlights
Platelets are well known for their functions in thrombosis and hemostasis
We assessed levels of relevant platelet-derived proteins in platelet-rich and platelet-poor plasma taken at various perioperative time points from patients undergoing a right partial hepatectomy (n = 17) or a pylorus-preserving pancreatico-duodenectomy (n = 10)
Seventeen patients who underwent a right (n = 15) or extended right (n = 2) partial hepatectomy, 10 patients who underwent a pylorus-preserving pancreatico-duodenectomy (PPPD), and twenty-four controls were included in the study
Summary
Platelets are well known for their functions in thrombosis and hemostasis. In addition, platelets have roles beyond physiological or pathological thrombus formation [1,2,3]. Some studies suggest that local release of growth factors or angiogenic molecules stored within platelet alpha and dense granules are responsible for platelet-mediated liver regeneration [4,13,14,15,16]. Blood platelets have been shown to stimulate liver regeneration after partial hepatectomy in animal models and humans, but the molecular mechanisms involved are unclear. Results and Conclusions: we demonstrate perioperative changes in platelet and plasma levels of the proteins assessed, the changes observed in patients undergoing partial hepatectomy largely mirror the changes observed in patients undergoing a pylorus-preserving pancreatico-duodenectomy. The absence of an intra- or postoperative consumption of platelet-derived proteins in patients undergoing partial hepatectomy argues against a role of release of these molecules in stimulation of liver regeneration. The prevailing dogma is that platelet stimulate liver regeneration by release of growth factors stored within platelets, data in this manuscript argue against this mechanism and suggest other pathways to be responsible
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