Abstract
Background: A severe form of acute pancreatitis, severe acute pancreatitis (SAP), frequently develops pancreatitis-associated multiorgan failure (MOF) followed by systemic microcirculatory disturbance with a high mortality. ADAMTS13 has been focused on the occurrence of thrombotic thrombocytopenic purpura (TTP). TTP has been reported to cause acute pancreatitis in a few percents, and recent study indicates that some acute pancreatitis may be a triggering event for TTP. We sequentially determined plasma ADAMTS13 activity (ADAMTS13:AC) and its related parameters in patients with SAP, and thereby, tried to explore their potential role on the development of MOF.
Methods: Subjects studied were 13 patients with SAP, who were admitted into the department of emergency and critical care medicine of our hospital. The etiology was alcohol in 7, idiopathic in 3, common bile duct stones in 2, and post endoscopic retrograde cholangiopancreatography in 1. Eleven patients were survivors and two were non-survivors. Two of 4 patients with MOF were non-survivors. The severity was scored according to APACHE-II system. ADAMTS13:AC was determined using a commercially available ADAMTS13-act-ELISA (Kainos Inc., Tokyo). Plasma levels of VWF antigen (VWF:AG), interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis-α (TNF-α) were measured by ELISA. Unusually large VWF multimer (UL-VWFM) was analyzed by a vertical SDS -1.0% agarose gel electrophoresis system.
Results: ADAMTS13:AC significantly decreased at day 1 (mean 39%, p<0.001) and at day 2 (33%, p<0.001) as compared to healthy subjects (99%). The activity, thereafter, gradually recovered (49% at day 5, 58% at day 7, and 70% at day 10) in survivors, whereas in non-survivors, it decreased from 22% at day 1 to 10% at day 2 in one and showed 15% at day 1 in another. The inhibitor against ADAMTS13 was not detected. The VWF:AG increased to 402% at day 1 (p<0.001) and 333% at day 2 (p<0.001) as compared to healthy subjects (100%), and the value, thereafter, remained high (395% at day 5, 428% at day 7, and 382% at day 10). The UL-VWFM could be detected in 7 cases for 3 to 35 days immediately after admission. On admission, patients with detectable UL-VWFM tended to be lower ADAMTS13:AC and higher VWF:Ag than those without, resulting in higher VWF/ADAMTS13 ratio (19.9 vs. 8.9, p<0.01). Patients with MOF showed lower ADAMTS13:AC (20% vs. 40%, p<0.05) and higher VWF:Ag (448% vs. 391%, p<0.05) than those without, resulting in higher VWF/ADAMTS13 ratio (22.9 vs. 11.2, p<0.02). The concentrations of IL-6, IL-8, and TNFα increased, and ADAMTS13:AC correlated with those of IL-6 (r= − 0.51, p<0.05) and IL-8 (r= − 0.66, p<0.02). Furthermore, ADAMTS13:AC negatively correlated with APACHE-II score (r= − 0.67, p<0.02).
Conclusion: Markedly decreased ADAMTS13:AC together with increased amounts of UL-VWFM was closely related to the severity of pancreatitis, an intense systemic inflammatory response, and prognosis in patients with SAP. These results indicate that the imbalance between the enzyme and its substrate may involve in the development of acute pancreatitis and subsequent MOF through enhanced thrombogenesis.
Author notes
Disclosure: No relevant conflicts of interest to declare.
