Updated guidance from an International Working Group (IWG) published in Blood revises clinically relevant definitions in the immune-mediated thrombotic thrombocytopenic purpura (iTTP) setting, although the guidance requires prospective validation.

iTTP, a thrombotic microangiopathy characterized by severe ADAMTS13 activity deficiency, is linked to thrombocytopenia with mechanical hemolysis, microvascular thrombosis, and ischemic organ injury. ADAMTS13, which is necessary for cleavage of the ultra-large multimers of von Willebrand factor (VWF), is frequently used, and is sufficient, for diagnosis of iTTP.

When clinical outcome definitions for iTTP were first proposed in 2003, therapeutic plasma exchange (TPE) and corticosteroids were standard initial treatments; monoclonal antibodies had been discovered, but had not yet been clinically evaluated in this setting.

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The relevance of ADAMTS13 activity deficiency to patient response had, furthermore, only been recently reported, and was not typically evaluated as a part of clinical practice; platelet counts were the primary means of response evaluation.

At this point, a response to treatment was defined as attainment of a normal platelet count. Durable remission was defined as achievement of a sustained normal platelet count for 30 days after TPE discontinuation.

While these definitions were revised by an IWG in 2017, the advent of new treatments, as well as the widespread availability of ADAMTS13 activity measurement, necessitates further revisions. In light of these changes, the researchers attempted to revise clinically relevant definitions.

The authors revised definitions to effectively distinguish clinical remission/relapse and ADAMTS13 remission/relapse, and to incorporate the consequences of anti-VWF therapy. The revised definitions include the following:

  • Response – a sustained platelet count of at least 150 x 109/L, lactate dehydrogenase levels of less than 1.5 times the upper level of normal, and no evidence of novel or progressing organ injury
  • Exacerbation – after a clinical response and before clinical remission, platelet counts of below 150 x 109/L within 30 days of anti-VWF or TPE discontinuation

However, prospective validation has yet to be carried out. “We hope that these updated definitions will be useful in clinical practice and will serve as a template for standardized definitions in iTTP research,” the study authors wrote. “Undoubtedly, further revisions will be required in the future to keep pace with the inexorable advances in our understanding and management of iTTP.”

Disclosures: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of authors’ disclosures.


Cuker A, Cataland SR, Coppo P, et al. Redefining outcomes in immune TTP: an International Working Group consensus report. Blood. Published online February 2, 2021. doi:10.1182/blood.2020009150