Dependence of platelet function on underlying liver disease in orthotopic liver transplantation.

OBJECTIVE: The purpose of the present study was to explore the platelet function during the perioperative period of orthotopic liver transplantation (OLT) due to the underlying liver disease. METHODS: The blood coagulation parameters, platelet surface markers and the determination of platelet aggregation were analyzed in 34 patients who underwent OLT. Blood samples were drawn preoperatively, anhepatic, 10 min and 1 hour after reperfusion, 1 day, 3 and 7 days postoperatively. Conventional coagulation screens, thrombopoietin (TPO) serum levels, P-selectin, GPIIb/IIIa and GPIb binding sites on the surface of platelets as evaluated by flow cytometry and platelet aggregation response were measured. RESULTS: Coagulation factors, maximum aggregation and rate of aggregation were significantly different before transplantation due to the underlying liver disease. Further we found a markedly depressed GPIIb/IIIa and P-selectin expression and a reduced rate of aggregation in all patients throughout the study. In contrast maximum aggregation of platelets was restored on the third day after reperfusion without intergroup differences and almost comparable to healthy controls. An inverse correlation was found between peripheral platelet count pre-transplantation and peak TPO concentrations one weak post-transplantation. CONCLUSIONS: In the entire process of OLT, coagulation factors, maximum aggregation and rate of platelet aggregation depend on the surgical phases during transplantation and on the underlying liver disease. The data obtained in this study might contribute to a better understanding of the pathophysiology and assessment of bleeding risk in OLT.

Renal transplantation normalized hydrogen peroxide production of neutrophils within the first day.

BACKGROUND: Hemodialysis patients are in a state of oxidant stress. In renal transplantation reactive oxygen species (ROS) are considered to be important factors of ischemia-reperfusion injury. Neutrophils produce ROS as part of the host defense against invading bacteria. This study was designed to investigate whether neutrophil function in hemodialysis patients is immediately affected by renal transplantation. METHODS: We evaluated the neutrophil respiratory burst and phagocytic activity in renal transplant patients with living-related donor (LRD) and cadaveric donor (CAD) grafts using flow cytometry techniques. Twenty patients (LRD = 6, CAD = 14) and 20 healthy volunteers were included in the study. Venous blood samples were drawn before anesthesia, 5 min before reperfusion, 1 h and 1, 3 and 7 days after reperfusion. RESULTS: Before surgery, a significant increase in hydrogen peroxide production in neutrophils was seen for both renal transplantation groups compared to healthy subjects. Within 24 h after reperfusion hydrogen peroxide production almost decreased to normal values. The phagocytic capacity of neutrophils was continuously depressed. There were no differences between the CAD and LRD groups. CONCLUSIONS: We found that the enhanced respiratory burst activity of patients with chronic renal failure decreased to normal values within 1 day following renal transplantation. Our results suggest that reduced respiratory burst activity resulting in a diminished risk of tissue damage by the uncontrolled production of ROS.

Platelet P-selectin and GPIIb/IIIa expression after liver transplantation and resection.

Platelet dysfunction contributes to haemostatic defects, possibly leading to bleeding complications. We hypothesised that liver transplantation and liver resection, together with portal clamping time, might be a potential stimulus for platelet activation. Therefore, we determined the expression of platelet GPIIb/IIIa and P-selectin, representing important platelet activation markers, and the thrombopoietin (TPO) serum level after transplantation and resection. Twenty patients [ten that had undergone orthotopic liver transplantation (OLT), ten with liver resection (LRX)] were included in the study. From sequential venous blood samples, surface expression of GPIIb/IIIa and P-selectin was quantified by flow cytometry, and TPO serum levels were determined by ELISA. Baseline GPIIb/IIIa receptor expression on circulating platelets was significantly reduced in the OLT group compared to the LRX group and healthy volunteers. GPIIb/IIIa expression after activation with TRAP-6 increased significantly ( P<0.001) in the LRX group but not in the OLT group. P-selectin expression after TRAP-6 stimulation increased significantly ( P<0.001) in the LRX group, being comparable to that in healthy volunteers, whereas only a very low increase in the OLT group was found. In the OLT group, TPO serum levels were in the lower normal range and rose above the upper limit of normal values 24 h after reperfusion. These data indicate that neither liver transplantation nor liver resection influences GPIIb/IIIa and P-selectin expression on circulating platelets. There was a lack of expression in cirrhotic patients and unimpaired baseline expression and functional reserve in non-cirrhotic liver-resection patients. After liver transplantation, increasing serum TPO levels, which indicated a recovering graft function, resulted in rising peripheral platelet counts.

Reduced P-selectin expression on circulating platelets after prolonged cold preservation in renal transplantation.

The uremic state in patients with terminal renal insufficiency is accompanied by a bleeding tendency connected with platelet dysfunction. Prolonged cold ischemia and inflammatory interactions between leukocytes, platelets and endothelial cells contribute to ischemia-/reperfusion (I/R) injury and may impair long-term graft survival. We evaluated the influence of the duration of cold preservation time on the expression of platelet GPIIb/IIIa and P-selectin and on the formation of leukocyte-platelet complexes after kidney transplantation. Fourteen patients undergoing kidney transplantation were divided into group I with long preservation time (26.6 +/- 1.9 h) and group II with short preservation time (8 +/- 6.1 h). Five venous blood samples (3 ml) were taken before induction of anesthesia, 12 h, 2, 7 and 14 d after transplantation. Surface expression of the GPIIb/IIIa, P-selectin and the percentage of platelet-granulocyte complexes were quantified by flow cytometry. Additionally blood from seven healthy volunteers was analyzed. GPIIb/IIIa and P-selectin expression on circulating platelets were significantly decreased in the long and the short-term graft preservation group compared with healthy volunteers. A significantly reduced P-selectin expression was found in the long-term preservation group compared with the short-term group. The percentage of platelet-granulocyte complexes also decreased in both preservation groups in the first 2 d after reperfusion and remained in this state in the long-term preservation group. Reduced expression of P-selectin on circulating platelets may be an indicator of I/R injury after prolonged kidney graft preservation.