Lower ADAMTS13 Activity and Higher Bethesda Units of Antibody Inhibitor in Early Remission Are Associated with a Higher Probability of TTP Exacerbation

An exacerbation of TTP is defined as a recurrence of TTP requiring therapy within 30 days of the last plasma exchange (PE). In contrast, the term relapse of TTP refers to a de novo event of TTP that by definition occurrs later than 30 days after the last PE.  Many researchers believe that an exacerbation probably represents the continuation of disease from an unresolved episode of TTP, thus making it a distinct clinical scenario worthy of investigation. 20-40% of patients with idiopathic TTP experience an exacerbation, resulting in the potential for considerable mortality and morbidity.  Biomarkers that can predict a patient's risk of exacerbation may help clinicians make correct decisions regarding the discontinuation of PE, immunotherapy, and the need to maintain or remove the central venous catheters required for PE. In this study, we used samples from our cohort of 36 patients with idiopathic TTP who were followed through their disease onset, treatment, remission, and recurrences.  First, we selected the pretreatment samples from a total of 61 episodes of TTP in the 36 patients, including both the initial and subsequent recurrences.  In eight of these 61 events, TTP exacerbation occurred after initial response to PE treatment. Second, we selected the early remission samples (the first week of remission after the discontinuation of PE therapy) from a total of 59 events (including both initial onset and recurrences).  In nine of these 59 events, TTP exacerbation occurred after the initial response to PE treatment. Next, we measured ADAMTS13 activity and Bethesda Units (BU) of ADAMTS13 inhibitors in both pretreatment and early remission samples. Finally, we used logistic regression analysis to evaluate the performance of these biomarkers with respect to the prediction of exacerbations of TTP. For pre-treatment samples, neither ADAMTS13 activity nor BU predicted the risk of exacerbation when comparing the exacerbation group (N=8) to the non-exacerbation group (N=53). In the early remission samples however, both ADAMTS13 activity and BU of antibody inhibitor demonstrated statistically significant differences between the exacerbation (N=9) and non-exacerbation (N=50) groups. The results are not influenced by the covariates of age, gender, and ethnicity.  In conclusion, severely deficient ADAMTS13 activity and elevated BU of ADAMTS13 inhibitors in early remission are highly associated with the probability of TTP exacerbation, providing the rationale for clinicians to either perform additional PE, add additional therapies, or delay the decision to remove the central venous catheter and monitor patients more closely for the need to re-initiate PE.