Evaluation Of Clinical, Laboratory and Treatment Results Of Our Patients With Thrombotic Thrombocytopenic Purpura.

Year 2024, Volume: 46 Issue: 2, 241 - 251, 18.03.2024

Selin Meşeli Hava Üsküdar Teke Neslihan Andıc Eren Gunduz

https://doi.org/10.20515/otd.1343991

Abstract

Thrombotic thrombocytopenic purpura (TTP) is clinically caused by severely deficient activity of the ADAMTS-13 protease. The classical pentad of TTP, microangiopathic hemolytic anemia (MAHA), is thrombocytopenia, neurologic findings, fever, and renal failure. Plasma exchange (PEX), corticosteroids, rituximab are used in the treatment and in recent years, caplasizumab has been included in the treatment combination. The aim of our study is to contribute to the literature by reaching the real-life data of TTP disease, which has between 3.7 and 11 new cases per million, and by determining the results and comparing them with the studies of real-life data in the literature. In our study, clinical and laboratory findings and treatment results of 31 patients who were diagnosed with immune (i) TTP when they were 18 years of age or older between 1.Jan.2008 and 1.Jan.2023 in hospital. Department of Internal Medicine, Department of Hematology were evaluated retrospectively. Of 31 patients, 7 (22.6%) were male. The mean age of the patients at the time of diagnosis was 45.13 ±19.07 (16-83) years. MAHA and thrombocytopenia were detected in all patients. In the treatment, PEX was applied to all patients. The time to start PEX after admission to the hospital was 24 (12-24) hours. While 16 (57.1%) of the patients did not show resistance, 12 (42.9%) patients had resistance. In case of resistance, 4 doses of 375 mg/m2/week rituximab treatment were given to 10 (83.3%) of the patients. As a result of the evaluation made between 12 refractory patients (42.9%) and 16 non-refractory patients (57.7%), a significant difference was found between total bilirubin (p=0.019) and direct bilirubin (p=0.031) values at the time of diagnosis. As a result of the evaluation between 7 mortal patients (22.6%) and 24 non-mortal patients (77.4%), a difference was found in terms of age at the time of diagnosis (p=0.034). In conclusion, TTP is seen more frequently in women than in men, and MAHA thrombocytopenia is an indispensable finding in the diagnosis, and comprehensive analysis of the data is required for diagnosis. The plasma ADisintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13 (ADAMTS-13) activity test is helpful in confirming the diagnosis. PEX is the basis of TTP treatment.

Keywords

Thrombotic thrombocytopenic purpura, therapeutic plasma exchange, hemolysis

Project Number

yok

Trombotik trombositopenik Purpura Tanılı Hastalarımızın Klinik, Laboratuvar ve Tedavi Sonuçlarının Değerlendirilmesi

Abstract

Trombotik trombositopenik purpura (TTP) klinik olarak ADAMTS-13 proteazının eksik aktivitesinden kaynaklanır. TTP’nin klasik pentadı mikroanjiyopatik hemolitik anemi (MAHA), trombositopeni, nörolojik bulgular, ateş ve böbrek yetmezliğidir. Tedavide plazma değişimi (PD), kortikosteroidler, rituksimab kullanılmakta ve son yıllarda kaplasizumab tedavi kombinasyonunda yer almaktadır. Çalışmamızın amacı yılda milyonda 3,7 ile 11 arasında yeni vakanın görüldüğü TTP hastalığına ait gerçek yaşam verilerine ulaşıp sonuçları tespit ederek literatürdeki az sayıdaki gerçek yaşam verilerine ait çalışmalar ile karşılaştırıp literatüre katkı sağlamaktır. Çalışmamızda hastanemizin İç Hastalıkları ABD, Hematoloji BD’da 1.Ocak.2008-1.Ocak.2023 tarihleri arasında 18 yaş ve üzerinde iken immün (i) TTP tanısı konulan 31 hastanın klinik ve laboratuvar bulguları ile tedavi sonuçları retrospektif olarak değerlendirildi. 31 hastanın 7’si erkek (%22,6) idi. Ortalama yaş 45,13 ±19,07 (16-83) yıl idi. Hastaların tamamında MAHA ve trombositopeni tespit edildi. Tedavide tüm hastalara PD uygulandı. Hastaneye başvurudan sonra PD’ye başlama süresi 24 (12-24) saat idi. Hastaların 16’sında (%57,1) 1.basamak tedaviye direnç görülmezken 12’sinde (%42,9) direnç mevcuttu. Direnç durumunda hastaların 10’una (%83,3) 4 doz 375 mg/m2/hafta rituksimab tedavisi verildi. Refrakter 12 hasta (%42,9) ile non-refrakter 16 hasta (%57,7) arasında yapılan değerlendirme sonucunda tanı anındaki total bilirubin (p=0.019) ve direkt bilirubin (p=0.031) değerleri arasında anlamlı fark saptandı. Mortal 7 hasta (%22,6) ile mortal seyretmeyen 24 hasta (%77,4) arasındaki değerlendirme sonucunda tanı anındaki yaş açısından anlamlı fark saptandı (p=0.034). Sonuç olarak TTP’nin kadınlarda erkeklere göre daha sık izlendiği MAHA ile trombositopeninin tanıda olmazsa olmaz bulgular olduğu; tanı için verilerin kapsamlı analizinin gerektiği saptandı. Plazma ADisintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13 (ADAMTS-13) aktivite testi tanının doğrulanmasında yardımcı olup TTP tedavisinin köşe taşını PD oluşturmaktadır.

Keywords

Trombotik trombositopenik purpura, terapötik plazma değişimi, hemoliz

Supporting Institution

yok

Project Number

yok

References

• 1. THD, Trombotik Trombositopenik Purpura Tanı Ve Tedavi Kılavuzu. Ağustos 2021
• 2. Rock GA, Shumak KH, Buskard NA, et al: Comparison of plasma exchange with plasma Infusion In the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N Engl J Med 1991; 325:393 -397.
• 3. Mannucci PM, Peyvandi F. TTP and ADAMTS13: When Is Testing Appropriate?Hematology Am Soc Hematol Educ Program. 2007:121-6.
• 4. Brain Mc, Dacie Jv, Hourıhane Do. Microangiopathic haemolytic anaemia: the possible role of vascular lesions in pathogenesis. Br J Haematol. 1962 Oct:8:358-74.
• 5. George JN, Nester CM. Syndromes of thrombotic microangiopathyN Engl J Med 2014; 371:654.
• 6. Nguyen TC, Liu A, Liu L, et al. Acquired ADAMTS-13 deficiency in pediatric patients with severe sepsis. Haematologica. 2007 Jan;92(1):121-4.
• 7. Feldman JD, Mardiney MR, Unanue ER, et al. The vascular pathology of thrombotic thrombocytopenic purpura. An immunohistochemical and ultrastructural study. Lab Invest 1966;15:927-946.
• 8. Shamseddine A, Chehal A, Usta I, et al. Thrombotic thrombocytopenic purpura and pregnancy: report of four cases and literature review. J Clin Apher 2004;19:5–10.
• 9. Reese JA, Muthurajah DS, Kremer Hovinga JA, et al. Children and adults with thrombotic thrombocytopenic purpura associated with severe, acquired Adamts13 deficiency: comparison of incidence, demographic and clinical features. Pediatr Blood Cancer. 2013 Oct;60(10):1676-82.
• 10. Zhou X, Ye X, Ren Y, et al. Diagnosis and management of acquired thrombotic thrombocytopenic purpura in southeast China: a single center experience of 60 cases. Frontiers of Medicine. 2016;10(4):430-6.
• 11. Sagheer S, Moiz B, Usman M, et al. Retrospective Review of 25 Cases of Thrombotic Thrombocytopenic Purpura in Pakistan: Retrospective Review of TTP. Therapeutic Apheresis and Dialysis. 2012;16(1):97-103.
• 12. Bell WR, Braine HG, Ness PM, et al. Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 patients. N Eng J Med 1991; 325:398.
• 13. Page EE, Kremer Hovinga JA, Terrell DR, et al. Clinical importance of ADAMTS13 activity during remission in patients with acquired thrombotic thrombocytopenic purpura. Blood. 2016 Oct 27;128(17):2175-2178.
• 14. Page EE, Kremer Hovinga JA, Terrell DR, et al. Thrombotic thrombocytopenic purpura: diagnostic criteria, clinical features, and long-term outcomes from 1995 through 2015. Blood Adv. 2017 Apr 6;1(10):590-600.
• 15. Moake JL. Thrombotic microangiopathies. N Engl J Med. 2002 Aug 22;347(8):589-600.
• 16. Bugarin-Estrada E, Gómez-De León A, López-García YK, et al. Clinical presentation in thrombotic thrombocytopenic purpura: Real-world data from two Mexican institutions. J Clin Apher. 2018;33(6):645-53.
• 17. Sayani FA, Abrams CS. How I treat refractory thrombotic thrombocytopenic purpura. Blood. 2015 Jun 18;125(25):3860-7.
• 18. Çeneli O, Yılmaz S, Karaselek MA, et al. Outcome of Thrombotic Thrombocytopenic Purpura Patients: A Single-Center Experience. Turk J Haematol. 2019 Aug 2;36(3):214-215.
• 19. McCrae KR, Sadler JE, Cines D. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. In: Hoffman R, Benz Jr EJ, Shattil SJ, Furie B, Cohen HJ, Silberstein LE, McGlave P, editors. Hematology: basic principles and practice: part: VIII, CH:132. Philadelphia: Elsevier Chuchill Livingstone. p. 2287–304.
• 20. Korkmaz S, Keklik M, Sivgin S, et al. Therapeutic plasma exchange in patients with thrombotic thrombocytopenic purpura: A retrospective multicenter study. Transfusion and Apheresis Science. 2013;48(3):353-8.
• 21. Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020 Oct;18(10):2486-2495.
• 22. Blombery P, Scully M. Management of thrombotic thrombocytopenic purpura: current perspectives. J Blood Med. 2014 Feb 5;5:15-23.
• 23. Patient M, Fuseau P, Deligny C. Thrombotic thrombocytopenia purpura in Martinique: Retrospective study between 2008 and 2015. Rev Med Interne. 2017 Aug;38(8):508-512.
• 24. Yang CW, Chen YC, Dunn P, et al. Thrombotic thrombocytopenic purpura: initial treatment with plasma exchange plus steroids and immunosuppressive agents for relapsing cases. Renal Fail 2003;25:21–30.
• 25. Altuntas F, Aydogdu I, Kabukcu S, et al. Therapeutic plasma exchange for the treatment of thrombotic thrombocytopenic purpura: a retrospective multicenter study. Transfus Apher Sci 2007 Feb;36(1):57–67.
• 26. Zheng XL, Vesely SK, Cataland SR et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020 Oct;18(10):2496-2502.
• 27. Scully M, Yarranton H, Liesner R, et al. Regional UK TTP registry: correlation with laboratory ADAMTS 13 analysis and clinical features. Br J Haematol 2008; 142(5): 819–826.
• 28. Goel R, Ness PM, Takemoto CM, et al. Platelet transfusions in platelet consumptive disorders are associated with arterial thrombosis and in-hospital mortality.. Blood. 2015 Feb 26;125(9):1470-6.
• 29. Swisher KK, Terrell DR, Vesely SK, et al Clinical outcomes after platelet transfusions in patients with thrombotic thrombocytopenic purpura. Transfusion. 2009 May;49(5):873-87
• 30. Bentley MJ, Lehman CM, Blaylock RC, et al. The utility of patient characteristics in predicting severe ADAMTS13 deficiency and response to plasma exchange. Transfusion. 2010 Aug;50(8):1654-64