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

From the Guidelines

Yes, it is possible to have ADAMTS13 activity less than 10% and not have thrombotic thrombocytopenic purpura (TTP). While severe ADAMTS13 deficiency (activity <10%) is a hallmark of TTP, this finding alone is not sufficient for diagnosis. Several other conditions can cause severely reduced ADAMTS13 levels, including severe liver disease, sepsis, disseminated intravascular coagulation (DIC), certain medications, pregnancy complications, and other autoimmune disorders. Additionally, some individuals may have congenital ADAMTS13 deficiency (Upshaw-Schulman syndrome) but remain asymptomatic until triggered by factors like pregnancy, infection, or surgery. The diagnosis of TTP requires clinical correlation with the pentad of thrombocytopenia, microangiopathic hemolytic anemia, neurological symptoms, renal dysfunction, and fever, though not all features need to be present.

When encountering a patient with ADAMTS13 activity below 10%, clinicians should perform a comprehensive evaluation including complete blood count, peripheral blood smear, coagulation studies, and assessment of organ function to distinguish TTP from other conditions that can reduce ADAMTS13 levels. According to the most recent guidelines, such as those from the American Society of Clinical Oncology 1, the management of TTP involves a high index of suspicion for the diagnosis and timely recognition, with immediate hematology consultation and stabilization of any critical organ dysfunction.

Key considerations in the evaluation of a patient with low ADAMTS13 activity include:

• Clinical correlation with the pentad of TTP symptoms
• Complete blood count and peripheral blood smear to assess for thrombocytopenia and microangiopathic hemolytic anemia
• Coagulation studies to evaluate for disseminated intravascular coagulation (DIC)
• Assessment of organ function, including renal function and neurological symptoms
• Consideration of other conditions that can cause reduced ADAMTS13 levels, such as severe liver disease, sepsis, and autoimmune disorders.

In the context of immune-related adverse events, the management of TTP may involve holding immune checkpoint inhibitor therapy and administering corticosteroids, with or without plasma exchange, depending on the severity of the condition 1. However, the primary consideration should always be the clinical correlation and comprehensive evaluation of the patient, rather than relying solely on ADAMTS13 activity levels.

From the Research

ADAMTS13 Deficiency and TTP

• ADAMTS13 deficiency is a characteristic of thrombotic thrombocytopenic purpura (TTP), but it is not the only factor that determines the disease 2.
• Studies have shown that patients with severe ADAMTS13 deficiency (activity ≤10%) are more likely to be diagnosed with autoimmune TTP 3.
• However, having an ADAMTS13 activity level less than 10% does not necessarily mean that a patient will develop TTP, as other factors may contribute to the disease 2.

Predictive Value of ADAMTS13 Deficiency

• The predictive value of ADAMTS13 deficiency for TTP is not absolute, and other thrombocytopenic disorders may also present with low ADAMTS13 activity levels 2.
• A study found that some patients with idiopathic thrombocytopenic purpura, acute leukemia, and sepsis also had severely deficient ADAMTS13 activity, although not all patients with these conditions had low ADAMTS13 levels 2.
• Another study suggested that the combination of low ADAMTS13 activity and high anti-ADAMTS13 antibodies during remission may predict disease relapse in patients with immune-mediated TTP 4.

Clinical Implications

• The presence of severe ADAMTS13 deficiency is a strong indicator of autoimmune TTP, but it is not a guarantee of the disease 3.
• Patients with ADAMTS13 activity less than 10% may not necessarily develop TTP, and other factors should be considered in the diagnosis and management of the disease 2.
• Further research is needed to fully understand the relationship between ADAMTS13 deficiency and TTP, as well as the predictive value of ADAMTS13 activity levels in different clinical contexts 5, 6.