A Pilot Study of N-acetylcysteine in Thrombotic Thrombocytopenia Purpura

Thrombotic thrombocytopenic purpura (TTP) is a rare hemostatic disorder with life threatening consequences secondary to microvascular thrombosis. While the use of therapeutic plasma exchange (TPE) has greatly improved survival, end organ damage, resistance to therapy, and relapses occur in many patients. Ultra-large von Willebrand factor multimers (ULVWF) are pathogenic in TTP. The investigators have found that N-acetylcysteine (NAC) cleaves ULVWF in vitro and in vivo in the ADAMTS13 deficient mice that are at increased risk of TTP. NAC is well tolerated in humans at intravenous doses used for treatment of acetaminophen overdose. This dosage correlates with that producing an effect in the murine studies noted above, and thus is an attractive treatment for patients with TTP. By cleaving VWF and preventing propagation of platelet/VWF strings, the investigators hypothesize that NAC treatment will decrease complications in patients with TTP receiving treatment with TPE. This will be manifest by a more rapid improvement in platelet count, decrease in number of days requiring plasma exchange, and decrease in microvascular thrombotic complications. To prepare for a larger trial the investigators propose a pilot study in 3 patients with suspected TTP at the University of Washington (UW) Medical Center. The study will be approved by the UW IRB prior to study initiation. Patients who consent to the study will receive daily NAC infusions beginning after the first TPE, in doses used for acetaminophen overdose. Blood samples will be collected for laboratory assays to determine optimal timing for sample collection in the larger multicenter trial, and to pilot the data collection forms. The investigators will also evaluate safety and patient tolerability.