title: Von Willebrand factor--cleaving protease activity in thrombotic microangiopathy after living donor liver transplantation: a case report.
abstract: Defective plasma activity of Von Willebrand factor (VWF)-cleaving protease (CP) and/or the inhibitors against this protease has been shown to have a pathological role in several forms of thrombotic microangiopathy (TMA). This report describes a patient for whom a diagnosis of TMA was made immediately after living donor liver transplantation. In this patient, activity of VWF-CP and its inhibitor were analyzed serially. At the onset of the disease, VWF-CP activity was quantified as 17%. Inhibitor against this protease was positive, with a titer of 0.6 Bethesda U/mL, and its inhibitory activity was quantified as 3.8 Bethesda U/mg immunoglobulin G. Laboratory parameters and clinical features were significantly improved after induction of plasma exchange (PE) with fresh frozen plasma and concurrent cessation of tacrolimus therapy. The inhibitors disappeared after one session of PE. However, VWF-CP activity after a transient increase and again decreased to subnormal levels after completion of PE. Nevertheless, this did not result in disease recurrence. In view of sustained VWF-CP activity at disease onset and the absence of definite correlations between levels of this protease and clinical features, abnormality of this enzyme system had no essential role in the pathogenesis of TMA in this case. Clinical findings suggest that TMA was tacrolimus-induced.
authors: First Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan. yuichi@hsp.md.shinshu-u.ac.jp
authors: Yuichi
authors: Y
authors: Nakazawa
authors: Yasuhiko
authors: Y
authors: Hashikura
authors: Koichi
authors: K
authors: Urata
authors: Toshihiko
authors: T
authors: Ikegami
authors: Masaru
authors: M
authors: Terada
authors: Hideo
authors: H
authors: Yagi
authors: Hiromichi
authors: H
authors: Ishizashi
authors: Masanori
authors: M
authors: Matsumoto
authors: Yoshihiro
authors: Y
authors: Fujimura
authors: Shinichi
authors: S
authors: Miyagawa
mesh_terms: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D000328:Adult; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000139:chemically induced / Q000201:enzymology* / Q000628:therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D017093:Liver Failure / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology; D019520:Living Donors; D008666:Metalloendopeptidases / Q000378:metabolism*; D010951:Plasma Exchange; D011184:Postoperative Period; D011697:Purpura, Thrombotic Thrombocytopenic / Q000139:chemically induced / Q000201:enzymology* / Q000628:therapy; D016559:Tacrolimus / Q000009:adverse effects; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D007166:Immunosuppressive Agents; D014841:von Willebrand Factor; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human; D016559:Tacrolimus