A-175 Distribution of ADAMTS13 Inhibitor Levels as a Function of ADAMTS13 Activity

Background Thrombotic thrombocytopenic purpura (TTP) is diagnosed clinicopathologically that includes the finding of abnormally low ADAMTS13 activity (<0.1 IU/mL [10%]) in the context of appropriate laboratory and clinical findings. Patients with TTP may have autoantibodies that inhibits ADAMTS13 activity. Very little has been published on the presence of inhibitors in patients tested for presumed TTP. We undertook a study to understand the prevalence and distribution of inhibitor strength at low ADAMTS13 activity requiring reflex inhibitor testing. Methods We performed a retrospective review of a large commercial reference laboratory database and identified patients with initial testing for ADAMTS13 activity with reflex to inhibitor testing. ADAMTS13 activity was performed using the TECHNOZYM® ADAMTS-13 Activity enzyme-linked immunosorbent assay (ELISA). For samples with ADAMTS13 activity less than 0.31 IU/ml (31%), inhibitor levels were measured like that for inhibitor testing for factor VIII inhibitors. Inhibitor concentration was expressed in Bethesda Equivalent Units (BEUs). Inhibitor level distribution was described by determining the median, 5th, 25th, 75th, and 95th percentiles of results within each low bracket range of ADAMTS13 activity. Results We identified a total of 823 patients who were tested initially for ADAMTS13 activity with reflex to inhibitor. At ADAMTS13 activities of less than 0.03 IU/mL (3%), detectable inhibitor levels (0.4 BEU and above) were seen in at least 95% of patients. However, the median BEU dramatically fell when ADAMTS13 levels were 0.03 IU/mL (3%) or higher (Figure). Median inhibitor concentration was only 0.5 for patients with ADAMTS13 activities ranging from 0.03 to 0.10 IU/mL (3 to 10%) and <0.4 BEU (less then detectable) for patients with ADAMTS13 activities ranging from 0.11 to 0.30 IU/mL (11 to 30%). Conclusion ADAMTS13 inhibitors can be seen in most patients with ADAMTS13 activity less than 0.03 IU/mL (3%). However, detection of these inhibitors markedly decreases in patients with ADAMTS13 activity greater than 0.03 IU/mL (3%). Low ADAMTS13 activity with negative inhibitor requires clinical correlation and other supportive laboratory testing for the diagnosis of TTP.