N-Acetylcysteine Increases Platelet Counts in Patients with Thrombotic Thrombocytopenia Purpura

Thrombotic thrombocytopenic purpura (TTP) is a rare hematologic disorder caused by a deficiency of plasma ADAMST13 and systemic microvascular occlusion from von Willebrand factor (vWF)-platelet thrombi. The standard of care is therapeutic plasma exchange (TPE) therapy – a burdensome treatment for patients.

N-acetylcysteine (NAC) has been proposed as an adjunct treatment for TTP, for its ability to reduce the size and activity of vWF in vitro in human plasma and in vivo in mouse models. However, prior research from two case studies in patients with refractory TTP found varying results, raising questions about its effectiveness in this setting.

A recent clinical and biochemical study examined two patients with relapsed TTP who were treated with NAC. Junmei Chen, PhD, from the BloodworksNW Research Institute in Seattle, Washington, and colleagues discussed the findings at the ASH annual meeting last month.

“NAC treatment of two patients with TTP in conjunction with TPE was well tolerated and associated with recovery of platelet count,” Dr. Chen and colleagues reported, as well as decreases in lactate dehydrogenase (LDH), increased ADAMTS13-specific activity, and reduced platelet activation.

The researchers determined the following before, during, and after NAC treatment:

  • Concentrations of NAC, cysteine, and glutathione in plasma vWF concentration, multimer structure, and function
  • ADAMTS13 concentration and activity
  • Platelet counts and activation status

The study included two female patients with a history of TTP episodes who presented with acute TTP (ADAMTS13 <10%; positive for ADAMTS13 inhibitors; platelet count ≤10,000/uL; LDH >600 IU/L]). Both patients were treated with NAC 150 mg/kg bolus administered over one hour and 150 mg/kg as continuous infusion until the next TPE. The patients received daily TPE until their platelet counts normalized and intravenous NAC during days two through five. Patients were treated until their platelet counts normalized.

The researchers collected and analyzed the patients’ blood daily for eight days.

Platelet counts in both patients started to increase one day after NAC infusion and, notably, continued to increase after discontinuation of NAC and TPE, Dr. Chen and colleagues observed.

In patient one and patient two, the free thiol concentration in plasma increased four- and 59-fold, respectively, after NAC infusion. “This was accompanied by increasing ADAMTS13 specific activity (ADAMTS13 activity/ADAMTS13 antigen),” the authors wrote. “In patient one, the specific activity increased from 127 percent (prior to NAC infusion but after TPE) to 270 percent during NAC infusion; in patient two, the specific activity increased from 56 percent to 86 percent.”

In patient one, the plasma concentration of vWF (measured by vWF multimeric analysis) had decreased and the vWF multimers migrated slightly faster.

NAC also appeared to inhibit platelet activation, the authors noted: Prior to the NAC infusion, the authors noted, both patients had phosphatidylserine greater than 30 percent and P-selectin greater than 15 percent. During NAC treatment, though, those platelets decreased to less than 18 percent and 10 percent, respectively.

“More clinical studies and detailed analyses are required to examine the effects of NAC in TTP patients,” Dr. Chen and colleagues wrote, but the results from these cases add to the evidence that NAC could serve as adjunct therapy for these patients.


Chen J, Özpolat T, Norby C, et al. N-Acetylcysteine treatment in two patients with relapsed thrombotic thrombocytopenic purpura increased ADAMTS13 activity, free thiol concentration in plasma, and inhibited platelet activation. Abstract #239. Presented at the 2015 ASH Annual Meeting, December 6, 2015; Orlando, Florida.