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

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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.

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References

  1. Sarode R, Gottschall JL, Aster RH, McFarland JG (1997) Thrombotic thrombocytopenic purpura: early and late responders. Am J Hematol 54:102–107

    Article  CAS  PubMed  Google Scholar 

  2. Levy GG, Nichols WC, Lian EC, Foroud T, McClintick JN, McGee BM, Yang AY, Siemieniak DR, Stark KR, Gruppo R, Sarode R, Shurin SB, Chandrasekaran V, Stabler SP, Sabio H, Bouhassira EE, Upshaw JD Jr, Ginsburg D, Tsai HM (2001) Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature 413:488–494

    Article  CAS  PubMed  Google Scholar 

  3. Furlan M, Robles R, Galbusera M, Remuzzi G, Kyrle PA, Brenner B, Krause M, Scharrer I, Aumann V, Mittler U, Solenthaler M, Lammle B (1998) von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med 339:1578–1584

    Article  CAS  PubMed  Google Scholar 

  4. Sayani FA, Abrams CS (2015) How I treat refractory thrombotic thrombocytopenic purpura. Blood 125(25):3860–3867

    Article  CAS  PubMed  Google Scholar 

  5. Prescott LF, Park J, Ballantyne A, Adriaenssens P, Proudfoot AT (1977) Treatment of paracetamol (acetaminophen) poisoning with N-acetylcysteine. Lancet 2:432–434

    Article  CAS  PubMed  Google Scholar 

  6. Chen J, Reheman A, Gushiken FC, Nolasco L, Fu X, Moake JL, Ni H, Lopez JA (2011) N-acetylcysteine reduces the size and activity of von Willebrand factor in human plasma and mice. J Clin Invest 121:593–603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Li GW, Rambally S, Kamboj J, Reilly S, Moake JL, Udden MM, Mims MP (2014) Treatment of refractory thrombotic thrombocytopenic purpura with N-acetylcysteine: a case report. Transfusion 54:1221–1224

    Article  CAS  PubMed  Google Scholar 

  8. Shortt J, Oh DH, Opat SS (2013) ADAMTS13 antibody depletion by bortezomib in thrombotic thrombocytopenic purpura. N Engl J Med 368:90–92

    Article  CAS  PubMed  Google Scholar 

  9. Chapin J, Weksler B, Magro C, Laurence J (2012) Eculizumab in the treatment of refractory idiopathic thrombotic thrombocytopenic purpura. Br J Haematol 157:772–774

    Article  CAS  PubMed  Google Scholar 

  10. George JN, Al-Nouri ZL (2012) Diagnostic and therapeutic challenges in the thrombotic thrombocytopenic purpura and hemolytic uremic syndromes. Hematology Am Soc Hematol Educ Program 2012:604–609

    PubMed  Google Scholar 

  11. Rock GA, Shumak KH, Buskard NA, Blanchette VS, Kelton JG, Nair RC, Spasoff RA (1991) Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N Engl J Med 325:393–397

    Article  CAS  PubMed  Google Scholar 

  12. George JN (2010) How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood 116:4060–4069

    Article  CAS  PubMed  Google Scholar 

  13. Anfossi G, Russo I, Massucco P, Mattiello L, Cavalot F, Trovati M (2001) N-acetyl-l-cysteine exerts direct anti-aggregating effect on human platelets. Eur J Clin Invest 31:452–461

    Article  CAS  PubMed  Google Scholar 

  14. Tun NM, Villani GM (2012) Efficacy of rituximab in acute refractory or chronic relapsing non-familial idiopathic thrombotic thrombocytopenic purpura: a systematic review with pooled data analysis. J Thromb Thrombolysis 34:347–359

    Article  CAS  PubMed  Google Scholar 

  15. Ferrara F, Copia C, Annunziata M, Spasiano A, Di Grazia C, Palmieri S, Prossomariti L, Mele G (1999) Vincristine as salvage treatment for refractory thrombotic thrombocytopenic purpura. Ann Hematol 78:521–523

    Article  CAS  PubMed  Google Scholar 

  16. Shortt J, Opat SS, Wood EM (2014) N-Acetylcysteine for thrombotic thrombocytopenic purpura: is a von Willebrand factor-inhibitory dose feasible in vivo? Transfusion 54:2362–2363

    Article  CAS  PubMed  Google Scholar 

  17. Cumberland Pharmaceuticals, Inc. Acetadote (acetylcysteine) injection. Package insert 2013

  18. Wijeysundera DN, Karkouti K, Rao V, Granton JT, Chan CT, Raban R, Carroll J, Poonawala H, Beattie WS (2009) N-acetylcysteine is associated with increased blood loss and blood product utilization during cardiac surgery. Crit Care Med 37:1929–1934

    Article  CAS  PubMed  Google Scholar 

  19. Niemi TT, Munsterhjelm E, Poyhia R, Hynninen MS, Salmenpera MT (2006) The effect of N-acetylcysteine on blood coagulation and platelet function in patients undergoing open repair of abdominal aortic aneurysm. Blood Coagul Fibrinolysis 17:29–34

    Article  CAS  PubMed  Google Scholar 

  20. Knudsen TT, Thorsen S, Jensen SA, Dalhoff K, Schmidt LE, Becker U, Bendtsen F (2005) Effect of intravenous N-acetylcysteine infusion on haemostatic parameters in healthy subjects. Gut 54:515–521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Jepsen S, Hansen AB (1994) The influence of N-acetylcysteine on the measurement of prothrombin time and activated partial thromboplastin time in healthy subjects. Scand J Clin Lab Invest 54:543–547

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to thank the technicians of the plasmapheresis unit for their dedicated help in treating these complicated patients.

Author contributions

A. Rottenstreich, S. Hochberg-Klein, D. Rund and Y. Kalish, designed the study, analyzed the data and wrote the manuscript. All authors approved the final manuscript as submitted.

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    Authors and Affiliations

    1. Hematology Department, Hadassah-Hebrew University Medical Center, 91120, Jerusalem, Israel

      Amihai Rottenstreich, Sarit Hochberg-Klein, Deborah Rund & Yosef Kalish

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    1. Amihai Rottenstreich
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    2. Sarit Hochberg-Klein
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    3. Deborah Rund
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    4. Yosef Kalish
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    Correspondence to Yosef Kalish.

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    The authors declare that they have no conflict of interest.

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    Institutional Review Board approval waiving informed consent was obtained for this study.

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    Amihai Rottenstreich and Sarit Hochberg-Klein have contributed equally to this paper.

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    Rottenstreich, A., Hochberg-Klein, S., Rund, D. et al. The role of N-acetylcysteine in the treatment of thrombotic thrombocytopenic purpura. J Thromb Thrombolysis 41, 678–683 (2016). https://doi.org/10.1007/s11239-015-1259-6

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    • DOI: https://doi.org/10.1007/s11239-015-1259-6

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