WB 06. Impact of ADAMTS13, Von Willebrand Factor-Cleaving Protease, on Hepatic Ischemia/Reperfusion

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H. Hirao, K. Hata, H. Tanaka, S. Kageyama, Y. Okamura, T. Kubota, S. Uemoto, O. Inamoto

Chair(s): Mustafa Cikirikcioglu, Frank Dor, Attila Szijarto, David J. Hackam, Cliff Shearman, Modise Koto, Yuzo Yamamoto

10:24 - 10:38h at Erszebet Room (A)

Categories: Walter Brendel Award, Hepatobiliary and Pancreatic Surgery

Session: Walter Brendel Award

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Background
Multimeric von-Willebrand factor is a well-known central player not only in physiological hemostasis but in pathological intravascular coagulation. Recently, much attention has been paid to its counteracting partner, ADAMTS13, as a Savior in various coagulation disorders, including thrombotic microangiopathy. Here we report the impact of ADAMTS13 on hepatic ischemia/reperfusion injury (IRI).

Material and Methods
Male wild type (WT) mice and ADAMTS13 knockout (KO) mice (8-10 weeks-old, 129/+Ter/SvJcl- TgH NCVC) were used. First, they were exposed to 70% partial hepatic ischemia for 60 minutes followed by either vehicle (Group-A: WT + vehicle and Group-B: KO + vehicle) or recombinant ADAMTS13 administration into KO mice intravenously (Group-C: KO + rADAMTS13). Hepatic microcirculation, measured by laser Doppler flowmetry, platelet count, serum transaminase release, liver histology and inflammatory cytokines were also examined.

Result
At 24 hours after reperfusion, hepatic microcirculation in Group-B fell down to 33.1% of the preischemic value, which was lower than in Group-A (69.8%, p<0.01). In Group-C, however, it was improved up to 67.4% (p<0.01). Immunohistochemistry with CD42b antibody revealed platelet aggregation in sinusoid in Group-B, which was improved by rADAMTS13 supplementation. In line, platelet counts (45.2 vs. 7.7 vs. 37.8 x105; p<0.05), ALT (5500 vs. 13964 vs. 8417; p<0.05) were all deteriorated in KO, but ameliorated by rADAMTS13 administration.

Conclusion
ADAMTS13 plays a considerable role in maintaining hepatic microcirculation, and its recombinant agent might be a novel therapeutic approach against hepatic IRI.