ADP-dependent platelet function prior to and in the early course of pediatric Liver transplantation and persisting thrombocytopenia are positively correlated with ischemia/reperfusion injury

Abstract

Summary Little is known about the role of platelets in relation to ischemia/reperfusion injury (IRI) of the liver graft especially in children. Thrombocyte function was prospectively analysed in 21 consecutive pediatric liver transplantation (pLT) patients by platelet aggregometry secondary to adenosine diphosphate (ADP), collagen, and the von Willebrand factor activator ristocetin (VWF:rco). Post‐OP serum levels of ALT were used to divide patients into groups with high (highHD, n = 8) and low (lowHD, n = 13) hepatocellular damage. Clinically, highHD‐patients showed impaired plasmatic coagulation and elevated serum bilirubin levels early after pLT when compared with lowHD‐patients. Further, platelet counts markedly decreased between pre‐OP and postreperfusion (postrep.) in the highHD group (P = 0.003) and did not recuperate by POD6. In lowHD individuals thrombocytopenia improved from both pre‐OP (P < 0.05) and postrep. (P < 0.001) respectively towards POD6. Experimental thrombocyte testing revealed that before graft reperfusion only ADP‐dependent platelet aggregation correlated with reperfusion injury, thrombocytopenia and early graft function. During the first 48 h after graft reperfusion, all inducers tested demonstrated elevated platelet aggregation levels in the highHD group. Our data suggest a possible role of platelets and their aggregative status in liver IRI subsequent to clinical pLT. Reperfusion‐independent ADP‐triggered platelet function may be a determinant for IRI in the pediatric hepatic graft recipient.

Potential factors influencing the development of thrombocytopenia and consumptive coagulopathy after genetically modified pig liver xenotransplantation

“…In summary, although there may be several factors influencing the development of thrombocytopenia after liver TX [42–44], activation of platelets and severe thrombocytopenia remain a major hurdle for successful pig‐to‐primate liver xenoTX. We provide some evidence suggesting that thrombocytopenia and CC is not initiated by activation of graft endothelium in response to the immune response, but that activation of recipient platelets occurs after exposure of the platelets to graft ECs.…”

Ischemia reperfusion-facilitated sinusoidal endothelial cell injury in liver transplantation and the resulting impact of extravasated platelet aggregation

“…Remarkably, superior adenosine diphosphate (ADP)-dependent aggregative levels of platelets prior to graft reperfusion were demonstrated to be positively correlated with serum markers for hepatocellular reperfusion damage. Schulte et al reported that a certain increase in the ADP-dependent functional status of platelets in the pediatric recipients of liver grafts may result in a critical promotion of platelet adherence and activation in liver graft LSECs following reperfusion [ 16 , 20 ]. Platelet accumulation in the postischemic microvasculature might significantly contribute to the manifestation of hepatic I/R injury [ 14 ].…”

“…Platelet recruitment and subsequent activation might play an important role in the pathogenesis of hepatic I/R injury [ 14 ]. Platelet aggregation also correlated with reperfusion injury, thrombocytopenia and early graft dysfunction in liver transplantation [ 16 ]. As such, persistent thrombocytopenia after reperfusion is an unfavorable indicator for early liver graft dysfunction [ 17 ].…”

Platelets Boost Recruitment of CD133+ Bone Marrow Stem Cells to Endothelium and the Rodent Liver—The Role of P-Selectin/PSGL-1 Interactions

“…Interestingly, we recently demonstrated CD133 + BMSC when co-incubated with platelets to control their thrombogenic responses in a CD39-dependent manner [ 8 ]. Furthermore, a major role for platelets was described in the mediation of hepatic injury [ 9 , 10 , 11 ]. There is increasing evidence that points to a crucial complex orchestrated role for platelets in various preclinical and clinical scenarios of hepatic regeneration following injury and resection, respectively [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ].…”