Abstract 685: Reduced von Willebrand Factor-cleaving Protease (ADAMTS13) Activity in Acute Myocardial Infarction
Backgrounds: High plasma levels of von Willebrand factor (VWF) are associated with an increased risk of acute myocardial infarction (AMI). The hemostatic activity of VWF is strongly dependent on its multimeric structure, with the highest activity in unusually large VWF multimers (ULVWF). Recent studies have shown that ULVWF is regulated by VWF-cleaving protease (ADAMTS13). The aim of this study was to examine the relationship between VWF and ADAMTS13 levels in plasma and coronary thrombi in patients with AMI.
Methods and Results: Plasma VWF antigen, ADAMTS13 antigen and activity levels (mU/ml) were examined in 41 patients with AMI, 33 with stable exertional angina (SEA) and 30 with chest pain syndrome (CPS). Plasma VWF and ADAMTS13 antigen levels were measured by ELISA. ADAMTS13 activity was measured by detecting fluorescence intensity obtained from the mixture with FRETS-VWF73. Plasma VWF antigen levels increased significantly in patients with AMI compared with SEA and CPS on admission (2151 ± 97, 1445 ± 93 and 1425 ± 76, respectively; P < 0.0001 in AMI vs SEA and CPS). Plasma ADAMTS13 antigen and activity levels were significantly lower in patients with AMI than in those with SEA and CPS (799 ± 29, 996 ± 31 and 967 ± 31 in antigen levels, respectively; P < 0.01 in AMI vs SEA and CPS, 768 ± 27, 893 ± 27 and 936 ± 29 in activity levels, respectively; P < 0.01 in AMI vs SEA and CPS). There were significant inverse correlations between VWF antigen and ADAMTS13 antigen or activity levels (r = −0.453, P < 0.0001; r = −0.447, P < 0.0001; respectively). Ratio of VWF antigen/ADAMTS13 antigen was significantly higher in patients with AMI (P < 0.0001) compared to SEA and CPS, while it was significantly higher in AMI patients with in-hospital outcome events (P = 0.0029) than in those without. Immunohistchemistry using coronary thrombi obtained from AMI patients revealed that ADAMTS13 antigen was localized at the site of VWF, platelet accumulation and fibrin deposition.
Conclusions: These findings suggested that the decrease of plasma ADAMTS13 levels in AMI patients might be due to its consumption by increased VWF activity. Plasma ADAMTS13 levels might be a useful regulatory marker for some disease states accompanied by enhanced VWF antigen levels such as coronary thrombus formation in AMI.