Uemura Masahito, Fujimura Yoshihiro, Matsumoto Masanori, Ishizashi Hiromichi, Kato Seiji, Matsuyama Tomomi, Isonishi Ayami, Ishikawa Masatoshi, Yagita Masato, Morioka Chie, Yoshiji Hitoshi, Tsujimoto Tatsuhiro, Kurumatani Norio, Fukui Hiroshi
Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan.
Thromb Haemost. 2008 Jun;99(6):1019-29. doi: 10.1160/TH08-01-0006.
Decreased plasma ADAMTS13 activity (ADAMTS13:AC) results in the accumulation of unusually large von Willebrand factor multimer (UL-VWFM) and the formation of platelet thrombi. It remains controversial whether or not plasma ADAMTS13:AC decreases in patients with liver cirrhosis (LC), and its relationship to clinical features has not been fully investigated. We measured ADAMTS13:AC and its related parameters in plasma in 33 patients with chronic hepatitis (CH) and in 109 patients with LC. ADAMTS13:AC decreased with increasing severity of liver disease (controls means 100%, CH 87%, Child A-LC 79%, Child B-LC 63%, and Child C-LC 31%), and showed severe deficiency (<3% of controls) in five end-stage LC. Activities measured by act-ELISA strongly correlated with those determined by the VWFM assay and ADAMTS13 antigen. Multivariate analysis showed Child-Pugh score and spleen volume independent factors contributing to ADAMTS13:AC. VWFM patterns were normal in 53% of cases, degraded in 31%, and unusually large in 16%. Patients with unusually large VWFM had the lowest ADAMTS13:AC as well as the highest Child-Pugh score, serum creatinine and blood ammonia levels. Plasma inhibitor against ADAMTS13 detected in 83% of patients with severe to moderate ADAMTS13:AC deficiency mostly showed marginal zone between 0.5 and 1.0 BU/ml. The IgG-type autoantibodies specific to plasma derived-ADAMTS13 was detected by Western blot in only five end-stage LC with severe ADAMTS13:AC deficiency. In conclusion, both plasma ADAMTS13 activity and antigen levels decreased with increasing severity of cirrhosis. An imbalance between the decreased ADAMTS13:AC and its increased substrate may reflect the predisposing state for platelet thrombi formation in patients with advanced LC.
血浆中ADAMTS13活性（ADAMTS13:AC）降低会导致异常大的血管性血友病因子多聚体（UL-VWFM）积聚并形成血小板血栓。肝硬化（LC）患者血浆ADAMTS13:AC是否降低仍存在争议，且其与临床特征的关系尚未得到充分研究。我们检测了33例慢性肝炎（CH）患者和109例LC患者血浆中的ADAMTS13:AC及其相关参数。ADAMTS13:AC随着肝病严重程度的增加而降低（对照组为100%，CH为87%，Child A-LC为79%，Child B-LC为63%，Child C-LC为31%），5例终末期LC患者表现为严重缺乏（<对照组的3%）。通过act-ELISA测定的活性与通过VWFM检测法和ADAMTS13抗原测定的活性密切相关。多因素分析显示Child-Pugh评分和脾脏体积是影响ADAMTS13:AC的独立因素。53%的病例VWFM模式正常，31%降解，16%异常大。VWFM异常大的患者ADAMTS13:AC最低，Child-Pugh评分、血清肌酐和血氨水平最高。在83%的中重度ADAMTS13:AC缺乏患者中检测到血浆ADAMTS13抑制物，大多在0.5至1.0 BU/ml之间呈边缘区。仅在5例ADAMTS13:AC严重缺乏的终末期LC患者中通过Western blot检测到针对血浆来源ADAMTS13的IgG型自身抗体。总之，随着肝硬化严重程度的增加，血浆ADAMTS13活性和抗原水平均降低。ADAMTS13:AC降低与其底物增加之间的失衡可能反映了晚期LC患者血小板血栓形成的易患状态。
