ADAMTS-13 activity in the presence of elevated von Willebrand factor levels as a novel mechanism of residual platelet reactivity in high risk coronary patients on antiplatelet treatment

Background: The pathophysiologic mechanisms leading to residual platelet reactivity (RPR) on antiplatelet therapy, a condition high prevalent in patients with acute coronary syndrome, are not yet elucidated. In the acute phase of coronary artery disease large amounts of ultra large VWF multimers (ULVWF) are released and cleaved by the activity of ADAMTS-13. Objective: Aim of this study was to evaluate the relationships between VWF antigen (VWF:Ag) levels, collagen binding activity of VWF (VWF:CB), ADAMTS-13 and interleukin-6 (IL-6) levels in affecting platelet response to dual antiplatetet treatment. Methods: In 159 acute coronary syndrome (ACS) patients undergoing percutaneous coronary interventions we measured platelet function by platelet aggregation with two agonists [1 mM arachidonic acid (AA) and 10 mu M ADP]. We defined patients with RPR those with platelet aggregation by AA >20% and/or ADP (10 mu mol) >70%. Results: We found significantly lower ADAMTS-13 activity, elevated IL-6, VWF:Ag and VWF:CB levels in patients with RPR. A lower ADAMTS-13 activity was present in patients with VWF:Ag and VWF:CB in the upper tertile. At the multivariate analysis ADAMTS-13 activity and IL-6 were independent risk factors for RPR. Conclusion: Our results indicate that ADAMTS-13 activity and IL-6 levels independently affect RPR and suggest that, by different pathways, both are involved in the variable response to antiplatelet therapy. (C) 2008 Elsevier Ltd. All rights reserved.