A Rare But Fatal Toxicity: Immune Checkpoint Inhibitor-Related Acquired Thrombotic Thrombocytopenic Purpura

Thrombotic thrombocytopenic purpura (TTP) is characterized by thrombotic microangiopathy resulting from decreased activation of the von Willebrand factor-cleaving protease (ADAMTS13). TTP can cause organ damage and is often fatal if the appropriate treatment is not started immediately. Although primary immune TTP is the most common form of TTP, secondary immune etiologies, including complications from immune checkpoint inhibitors (ICIs), have also been reported. ICIs are used as neoadjuvant and adjuvant therapy for metastatic and nonmetastatic solid tumors and hematologic cancers. ICIs stimulate the T-cell-mediated antitumor response, and the subsequent upregulation of the immune system can cause ICI-related adverse events (AEs). ICI-associated AEs may result in various hematological outcomes. Therefore, TTP, as a rare ICI-related AE, requires awareness. TTP has been mentioned as a rare ICIrAE in a few case reports. When using ICIs, the differential diagnosis of TTP should be considered if hemolytic anemia is accompanied by thrombocytopenia. Low ADAMTS13 activity can be used to diagnose TTP and support the need for plasma exchange. This review will assess the approach for ICI-related acquired TTP by scanning a limited number of reported case series in the literature. Low ADAMTS13 activity can be used to diagnose TTP and support the need for plasma exchange. Treatment in the cases that have been published includes combinations of rituximab and caplacizumab, corticosteroids, and plasma exchange. Furthermore, acquired TTP associated with ICI is encountered during the initial and subsequent cycles of ICI treatment. It is essential to detect ICI-related acquired TTP early, a highly fatal AE of ICIs, and to increase awareness of TTP, which will likely be encountered more frequently with the use of new ICI agents.