Can a patient with ADAMTS13 (A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13) activity less than 10% avoid Thrombotic Thrombocytopenic Purpura (TTP) relapse?

From the Guidelines

Yes, it is possible to have ADAMTS13 activity less than 10% and not experience a relapse of thrombotic thrombocytopenic purpura (TTP). While the provided evidence primarily focuses on the management of lupus nephritis and thrombotic microangiopathy, it highlights the importance of rapid diagnosis and prompt treatment in achieving good outcomes for TMA, including TTP 1. The key to understanding the possibility of low ADAMTS13 activity without TTP relapse lies in recognizing that TTP relapse often requires additional triggering factors beyond just low ADAMTS13 activity.

Some of the main points to consider include:

• TTP relapse typically requires a "second hit" such as infections, pregnancy, or other physiological stressors in addition to low ADAMTS13 activity.
• Patients with acquired TTP may continue to produce autoantibodies against ADAMTS13 during remission, keeping levels low without causing symptoms.
• For congenital TTP patients, their baseline ADAMTS13 activity remains chronically low due to genetic mutations.
• Management for patients with persistently low ADAMTS13 includes regular monitoring, prophylactic plasma exchange or rituximab for those with multiple relapses, and caplacizumab during acute episodes, as suggested by guidelines for managing thrombotic microangiopathies 1.

The threshold for clinical relapse varies between individuals, which explains why some patients remain asymptomatic despite very low enzyme activity levels. Therefore, management should focus on monitoring and preventive measures rather than solely on the ADAMTS13 activity level, considering the overall clinical context and the presence of other risk factors or triggering events 1.

From the FDA Drug Label

In the 6 patients in the CABLIVI group who experienced a recurrence of TTP during the follow-up period (i.e., a relapse defined as recurrent thrombocytopenia after initial recovery of platelet count (platelet count ≥150,000/µL) that required reinitiation of daily plasma exchange, occurring after the 30-day post daily plasma exchange period), ADAMTS13 activity levels were <10% at the end of the study drug treatment, indicating that the underlying immunological disease was still active at the time CABLIVI was stopped. The answer to the question is no, it is not possible to conclude that a patient with ADAMTS13 activity less than 10% will not relapse, as the study found that patients with ADAMTS13 activity levels <10% at the end of the study drug treatment were the ones who experienced a recurrence of TTP during the follow-up period 2.

• Key points:
  • ADAMTS13 activity levels <10% indicate active underlying immunological disease
  • Patients with ADAMTS13 activity levels <10% were the ones who experienced a recurrence of TTP during the follow-up period
  • The study does not provide information on patients with ADAMTS13 activity less than 10% who did not relapse.

From the Research

ADAMTS13 Activity and TTP Relapse

• ADAMTS13 activity less than 10% is a characteristic of thrombotic thrombocytopenic purpura (TTP) 3, 4, 5, 6.
• However, the relationship between ADAMTS13 activity and TTP relapse is complex, and low ADAMTS13 activity during clinical remission is a risk factor for TTP relapse 7.
• A study found that patients with severe ADAMTS13 deficiency (activity ≤10%) had superior overall survival at 360 days compared to those without severe deficiency 6.
• Another study showed that recovery of ADAMTS13 activity to more than 10% within seven sessions of daily plasma exchange treatment is significantly associated with a timely achievement of clinical response 5.

Possibility of No Relapse with ADAMTS13 Activity Less Than 10%

• While there is a correlation between low ADAMTS13 activity and increased risk of TTP relapse, it is possible for patients with ADAMTS13 activity less than 10% to not experience a relapse 7.
• A study found that patients with idiopathic TTP-HUS who had severe ADAMTS13 deficiency (activity <5%) had variable presenting features and clinical outcomes, and some did not experience a relapse 4.
• However, the data suggests that patients with severe ADAMTS13 deficiency are more likely to respond well to therapeutic plasma exchange (TPE) and have a lower risk of mortality 6.

Factors Influencing TTP Relapse

• Younger age and lower ADAMTS13 activity during clinical remission are significantly associated with a higher risk of TTP relapse 7.
• ADAMTS13 antibody IgG levels are not predictive of TTP relapses 7.
• The use of TPE in patients with ADAMTS13 activity >10% varies significantly across institutions, and its impact on mortality is unclear 6.