Ischaemia-reperfusion injury with Pringle's maneuver induces unusually large von Willebrand factor multimers after hepatectomy

Introduction: von Willebrand factor (VWF) is synthesised in vascular endothelial cells and released into the plasma as unusually large VWF multimers (UL-VWFMs). Sinusoidal endothelial cells are a major target of ischaemia-reperfusion injury due to liver surgery. This study aimed to clarify the effect of hepatectomy on UL-VWFMs. Materials and methods: Thirty-five patients who underwent hepatectomy were eligible for the study. Plasma ADAMTS13 activity and VWF antigen levels were measured by enzyme-linked immunosorbent assay and multimer analysis of plasma VWF was performed according to Ruggeri and Zimmerman's method. For analyses, patients were categorised according to UL-VWFM positivity after hepatectomy. Results: Plasma ADAMTS13 activity significantly decreased from 61.0% (27.7%-126.2%) before operation to 37.4% (20.2%-71.4%) on postoperative day 7 (p < 0.001). Plasma VWF antigen levels significantly increased from 172.1% (80.5%-412.8%) before operation to 361.0% (154.7%-745.8%) on postoperative day 2, which remained high until postoperative day 7 (p < 0.001). Seven patients remained UL-VWFMs-negative and 22 patients became UL-VWFMs-positive after operation. Pringle's maneuver duration was significantly longer and blood loss volume was significantly higher in the UL-VWFMs-positive group (p= 0.001 and p= 0.003, respectively). By multivariable analysis, Pringle's maneuver duration [odds ratio 1.049, 95% confidence interval (CI) 1.001-1.098; p= 0.043] was significantly associated with increased UL-VWFMs level after hepatectomy. UL-VWFMs index was significantly correlated with Pringle's maneuver duration (r= 0.444, p= 0.017). Conclusions: Plasma UL-VWFMs levels increased after hepatectomy due to ischaemia-reperfusion injury with Pringle's maneuver.