N-acetylcysteine in Thrombotic Thrombocytopenic Purpura: A Systematic Review

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy characterized by severe ADAMTS13 deficiency and accumulation of ultralarge von Willebrand factor multimers. Although therapeutic plasma exchange (PEX), corticosteroids, rituximab, and caplacizumab have improved outcomes, refractory and relapsing disease remain important clinical challenges. N-acetylcysteine (NAC) has been explored as an adjunctive therapy because of its ability to reduce disulfide bonds within von Willebrand factor multimers.

This systematic review aimed to summarize the published clinical experience with NAC in TTP, including treatment strategies, reported outcomes, and safety.

A systematic search of PubMed was performed from database inception until December 31, 2025, using combinations of the terms "thrombotic thrombocytopenic purpura", "TTP", "N-acetylcysteine", and "acetylcysteine". Two reviewers independently screened records, assessed full texts against predefined eligibility criteria, and extracted study-level data. Eligible studies included case reports and case series describing therapeutic NAC use in patients with TTP. The review was conducted in accordance with PRISMA 2020 guidance. The protocol was not prospectively registered.

Six publications comprising 22 adult patients were included. NAC was used as adjunctive therapy, predominantly in refractory or relapsing TTP, alongside PEX, corticosteroids, rituximab, and/or other immunosuppressive therapies. Platelet recovery was reported following NAC initiation in the included cases, with concurrent improvement in hemolysis markers and neurologic symptoms described in some reports. No serious NAC-related adverse events were reported in the included cases. Because all evidence was derived from uncontrolled reports with concomitant therapies, the independent contribution of NAC cannot be established.

The available case-based literature suggests that NAC is a biologically plausible and generally well-tolerated adjunctive therapy in refractory or relapsing TTP. However, the current evidence remains hypothesis-generating and is insufficient to establish efficacy. Prospective studies are needed to clarify its therapeutic role, optimal dosing, and patient selection.