Among patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP), ADAMTS13 with an open confirmation (open ADAMTS13) appears to be a novel diagnostic biomarker among Japanese patients, according to research published in Blood Advances. The authors noted, furthermore, that this biomarker may be useful across ethnic cohorts.

A rare disorder, iTTP is linked with severe thrombocytopenia, microangiopathic hemolytic anemia, and systemic microvascular thrombi. Although the diagnosis of iTTP is clear where ADAMTS13 levels are less than 10% and there is evidence of anti-ADAMTS13 autoantibodies, the diagnosis can be unclear where ADAMTS13 activity is between 10% and 20%. Biomarkers for correct diagnosis where iTTP is a possibility are therefore needed.

There is, however, some evidence that open ADAMTS13 may aid in diagnostic decision-making where ADAMTS13 activity is between 10 and 20%, though all studies to date have been performed mainly in White populations. For this study, researchers aimed to determine the diagnostic power of open ADAMTS13 in a group of Japanese patients with iTTP.

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Overall, 195 samples from 195 Japanese patients with iTTP were evaluated. In this cohort, the median age was 55 years, the male to female ratio was 111:84, and 166 and 25 patients had primary and secondary iTTP, respectively.

Analysis showed that 94.7% of the 76 samples with detectable ADAMTS13 antigen levels had evidence of open ADAMTS13. Furthermore, the authors noted a link between ADAMTS13 inhibitor titers and anti-ADAMTS13 immunoglobulin G autoantibody titers.

Further analysis suggested that patients with autoantibodies against the 6 ADAMTS13 fragments evaluated in this study had a higher risk of disease-related death (P = .02).

“In conclusion, our data validated the use of open ADAMTS13 as a biomarker in the diagnosis of iTTP in the Japanese iTTP cohort and confirmed the value of immunprofiling of anti-ADAMTS13 autoantibodies to further develop targeted therapies in iTTP,” the authors wrote in their report. “Additional studies in other ethnic cohorts will further expand our knowledge on ADAMTS13 conformation and immunoprofiles.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 


Sakai K, Matsumoto M, De Waele L, et al. ADAMTS13 conformation and immunoprofiles in Japanese patients with immune-mediated thrombotic thrombocytopenic purpura. Blood Adv. 2023;7(1):131-140. doi:10.1182/bloodadvances.2022008885