Decreased activity of plasma ADAMTS13 are related to enhanced cytokinemia and endotoxemia in patients with acute liver failure.

Deficient ADAM metalloproteinase with thrombospondin type-1 motif, member 13 (ADAMTS13) activity (ADAMTS13:AC) results in the accumulation of unusually large von Willebrand factor multimers (UL-VWFM) and causes microcirculatory disturbances and multiple organ failure, while endotoxins trigger the activation of a coagulation cascade. The objective of the present study was to explore the role of ADAMTS13 in endotoxemia in patients with acute liver failure (ALF). Plasma concentrations of endotoxin and cytokines, including interleukin (IL)-6 and IL-8, and activity of the plasma ADAMTS13 inhibitor were determined, along with ADAMTS13:AC, the VWF antigen (VWF:Ag) and UL-VWFM, in 27 patients with acute hepatitis (AH), 11 patients with ALF, and 10 healthy controls. IL-6 and IL-8 concentrations on admission were significantly higher in patients with ALF than in those with AH or in healthy controls. ADAMTS13:AC concomitantly decreased and VWF:Ag progressively increased with increasing cytokine concentrations from the normal range to >100 pg/ml. The inhibitor was detected in 8 patients with ALF (0.6 to 2.4 BU/ml) and 6 patients with AH (0.6 to 0.8 BU/ml). Patients with the inhibitor reported lower ADAMTS13:AC, higher VWF:Ag and lower functional liver capacity than those without the inhibitor. Collectively, the findings suggested that decreased ADAMTS13:AC and increased VWF:Ag may be induced by pro-inflammatory cytokinemia as well as the presence of the ADAMTS13 inhibitor, both of which may be closely related to enhanced endotoxemia in patients with ALF.