Relevance of ADAMTS13 to liver transplantation and surgery

Figure 1 Plasma a disintegrin-like and metalloproteinase with throm-bospondin type-1 motifs 13 activity before and after living-related liver transplantation. Predominantly decreased ADAMTS13 activity could be fully restored after living-related liver transplantation in 6 out of 8 sick children with advanced cirrhotic biliary atresia (cases 1, 4, 5, 6, 7 and 8). Pre: Before transplantation; LRLT: Living-related liver transplantation; ADAMTS13: A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13.

Figure 2 Clinical course of 27-year-old male with Budd-Chiari syndrome after liver transplantation. Serum ALT level mildly increased on days 1 and 2 because of ischemia-reperfusion injury, decreased thereafter, but rapidly increased again on day 7 due to acute rejection (left panel). The platelet count decreased gradually and reached a nadir on day 7, when ADAMTS13 activity decreased markedly to less than 3% from 108% before surgery. After the administration of fresh frozen plasma and bolus injection of methylprednisolone (arrow), ALT level decreased and the platelet count gradually increased. The ADAMTS13 activity increased to 22% on day 14. After the first episode of acute rejection, VWF:Ag increased further and reached 368% on day 21, when ALT again increased due to a second episode of acute rejection. Bolus injection of methylprednisolone (arrow) led to a rapid decrease of ALT and a gradual increase in the platelet count. VWF:Ag decreased gradually, and ADAMTS13 activity finally recovered to 50% until day 98. Plasma UL-VWFM was detectable on day 1 at the time of ischemia-reperfusion injury, thereafter diminishing gradually during days 2 to 4, and again becoming evident on day 7 when acute rejection developed (right panel). The UL-VWFM disappeared transiently on day 9, but reappeared on day 11, coinciding with a mild increase of transaminase. UL-VWFM tended to diminish on day 15, but again became prominent on day 22 during the second episode of acute rejection. Pre: Before transplantation; NP: Normal plasma control; ALT: Alanine transaminase; LDH: Lactate dehydrogenase; FFP: Fresh frozen plasma; VWF: von Willebrand factor; UL-VWFM: Unusually large VWF multimers; ADAMTS13: A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13.

Figure 3 A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 activity before and after treatment for acute rejection in a liver transplant recipient. Decreased ADAMTS13 activity during acute rejection recovered after treatment for rejection. Pre: Before transplantation; FFP: Fresh frozen plasma; ALT: Alanine transaminase; LDH: Lactate dehydrogenase; ADAMTS13: A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13.

Figure 4 A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 activity according to blood occlusion time by Pringle’s maneuver. Pringle’s maneuver for long time (over 60 min: L) induced significantly profound decrease of ADAMTS13 activity, comparing to short (15-45 min: S) or no blood occlusion (N). The box shows the 25^th-75^th percentile, the bar indicates the median value, and the whiskers indicates the 5^th-95^th percentile. ^aP < 0.05 by ANOVA. ANOVA: Analysis of variance; ADAMTS13: A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13.

Figure 5 Perioperative changes of a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 activity and unusually large von Willebrand factor multimers in a patient with large hepatectomy. The patient underwent long Pringles’s maneuver (75 min). While ADAMTS13 did not decrease during hepatectomy even with long ischemic time by hepatic inflow occlusion, the activity markedly decreased until the next day. Consistently, UL-VWFM did not appeared during hepatectomy, and significantly up-regulated from day 3. Pre: Before transplantation; NP: Normal plasma controls; UL-VWFM: Unusually large von Willebrand factor multimers; ADAMTS13: A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13.

Figure 6 Hypothesis about mechanism of liver dysfunction via the local thrombotic thrombocytopenic purpura like mechanism. UL-VWFM: Unusually large von Willebrand factor multimers; ADAMTS13: A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13.