Esansiyel Trombositemi Hastalarının Geriye Dönük Değerlendirilmesi

Yıl 2025, Cilt: 47 Sayı: 6, 1009 - 1021, 26.09.2025

Meltem Arslan Atik , Şerife Solmaz , Tuğba Çetintepe , Hatice Demet Kiper Ünal , Kemal Aygün , Alev Garip Acar , Eray Arslan

https://doi.org/10.20515/otd.1721592

Öz

Çalışmamızda esansiyel trombositemi (ET) tanılı hastalarda klinik, laboratuvar bulguları, tedavileri ile kanama ve tromboz durumlarını etkileyen faktörleri araştırmayı amaçladık. 2016- 2022 arası ET tanısı alan 270 hasta retrospektif incelendi, yaş ortalaması median 59 (19-92), %64’ü kadındı. Yüksek risk skoruna sahip olan JAK2 mutasyon pozitifliği %59 olup hastaların %39’ unda tromboz geliştiği (p=0.001), %23’ ünde kanama olduğu (p=0.008) saptandı. Ayrıca JAK2 pozitif olan hastaların çoğunun 60 yaş üstü olduğu (p=0.05), daha yüksek oranda miyelofibrozis geliştiği (p=0.007) görüldü. JAK2 mutasyonu pozitif hastaların, tanıda daha yüksek trombosit ve hemoglobin (Hb) değerine sahip olduğu bulundu (p=0.05, p=0.013). Hastalarımızın %33’ünde tanıda tromboz vardı (%89 arteryel ve %11 venöz trombozdu). Trombozu etkileyen risk durumları incelendiğinde; lökositoz, yüksek nötrofil ve Hb değeri ile istatistiksel anlamlılık saptandı (p=0.037, p=0.030, p=0.039). Multivariete analiz yapıldığında ise tromboz ile jak-2 pozitifliği ve lökositozun olması anlamlılığını koruyordu (p=0.022, p=0.006). Hastalarımızdan 217’si sağdı (%80). 10 yıllık sağkalım %75 olup, 60 yaş üstü hastalarda (p=0.001) ve tromboz olan hasta grubunda toplam sağkalım (OS) daha kısaydı (p=0.026). ELN risk skoru yüksek bulunan hastalarda sağkalım istatistiksel olarak anlamlı şekilde düşük saptandı (p=0.001) Revise-İPSET’ e göre orta ve yüksek skora sahip olanlarda sağkalım istatistiksel olarak anlamlı şekilde daha kısa bulundu (p=0.006). ET senelerce asemptomatik seyir gösterebileceği gibi, hayatı tehdit edebilen tromboembolik komplikasyonlar ve hemorajik durumlar ile karşımıza çıkmaktadır. Bu nedenle ET hastalarının yönetimi ve tedavi ihtiyacı olan yüksek riske sahip grubu tespit etmek önem taşımaktadır.

Anahtar Kelimeler

Esansiyel Trombositemi , Kanama , Tromboz , Sağkalım

Retrospective Evaluation of Essential Thrombocythemia Patients

Öz

In our study, we aimed to investigate the clinical and laboratory findings, treatments, and factors affecting bleeding and thrombosis in patients with essential thrombocythemia (ET). A retrospective analysis was performed on 270 patients diagnosed with ET between 2016 and 2022. The median mean age was 59 years (19-92 years), and 64% were female. High-risk JAK2 mutation positivity was found in 59% of patients, and thrombosis developed in 39% of patients (p=0.001), and bleeding occurred in 23% (p=0.008). Furthermore, most JAK2-positive patients were over 60 years of age (p=0.05), and they developed myelofibrosis at a higher rate (p=0.007). JAK2 mutation-positive patients were found to have higher platelet and hemoglobin (Hb) values at diagnosis (p=0.05, p=0.013). Thirty-three percent of our patients had thrombosis at diagnosis (89% were arterial and 11% were venous). When risk factors affecting thrombosis were examined, statistical significance was found with leukocytosis, high neutrophil and Hb values (p=0.037, p=0.030, p=0.039). When multivariate analysis was performed, it was seen that the development of thrombosis and JAK2 positivity and leukocytosis were significantly correlated (p=0.022, p=0.006). 217 of our patients survived (80%). 10-year survival was 75%, and overall survival (OS) was shorter in patients over 60 years of age (p=0.001) and in the group with thrombosis (p=0.026). Survival was found to be statistically significantly shorter in patients with a high ELN risk score (p=0.001). According to Revise-IPSET, survival was found to be statistically significantly shorter in those with moderate and high scores (p=0.006). ET can present with asymptomatic symptoms for years or can present with life-threatening thromboembolic complications and hemorrhagic conditions. Therefore, it is important to manage ET patients and identify high-risk groups requiring treatment.

Anahtar Kelimeler

Essential Thrombocytemia , Bleeding , Thrombosis , ELN , IPSET , Revise-IPSET

Kaynakça

• 1. Hematoloj RK, Trombos YEL. Esansiyel trombositemi. HematoLog. 2012;37–54. https://www.thd.org.tr/thdData/Books/204/esansiyel-trombositemi.pdf Erişim 12.04.2024.
• 2. Srour SA, Devesa SS, Morton LM, Check DP, Curtis RE, Linet MS, et al. Incidence and patient survival of myeloproliferative neoplasms and myelodysplastic/myeloproliferative neoplasms in the United States, 2001–12. Br J Haematol. 2016;174(3):382–96.
• 3. Tefferi A, Barbui T. Polycythemia vera and essential thrombocythemia: 2017 update on diagnosis, risk-stratification, and management. Am J Hematol. 2017;92(1):94–108.
• 4. Karakuş V, Kurtoğlu E. Miyeloproliferatif hastalıkta trombotik olayların patogenezi ve tedavisi. 2016.
• 5. Tefferi A, Barbui T. Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk-stratification and management. Am J Hematol. 2019;94(1):133–43.
• 6. Türkiye Klinikleri Hematoloji. Özel konular. Türkiye Klinikleri Dergiler. 2013;6(1).
• 7. Tefferi A, Guglielmelli P, Larson DR, Finke C, Wassie EA, Pieri L, et al. Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood. 2014;124(16):2507–13.
• 8. Vainchenker W, Kralovics R. Genetic basis and molecular pathophysiology of classical myeloproliferative neoplasms. Blood. 2017;129(6):667–79.
• 9. Vannucchi AM, Guglielmelli P, Tefferi A. Polycythemia vera and essential thrombocythemia: Algorithmic approach. Curr Opin Hematol. 2018;25(2):112–9.
• 10. İstanbul Üniversitesi Tıp Fakültesi. Miyeloproliferatif neoplazilerde moleküler olayların önemi the impact of molecular events on myeloproliferative neoplasms. İstanbul Tıp Fakültesi Derg. 2015.
• 11. Cortelazzo S, Finazzi G, Ruggeri M, Vestri O, Galli M, Rodeghiero F, et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med. 1995;332(17):1132–7.
• 12. Michiels JJ, Van Genderen PJ, Jansen PH, Koudstaal PJ. Atypical transient ischemic attacks in thrombocythemia of various myeloproliferative disorders. Leukemia & Lymphoma. 1996;22(sup1):65–70.
• 13. Vannucchi AM, Guglielmelli P. What are the current treatment approaches for patients with polycythemia vera and essential thrombocythemia? Hematology 2014, the American Society of Hematology Education Program Book. 2017;2017(1):480-8.
• 14. Barbui T, Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, et al. Development and validation of an international prognostic score of thrombosis in world health organization-essential thrombocythemia (IPSET-thrombosis). Blood. 2012;120(26):5128–33.
• 15. Vannucchi AM, Barbui T, Cervantes F, Harrison C, Kiladjian JJ, Kröger N, et al. Philadelphia chromosome-negative chronic myeloproliferative neoplasms: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26:v85–99
• 16. Schafer AI. Thrombocytosis. N Engl J Med. 2004;350(12):1211–9.
• 17. Yazdani Brojeni P, Matok I, Garcia Bournissen F, Koren G. A systematic review of the fetal safety of interferon alpha. Reprod Toxicol. 2012.
• 18. Verstovsek S, Kantarjian H, Mesa RA, Pardanani AD, Cortes-Franco J, Thomas D, Tefferi A. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. New England Journal of Medicine. 2010;363(12):1117–27.
• 19. Vannucchi AM, Barbui T, Cervantes F, Harrison C, Kiladjian JJ, Kröger N, ESMO Guidelines Committee. Philadelphia chromosome-negative chronic myeloproliferative neoplasms: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2015;26(suppl 5):v85–v99.
• 20. Stockklausner C, Duffert CM, Cario H, Knöfler R, Streif W, Kulozik AE. Thrombocytosis in children and adolescents-classification, diagnostic approach, and clinical management. Ann Hematol. 2021;100(7):1647–65.
• 21. Tefferi A. The Philadelphia chromosome negative chronic myeloproliferative disorders: A practical overview. Mayo Clin Proc. 1998;73(12):1177–84.
• 22. Harrison CN. Current trends in essential thrombocythaemia. Br J Haematol. 2002;117(4):796–808.
• 23. McNally RJQ, Rowland D, Roman E, Cartwright RA. Age and sex distributions of hematological malignancies in the U.K. Hematol Oncol. 1997;15(4):173–89.
• 24. Mesa RA, Silverstein MN, Jacobsen SJ, Wollan PC, Tefferi A. Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: An olmsted county study, 1976-1995. Am J Hematol. 1999;61(1):10–5.
• 25. Demir AM, Ümit EG. Esansiyel trombositemi. Türkiye Klinikleri Journal of Hematology Special Topics. 2013;6(2):19-25.
• 26. Tefferi A, Barbui T. Polycytemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management. American Journal of Hematology. 2015;90(2):162-73.
• 27. Acar C, Solmaz Ş, Namdaroglu S, Çetintepe T, Çetintepe L, Mutlu C, et al. Esansiyel trombositoz tanılı hastalarımızın retrospektif değerlendirilmesi. İzmir Eğitim ve Araştırma Hastan Tıp Derg. 2018;22(3):101–4.
• 28. Bilim Merkezi. JAK2 V617F mutasyon durumuna göre esansiyel trombositemi ve polisitemi vera hastalarında tromboz riski. Hematolojik. 92(1):135–6.
• 29. Atilla FD, Şahin F, Saydam G. Yaşlı hastada kronik miyeloid lösemi dışı kronik miyeloproliferatif hastalıklar. Turkiye Klin Hematol Spec Top. 2018;11(3):31–7.
• 30. Lussana F, Caberlon S, Pagani C, Kamphuisen PW, Büller HR, Cattaneo M. Association of V617F Jak2 mutation with the risk of thrombosis among patients with essential thrombocythaemia or idiopathic myelofibrosis: A systematic review. Thrombosis Research. 2009;124(4):409–17.
• 31. Bayram M, Özkocaman V, Özkalemkaş F, Ali̇ R, Karkucak M, Özçeli̇k T, et al. Esansiyel trombositoz tanısıyla izlenen olgularda JAK-2 gen mutasyonu ve komplikasyonlarla ilişkisi. Uludağ Üniversitesi Tıp Fakültesi Derg. 2011;37(1):13–6.
• 32. De Stefano V, Za T, Rossi E, Fiorini A, Ciminello A, Luzzi C, Leone G. Influence of the JAK2 V617F mutation and inherited thrombophilia on the thrombotic risk among patients with essential thrombocythemia. Haematologica. 2009;94(5):733–7.
• 33. Dahabreh IJ, Zoi K, Giannouli S, Zoi C, Loukopoulos D, Voulgarelis M. Is JAK2 V617F mutation more than a diagnostic index? Leukemia Research. 2009;33(1):67–73.
• 34. De Stefano V. Leukocytosis is a risk factor for recurrent arterial thrombosis in young patients with polycythemia vera and essential thrombocythemia. American Journal of Hematology.
• 35. Andriani A, Latagliata R, Anaclerico B, Spadea A, Rago A, Di Veroli A, et al. Spleen enlargement is a risk factor for thrombosis in essential thrombocythemia: Evaluation on 1,297 patients. Am J Hematol. 2016;91(3):318–21.
• 36. Mejía-Ochoa M, Acevedo Toro PA, Cardona-Arias JA. Systematization of analytical studies of polycythemia vera, essential thrombocythemia and primary myelofibrosis, and a meta-analysis of the frequency of JAK2, CALR and MPL mutations: 2000-2018. BMC Cancer. 2019;19(1).
• 37. Abdelghani M, Hammami H, Zidi W, Amouri H, Othmen HBH, Farrah A, et al. Hematological relevance of JAK2 V617F and calreticulin mutations in Tunisian patients with essential thrombocythemia. J Clin Lab Anal. 2022;36(8).
• 38. Bilim Merkezi. İlk on yılın ötesinde esansiyel trombositemi: Yaşam beklentisi, uzun dönem komplikasyon oranları ve prognostik faktörler. Mayo Clinic Proceedings. 81(2):159–66.
• 39. Alvarez-Larrán A, Pereira A, Guglielmelli P, Hernández-Boluda JC, Arellano-Rodrigo E, Ferrer-Marín F, et al. Antiplatelet therapy versus observation in low-risk essential thrombocythemia with a CALR mutation. Haematologica. 2016;101(8):926–31.
• 40. Besses C, Cervantes F, Pereira A, Florensa L, Sole F, Hernandez-Boluda JC, Montserrat E. Major vascular complications in essential thrombocythemia: A study of the predictive factors in a series of 148 patients. Leukemia. 1999;13(2):150–4.
• 41. Tefferi A. Annual clinical updates in hematological malignancies: A continuing medical education series: Polycythemia vera and essential thrombocythemia: 2011 update on diagnosis, risk-stratification, and management. Am J Hematol. 2011;86(3):292–301.
• 42. Chou YS, Gau JP, Yu YB, Pai JT, Hsiao LT, Liu JH, Tzeng CH. Leukocytosis in polycythemia vera and splenomegaly in essential thrombocythemia are independent risk factors for hemorrhage. European Journal of Haematology. 2013;90(3):228–36.
• 43. Vannucchi AM, Guglielmelli P, Tefferi A. Advances in understanding and management of myeloproliferative neoplasms. CA Cancer J Clin. 2009;59(3):171–91.
• 44. Gangat N, Wolanskyj AP, McClure RF, Li CY, Schwager S, Wu W, et al. Risk stratification for survival and leukemic transformation in essential thrombocythemia: A single institutional study of 605 patients. Leukemia. 2007;21(2):270–6.
• 45. Dan K, Yamada T, Kimura Y, Usui N, Okamoto S, Sugihara T, Japanese Elderly Leukemia and Lymphoma Study Group. Clinical features of polycythemia vera and essential thrombocythemia in Japan: Retrospective analysis of a nationwide survey by the Japanese Elderly Leukemia and Lymphoma Study Group. International Journal of Hematology. 2006;83(5):443–9.
• 46. Spencer P, Wang Y. Letters to the editor: To the editor. J Dent Res. 2001;80(5):1400.
• 47. Petrides PE, Gisslinger H, Steurer M, Linkesch W, Krumpl G, Schüller A, et al. Pharmacokinetics, bioequivalence, tolerability, and effects on platelet counts of two formulations of anagrelide in healthy volunteers and patients with thrombocythemia associated with chronic myeloproliferation. Clin Ther. 2009;31(2):386–98.
• 48. Yamaguchi K, Hisano M, Sakata M, Minatogawa Y, Suzuki T, Ozawa N, et al. Periodic plateletpheresis during pregnancy in a high-risk patient with essential thrombocythemia. J Clin Apher. 2006;21(4):256–9.
• 49. Das SS, Bose S, Chatterjee S, Parida AK, Pradhan SK. Thrombocytapheresis: Managing essential thrombocythemia in a surgical patient. Ann Thorac Surg. 2011;92(1).