title: Plasma ADAMTS13 activity may predict early adverse events in living donor liver transplantation: observations in 3 cases.
abstract: A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) is a metalloproteinase that specifically cleaves the multimeric von Willebrand factor (VWF). Deficiency of ADAMTS13 increases the unusually large VWF multimers (UL-VWFM), which leads to platelet clumping and/or thrombus formation, resulting in microcirculatory disturbance. We serially determined the activity of plasma ADAMTS13, together with VWF antigen (VWF:Ag) and UL-VWFM, in association with the development of early graft dysfunction in 3 liver transplant recipients and 4 patients with major hepatectomy as controls. In case 1, ADAMTS13 activity decreased markedly from 108% to less than 3% with concomitant thrombocytopenia on posttransplantation day 7, when acute rejection occurred. Simultaneously, UL-VWFM were detected. During the second episode of rejection, VWF:Ag increased to 368% with the appearance of UL-VWFM, while ADAMTS13 activity was as low as 18%, indicating an imbalance between a large amount of UL-VWFM and low activity of ADAMTS13. Administration of fresh frozen plasma (FFP) together with treatment for acute rejection resulted in an improvement of ADAMTS13 activity and disappearance of the UL-VWFM. In case 2, ADAMTS13 activity promptly decreased to 9% with thrombocytopenia on day 1, when ischemia-reperfusion injury occurred. Subsequently, the ADAMTS13 activity increased steadily without appearance of UL-VWFM, and the patient recovered uneventfully. ADAMTS13 activity decreased to 15% immediately after transplantation in case 3 as well. In contrast, ADAMTS13 activity never decreased below 20% in 4 patients with major hepatectomy as controls. In conclusion, these results indicate that the kinetics of ADAMTS13 and UL-VWFM could be good indicators of adverse events after liver transplantation. Our findings not only suggest a novel mechanism for thrombocytopenia, but also provide a useful tool for diagnosis of graft dysfunction in the early stage after transplantation.
authors.affiliation: Department of Surgery, Nara Medical University, Kashihara, Nara, Japan. saihoko@naramed-u.ac.jp
authors.forename: Saiho
authors.initials: S
authors.lastname: Ko
authors.forename: Eiji
authors.initials: E
authors.lastname: Okano
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Kanehiro
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Ishizashi
authors.forename: Masahito
authors.initials: M
authors.lastname: Uemura
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimura
authors.forename: Koichi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nakajima
mesh_terms: D051722:ADAM Proteins / Q000097:blood*; D000071120:ADAMTS13 Protein; D000328:Adult; D006498:Hepatectomy; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D013921:Thrombocytopenia / Q000209:etiology; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human