The role of N-acetylcysteine in the treatment of thrombotic thrombocytopenic purpura

Abstract

Thrombotic thrombocytopenic purpura (TTP) is an acute, thrombotic microangiopathy with a high mortality rate if left untreated. Plasma exchange (PEX) is the current standard of care. However, a significant number of patients are refractory to this treatment. N-acetylcysteine (NAC) was recently suggested as a potential therapeutic adjunct for patients with TTP. This study reports a series of three patients with TTP successfully treated with NAC in addition to standard therapy. Detailed chart reviews on these patients were conducted. We discuss clinical features, laboratory findings and management of three patients who presented with microangiopathic hemolytic anemia and thrombocytopenia. Anti-ADAMTS13 antibodies and low levels of ADAMTS13 were detected and confirmed the diagnosis of acquired TTP. Based upon their severe presentation or lack of response to initial treatment with PEX, corticosteroids and other immunosuppressive agents, NAC was added. Under this combined treatment, all three patients hada significant clinical improvement of symptoms with concurrent normalization of platelet count and ADAMTS13 activity level. This report highlights the potential therapeutic utility of NAC in the treatment of TTP. Randomized controlled studies will be required to better characterize the risk-to-benefit ratio of NAC in the treatment of TTP.

Molecular suitability of the chacma baboon in human‐targeted Von Willebrand factor directed studies

“…3 The human VWF gene is translated into a 2813 amino acid preproprotein. 4 The size of the VWF gene, together with the presence of a pseudogene on chromosome 22, which corresponds to 97% of the VWF gene's exons [23][24][25][26][27][28][29][30][31][32][33][34], makes sequencing of the whole VWF gene more complex. 5 The VWF protein contains distinct domains that are arranged as follows: SP-D1-D2-D'-D3-A1-A2-A3-D4-C1-C2-C3-C4-C5-C6-CK.…”

“…23 It was in contrast to very promising results reported in the human clinical setting, where NAC was effective in treating TTP. [24][25][26] The discrepancy once again opens up the question of translatability of pre-clinical animal model results to the human clinical setting. Therefore, with the link between genotype and drug response becoming all the more relevant, 27 it is imperative to determine the molecular characteristics of pre-clinical animals models, to improve the predictability of these results.…”

Novel therapies in thrombotic thrombocytopenic purpura

“…However, NAC as a single therapy, was unable to reverse TTP signs nor dissolve preexisting VWF-rich thrombi. 32 Case reports have shown successful use of NAC in patients with refractory TTP as evidenced by normalization of platelet function and ADAMTS13 activity in four patients 33,34 but was unsuccessful in three others. [35][36][37] A pilot study to evaluate the use of NAC in suspected TTP is underway (NCT01808521).…”

Egészségügyi szakmai irányelv – A thromboticus thrombocytopeniás purpura (TTP) és a haemolyticus uraemiás syndroma (HUS) kezeléséről

“…N-acetilcisztein (NAC) [58] In vitro csökkenti a szolubilis VWF-multimerek számát és lebontja az ULVWF-t a mucinnal mutatott szerkezeti hasonlóságuknak köszönhetően. Kiegészítő kezelésként jönne elsősorban szóba, de nagyon kevés még a tapasztalat.…”