Can a patient have ADAMTS13 (A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13) activity less than 10% and not develop Thrombotic Thrombocytopenic Purpura (TTP)?

From the Guidelines

Yes, it is possible to have ADAMTS13 activity less than 10% and not develop thrombotic thrombocytopenic purpura (TTP). This situation can occur in several clinical scenarios, as outlined in the KDIGO 2024 clinical practice guideline for the management of lupus nephritis 1. According to the guideline, patients with lupus nephritis and suspected thrombotic microangiopathy should be tested for ADAMTS13 activity and antibodies to ADAMTS13, and management should be based on the underlying etiology of thrombotic microangiopathy.

Key Points to Consider

• Low ADAMTS13 activity (<10%) can be seen in various conditions, including systemic lupus erythematosus-associated thrombotic thrombocytopenic purpura, primary or secondary complement-mediated thrombotic microangiopathy, and other etiologies 1.
• The development of TTP likely requires additional "second hits" beyond just low ADAMTS13 activity, such as endothelial injury or other inflammatory triggers.
• Certain conditions like sepsis, disseminated intravascular coagulation (DIC), liver disease, and post-operative states can also cause severely reduced ADAMTS13 activity without TTP manifestation.
• Some medications, including cyclosporine, tacrolimus, and certain chemotherapeutic agents, can reduce ADAMTS13 activity without causing TTP.

Clinical Implications

• The presence of low ADAMTS13 activity alone is not sufficient to diagnose TTP, and other clinical and laboratory findings should be considered.
• A comprehensive evaluation, including testing for antiphospholipid antibodies and assessment of the PLASMIC score, is necessary to determine the underlying etiology of thrombotic microangiopathy and guide management 1.
• Treatment should be individualized based on the underlying cause of thrombotic microangiopathy, and may include plasma exchange, glucocorticoids, rituximab, and other therapies.

From the Research

ADAMTS13 Activity and TTP

• ADAMTS13 activity less than 10% is typically associated with thrombotic thrombocytopenic purpura (TTP) 2, 3, 4.
• However, some patients with ADAMTS13 activity less than 10% may not develop TTP, suggesting that other factors may be involved in the development of the disease 5.
• The relationship between ADAMTS13 activity and TTP is complex, and severe deficiency of ADAMTS13 activity does not detect all patients who may be appropriately diagnosed with TTP-HUS and who may respond to plasma exchange treatment 5.

Residual ADAMTS13 Activity

• Recent studies suggest that the amount of residual activity of ADAMTS13 may be a major determinant of the clinical heterogeneity of TTP 3.
• The mechanism underlying severe deficiency of plasma ADAMTS-13 activity in immune thrombotic thrombocytopenic purpura is not entirely associated with low levels of ADAMTS-13 antigen, but rather with antibody-mediated inhibition and accelerated clearance of plasma ADAMTS-13 antigen via immune complexes 6.

Clinical Implications

• The rapid return of ADAMTS13 data is important to make the best use of this information in the diagnosis and treatment of TTP 4.
• Plasma infusion or exchange remains the initial treatment of choice for TTP, but novel therapeutics such as recombinant ADAMTS13 and gene therapy are under development 2.