Predictors of relapse and preventative strategies in immune thrombotic thrombocytopenic purpura

ABSTRACT

Introduction

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare autoimmune blood disorder, which presents with microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombosis and is caused by severe deficiency of ADAMTS13. iTTP may result in both acute and chronic complications and is rapidly fatal without expedient treatment. Life-time risk of relapse is approximately 40%.

Areas Covered

A number of predictors of relapse has been described in the literature. The most well-studied predictor of relapse is persistent ADAMTS13 deficiency; however, it is not a perfect marker. Relapse can be prevented by treatment with immunosuppressive medications, with rituximab being the most studied.

Expert Opinion

Patients who recover from iTTP should be regularly assessed, including with ADAMTS13 activity testing. The optimal frequency of assessments has not been established, but every 3 months is recommended. Considering the potential for significant organ damage and mortality associated with iTTP relapse, patients in remission and with persistent ADAMTS13 activity of 10–20% should be prophylactically treated with immunosuppression. Additional markers to precisely identify patients at higher risk of relapse are needed.

KEYWORDS:

• Thrombotic thrombocytopenic purpura (TTP)
• relapse
• rituximab
• ADAMTS13

Article highlights

• Approximately 40% of iTTP patients relapse after their initial presentation.

• There are modifiable and non-modifiable predictors of relapse. Modifiable factors include ADAMTS13 activity, antibody, antigen and conformation; prior relapse; and exposure to triggers. Non-modifiable factors include age, sex, and HLA type among others.

• Persistent deficiency of ADAMTS13 activity in remission is the most well-studied predictor of relapse; however, it is an imperfect marker.

• Patients who recover from iTTP should be assessed regularly for chronic complications and risk of relapse, including with regular measurements of ADAMTS13 activity.

• A clinical relapse may be prevented by pre-emptively treating severe ADAMTS13 deficiency with rituximab or other immunosuppressive agents.

Acknowledgments

We gratefully acknowledge Yu Xiang Ren for designing the figure.

Declaration of interest

KP has received honoraria for participation in advisory boards, consulting and speaking from Alexion, Ablynx/Sanofi, and Shire/Takeda, and was involved in industry trials from Ablynx/Sanofi and Shire/Takeda.

SHS Huang has served as a consultant for Alexion.

CJ Patriquin has received honoraria for participation in advisory boards and consulting from Sanofi, Octapharma, Alexion, Apellis/Sobi, and Biocryst.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.