Mechanism underlying severe de ficiency of plasma ADAMTS-13 activity in immune thrombotic thrombocytopenic purpura

Background: Immune-mediated thrombotic thrombocytopenic purpura is caused by autoantibodies against ADAMTS-13, a plasma enzyme that cleaves von Willebrand factor. However, the mechanism resulting in severe de ficiency of plasma ADAMTS-13 activity remains controversial. Objectives: To determine the mechanism of autoantibody-mediated severe de ficiency of plasma ADAMTS13 activity in immune-mediated thrombotic thrombocytopenic purpura. Methods: Fluorescence resonance energy transfer-VWF73 was used to determine plasma ADAMTS-13 activity. Enzyme-linked immunosorbent assay (ELISA) was used to determine anti -ADAMTS-13 immunoglobulin G. ELISA and capillary electrophoresis - based Western blotting were employed to assess plasma ADAMTS-13 antigen. Results: We showed that plasma ADAMTS-13 antigen levels varied substantially in the samples collected on admission despite all showing plasma ADAMTS-13 activity of <10 IU/dL (or <10% of normal level) using either ELISA or Western blotting. More severe de ficiency of plasma ADAMTS-13 antigen ( <10%) was detected in admission samples by ELISA than by capillary Western blotting. There was a signi ficant but moderate correlation between plasma ADAMTS-13 activity and ADAMTS-13 antigen by either assay method, suggesting that severe de ficiency of plasma ADAMTS-13 activity is not entirely associated with low levels of ADAMTS-13 antigen. Conclusion: We conclude that severe de ficiency of plasma ADAMTS-13 activity primarily resulted from antibody-mediated inhibition, but the accelerated clearance of plasma ADAMTS-13 antigen via immune complexes may also contribute signi ficantly to severe de ficiency of plasma ADAMTS-13 activity in a subset of patients with acute immune-mediated thrombotic thrombocytopenic purpura.