Dualistic role of platelets in living donor liver transplantation: Are they harmful?

Abstract

Platelets are anucleate fragments mainly involved in hemostasis and thrombosis, and there is emerging evidence that platelets have other nonhemostatic potentials in inflammation, angiogenesis, regeneration and ischemia/reperfusion injury (I/R injury), which are involved in the physiological and pathological processes during living donor liver transplantation (LDLT). LDLT is sometimes associated with impaired regeneration and severe I/R injury, leading to postoperative complications and decreased patient survival. Recent studies have suggested that perioperative thrombocytopenia is associated with poor graft regeneration and postoperative morbidity in the short and long term after LDLT. Although it is not fully understood whether thrombocytopenia is the cause or result, increasing platelet counts are frequently suggested to improve posttransplant outcomes in clinical studies. Based on rodent experiments, previous studies have identified that platelets stimulate liver regeneration after partial hepatectomy. However, the role of platelets in LDLT is controversial, as platelets are supposed to aggravate I/R injury in the liver. Recently, a rat model of partial liver transplantation (LT) was used to demonstrate that thrombopoietin-induced thrombocytosis prior to surgery accelerated graft regeneration and improved the survival rate after transplantation. It was clarified that platelet-derived liver regeneration outweighed the associated risk of I/R injury after partial LT. Clinical strategies to increase perioperative platelet counts, such as thrombopoietin, thrombopoietin receptor agonist and platelet transfusion, may improve graft regeneration and survival after LDLT.

Keywords: Platelet; Liver transplantation; Regeneration; Ischemia/reperfusion injury; Kupffer cell; Oxidative stress

Core Tip: Perioperative thrombocytopenia is considered to be associated with poor graft regeneration and postoperative morbidity in the short and long term after living donor liver transplantation (LDLT). This review presented recent evidence for the role of platelets in LDLT based on clinical and basic studies. Platelets have both beneficial and detrimental effects on liver grafts, with a generally positive role in liver regeneration and a potentially negative role in ischemia/reperfusion injury. As increasing perioperative platelet counts are suggested to improve graft regeneration and survival, “platelet therapy” may provide prophylactic or therapeutic strategies to enhance the beneficial effects of LDLT.