Unbiased plasma proteomics reveals hemolysis during ADAMTS13 relapse in patients with immune TTP

Abstract Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy that is caused by a deficiency of a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS13). Most patients with TTP have immune-mediated TTP (iTTP), for which the loss of activity results from the development of autoantibodies directed toward ADAMTS13. Preemptive treatment of iTTP with rituximab when ADAMTS13 activity drops to ∼20% (ie, an “ADAMTS13 relapse”) can effectively prevent clinical relapse. Nevertheless, patients still undergo prolonged periods of low ADAMTS13 activity. We used unbiased mass spectrometry–based plasma profiling to study alterations in protein levels in a cohort of patients with iTTP treated with elective rituximab. Protein levels in samples obtained during an ADAMTS13 relapse, after the recovery of ADAMTS13 activity, during follow-up in remission, and during a subsequent ADAMTS13 relapse were measured. When comparing the plasma profiles of all patients during ADAMTS13 relapse and remission, signatures associated with the upregulation of hemolysis and platelet activation were observed. These findings show that biological pathways linked to the onset of acute TTP are upregulated in patients with iTTP with ADAMTS13 deficiency before any clinical or routine biochemical changes are observed.