Platelet hyperaggregability is associated with decreased ADAMTS13 activity and enhanced endotoxemia in patients with acute cholangitis.

ABSTRACT

AIM: Insufficient ADAMTS13 activity (ADAMTS13AC) leads to increased levels of unusually large von Willebrand factor (VWF) multimers and causes microcirculatory disturbance and multiple organ failure (MOF). Endotoxin (Et) triggers the activation of coagulation and cytokine cascades, leading to MOF in severe inflammatory response syndrome. Here, we investigated the potential role of endotoxemia-related ADAMTS13 in acute cholangitis. METHODS: Twenty-four patients with acute cholangitis, including 7 with severe acute cholangitis, were recruited in this study. The levels of ADAMTS13AC, VWF antigen (VWFAg), interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α in each patient were determined by enzyme-linked immunosorbent assay, whereas Et levels were determined by Et activity assay (EAA) analysis. RESULTS: The ADAMTS13AC and VWFAg levels were significantly lower and higher, respectively, in patients with acute cholangitis than in controls. The EAA levels were higher in patients with acute cholangitis than in controls, and were inversely correlated with that of ADAMTS13AC. Patients with severe acute cholangitis had significantly lower ADAMTS13AC and higher VWFAg levels than those with mild to moderate cholangitis. Notably, ADMTS13AC was directly correlated with platelet counts and inversely correlated with IL-6 levels, and the VWFAg/ADAMTS13AC ratio was directly correlated with IL-8 and TNF-α levels. CONCLUSIONS: Imbalance of ADAMTS13AC and VWFAg levels might be associated with severe acute cholangitis, reflecting platelet hyperaggregability. Severe acute cholangitis has severe pathophysiological features and is complicated by endotoxemia and MOF. Notably, this is the first report indicating an association between the levels of ADAMTS13AC and VWFAg and those of EAA and cytokines in acute cholangitis.