The correlation between platelet activation and liver injury by conditioning and bone marrow transplantation

Hepatic veno-occlusive disease (HVOD) is a common severe complication after transplantation which is closely related to liver sinusoidal endothelial cell (LSEC) injury. Although platelet activation might play a key role in the progress of HVOD, the relationship between the P-selectin and HVOD is still unclear. In this study, the P-selectin, liver functions, and observed damage of LSEC after transplantation were detected. The P-selectin, alanine aminotransferase (ALT) and bilirubin were first detected in the patients. The ALT of patients reached the first peak of 144 ± 45.04 U/L, on day 7 after busulfan + cyclophosphamide (BU/CY) pretreatment, and reached the second peak of 220.5 ± 40.58 U/L on day 7 after transplantation. Similarly, the concentration of bilirubin increased BU/CY pretreatment and reached peak on day 15 after transplantation at 38.8 ± 5.99 μmol/L. However, the level of P-selectin was significantly higher than normal levels for a long time and peaked on day 3 after BU/CY pretreatment and on day 12 after transplantation (P < .05). Then the P-selectin, liver function, liver index, hepatocytes, and LSEC were observed using a transplantation model of C57BL/6 (H-2(b)) donor to BALB/c (H-2(d)) recipient. The P-selectin, liver index, and liver function of total body irradiation (TBI) mice and bone marrow transplantation (BMT) mice were significantly increased, but the increase of TBI mice were more significant. On day 5, the ratio of TBI mice peripheral blood platelets which expressed P-selectin was higher and reached an earlier peak at 15.6 ± 2.63%, whereas that of BMT mice was 6.59 ± 1.17%, and peaked on day 15 at 8.36 ± 1.55% (P < .05). Moreover, the ALT and bilirubin levels of TBI mice were higher and reached earlier peaks on day 5 at 58.65 ± 1.43 U/L and 27.14 ± 1.32 μmol/L, respectively, whereas those of BMT mice peaked on day 5 at 50.22 ± 2.02 U/L and day 30 at 39.57 ± 1.55 μmol/L, respectively (P < .05). The LSEC damage and hepatocyte edema in BMT mice were most serious at day 15, and at day 30 injuries did not allow recovery. The liver score of TBI mice peaked on day 5, whereas that of BMT mice peaked on day 15. Moreover, the degree of damage and platelet activation positively correlated. This study implied that P-selectin could be used as a predictor of HVOD.