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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.
Reference
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.

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