Low levels of ADAMTS‐13 with high anti‐ADAMTS‐13 antibodies during remission of immune‐mediated thrombotic thrombocytopenic purpura highly predict for disease relapse: A multi‐institutional study

Abstract

Immune‐mediated thrombotic thrombocytopenic purpura (iTTP) is a life‐threatening immune‐mediated thrombotic microangiopathy. Daily therapeutic plasma exchange (TPE) and the optimized use of rituximab have strikingly improved the outcome of this disease, however the rate of disease recurrence remains high. Specific predictors of relapse in patients in remission can be relevant for an optimal patient management. In this study, we aimed to identify predictive variables of disease relapse in a multicenter cohort of 74 out of 153 iTTP patients. They were tested at different time points during remission for the levels of ADAMTS‐13 activity and autoantibody, and did not receive pre‐emptive treatment for ADAMTS‐13 activity deficiency during remission. The results showed that the association of ADAMTS13 activity ≤20% with a high anti‐ADAMTS‐13 titer at remission, and the time to response to first line treatment ≥13 days, were independent predictive factors of disease relapse. In addition, the use of rituximab in patients with exacerbation or refractoriness to TPE was significantly associated with reduced relapse rate. By Cox regression analysis, patients with ADAMTS‐13 activity ≤20% plus anti‐ADAMTS13 antibody titer ≥15 U/mL at remission had an increased risk of relapse (HR 1.98, CI 95% 1.087‐3.614; P < .02). These findings may help to outline more personalized therapeutic strategies in order to provide faster and sustained responses to first‐line iTTP treatment and prevent relapses in these patients.

Incidence, diagnosis, and outcome of immune‐mediated thrombotic thrombocytopenic purpura: A nationwide survey by the Spanish registry of thrombotic thrombocytopenic purpura

“…The risk of long‐term relapse is a strong argument for monitoring iTTP patients, and ADAMTS13 is the marker with the highest ability to predict this 16 . According to the survey, ADAMTS13 activity and the inhibitor were determined during episodes in around 66.7% and 45.9% of patients, and, between episodes, in 80% and 65% of Spanish iTTP patients, respectively.…”

SARS-CoV-2 vaccination and immune thrombotic thrombocytopenic purpura

“…Our combined cohort is relatively mature, and we offer preemptive rituximab to patients with ADAMTS13 activity <20% during clinical remission, which may explain the high pre-vaccination ADAMTS13 activity and corresponding low relapse rate. Patients in clinical remission without ADAMTS13 remission 20 might be at increased risk for relapse 21,22 following COVID-19 vaccination. We check ADAMTS13 activity every 3 months in all patients to estimate risk of recurrence (including post-vaccination).…”

Hemostatic Profile and Serological Response of Patients with Immune Thrombotic Thrombocytopenic Purpura after Receiving BNT162b2 Vaccine: A Prospective Study

“…ADAMTS-13 activity and anti-ADAMTS-13 IgG antibodies were tested by a commercially available ELISA kit (Technoclone, Vienna, Austria) as described. 23 Activity values below 10% and between 11 and 50% were considered "severely" and "moderately" reduced, respectively, while values greater than 50% were considered normal. A negative value for anti-ADAMTS-13 IgG consisted of an antibody titer <15 U/mL.…”