Idiopathic thrombotic thrombocytopenic purpura: strongest risk factor for relapse from remission is having had a relapse

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare, episodic clinical syndrome involving the production of thrombi in the microvasculature accompanied by thrombocytopenia and symptoms of organ ischemia. Idiopathic TTP develops when a patient produces antibodies that react with the protease ADAMTS13. The course after an episode is unpredictable; patients may relapse frequently or never. There is no laboratory value that can reliably predict potential relapse. STUDY DESIGN AND METHODS: To assess diagnostic and predictive values for risk of relapse, plasma samples from 27 patients with idiopathic TTP in remission were analyzed for anti-ADAMTS13 immunoglobulin (Ig)G, ADAMTS13 activity, and ADAMTS13 inhibitor titer. Patients were recruited at the Department of Hematology at the University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany. RESULTS: Anti-ADAMTS13 IgG was detected in 12 patients (44%); their median level of ADAMTS13 activity was nondetectable. Patients with anti-ADAMTS13 IgG had a median number of three previous relapses, whereas the 15 patients without presence of IgG (56%) had a median number of one previous relapse (p < 0.001; Mann-Whitney U test). The concentration of free anti-ADAMTS13 IgG and the levels measuring inhibitory activity (Bethesda unit) were positively correlated. CONCLUSION: A subgroup of TTP patients in remission with anti-ADAMTS13 IgG and nondetectable ADAMTS13 activity showed an increased risk for relapsing disease as demonstrated by their number of past relapses. The positive correlation we observed between anti-ADAMTS13 IgG and inhibitor levels supports the theory of ADAMTS13 inhibition as the crucial mechanism causing severe deficiency in ADAMTS13 activity in TTP.