Eltrombopag Kullanan Hastalarda Arteriyel ve Venöz Tromboz Sıklığı ve Predispozan Faktörlerin Değerlendirilmesi

Abstract

Giriş ve Amaç: Eltrombopag, miyelodisplastik sendrom (MDS), immün trombositopeni (ITP) ve aplastik anemi tedavisinde oral yolla kullanılan küçük moleküllü bir trombopoetin reseptör agonistidir. Eltrombopag megakaryosit farklılaşmasını ve proliferasyonunu uyararak trombosit üretimini arttıran bir ajandır. Bununla birlikte, eltrombopag kullanımıyla ilişkili yüksek bir tromboz (venöz ve arteriyel) riski vardır. Bu çalışmadaki amacımız merkezimizde ITP, MDS, Aplastik Anemi tanısı ile takip edilen ve eltrombopag kullanan hastalarda arteriyel, venöz tromboz sıklığını değerlendirmek ve predispozan faktörlerin retrospektif olarak değerlendirilerek literatüre katkıda bulunmaktır. Yöntem ve Gereçler: 2009–2019 yılları arasında ITP, MDS veya aplastik anemi tanısıyla eltrombopag tedavisi alan ≥18 yaş 144 hastanın verileri retrospektif olarak incelendi. Demografik özellikler, eşlik eden hastalıklar, tedavi dozu ve süresi ile tromboembolik olaylar hasta bilgi yönetim sisteminden elde edildi. Tromboz gelişimiyle ilişkili faktörler istatistiksel olarak analiz edildi. Bulgular: Çalışmaya Eltrombopag tedavisi kullanan 144 hasta dahil edildi. Hastaların 66’sı (%45.8) erkek, 78’i (%54.2) kadındı. Hastaların yaş ortalaması 54.12±20.08 yıl olarak saptandı. Hastalardan 102’sinin (%70.8) tanısı ITP, 31’inin (%21.5) tanısı aplastik anemi ve 11 (%7.6) ‘sinin tanısı MDS idi. Takipte ilk tromboembolik olay 7 hastada (%4,9) görüldü (6 venöz, 1 arteriyel). Tüm vasküler olaylar dikkate alındığında (aynı hastada birden fazla olaya izin verilerek) toplam 13 olay kaydedildi: 7 venöz (4 portal ven trombozu, 3 pulmoner emboli) ve 6 arteriyel (1 miyokard enfarktüsü, 5 inme). Tartışma ve Sonuç: Gerçek yaşam kohortumuzda eltrombopag tedavisi, tromboembolik olayların %4,9’luk bir insidansı ile ilişkili bulunmuş olup, özellikle tromboz açısından bilinen risk faktörleri olan hastalarda yakın takip gerekliliğini vurgulamaktadır.

Keywords

• Eltrombopag
• tromboz
• immün trombositopeni
• aplastik anemi
• miyelodisplastik sendrom.

Evaluation of the incidence of arterial and venous thrombosis and predisposing factors in patients using eltrombopag

Abstract

Eltrombopag is a small-molecule thrombopoietin receptor agonist that is taken orally and prescribed for the management of conditions such as immune thrombocytopenia (ITP), aplastic anemia (AA), and myelodysplastic syndromes (MDS). By stimulating megakaryocyte differentiation and proliferation, it increases platelet production. Eltrombopag treatment has been linked to an increased likelihood of developing both arterial and venous thrombotic events. The present study sought to determine the frequency of such thrombotic complications among patients diagnosed with ITP, MDS, or AA who were treated with eltrombopag in our institution and to retrospectively assess potential risk factors, aiming to provide additional real-world clinical insights to the existing literature. The medical files of 144 adult individuals diagnosed with immune thrombocytopenia, myelodysplastic syndrome, or aplastic anemia and treated with eltrombopag between 2009 and 2019 were retrospectively reviewed. Demographics, comorbidities, treatment dose and duration, and thromboembolic events were extracted from the hospital database. Statistical analyses were performed to evaluate factors associated with thrombosis. A total of 144 patients were evaluated in the study, comprising 66 men (45.8%) and 78 women (54.2%), with an average age of 54.12 ± 20.08 years. Diagnoses included ITP in 102 patients (70.8%), AA in 31 (21.5%), and MDS in 11 (7.6%). During follow-up, first thromboembolic events occurred in 7 patients (4.9%): 6 venous and 1 arterial. When all vascular complications were taken into account—allowing for more than one episode per individual—a total of 13 thrombotic events were observed. Of these, 7 were venous in origin (including 4 cases of portal vein thrombosis and 3 cases of pulmonary embolism), while 6 were arterial (comprising 5 cerebrovascular events and 1 myocardial infarction). Within this real-life patient population, eltrombopag use corresponded to a 4.9% rate of thromboembolic complications. In our cohort, no statistically significant association between thrombosis and age, diagnosis, comorbidities, eltrombopag dose, or treatment duration could be demonstrated, most likely because of the limited number of thrombotic events.

Keywords

• Eltrombopag
• Thrombosis
• Immune Thrombocytopenia
• Aplastic Anemia
• Myelodysplastic Syndrome.

References

1. Bussel JB, Cheng G, Saleh MN, et al. Eltrombopag for chronic immune thrombocytopenia. N Engl J Med.2007;357(22):2237-2246.
2. Ghanima W, Godeau B, Cines DB, et al. Long-term safety of thrombopoietin receptor agonists in immune thrombocytopenia. Haematologica. 2021;106(1):123-131.
3. Olnes MJ, Scheinberg P, Calvo KR, et al. Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med. 2012;367(1):11-19.
4. Wong RSM. Transcriptional effects and risks of thrombopoietin receptor agonists. J Hematol Oncol. 2011;4:29.
5. Patel V, Marsh JCW, Mahévas M, et al. Thrombosis with thrombopoietin receptor agonists: a systematic review. Blood Adv. 2018;2(12):1633-1640.
6. Harrison P, Goodall AH. Platelet-derived microparticles and their clinical relevance. Platelets. 2016;27(7):605-606.
7. Rodeghiero F, Ruggeri M. Thrombopoietin receptor agonists and thrombosis risk. Haematologica. 2022;107(3):513- 515.
8. Sun H, Kim NH, Ahn SH, et al. Iron metabolism and mitochondrial dysfunction associated with eltrombopag toxicity. Blood. 2015;125(6):1173-1182.

9. Gonzalez-Porras JR, Godeau B, Carpenedo M, et al. Real-world data on thrombosis in patients treated with eltrombopag. Platelets. 2019;30(3):290-296.
10. Provan D, Arnold DM, Bussel JB, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019;3(22):3780-3817.
11. Cheng G, Saleh MN, Marcher C, et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet. 2011;377(9763):393-402.
12. Saleh MN, Bussel JB, Cheng G, et al; EXTEND Study Group. Safety and efficacy of eltrombopag for treatment of chronic immune thrombocytopenia: results of the long-term, open-label EXTEND study. Blood. 2013;121(3):537-545.
13. Catalá-López F, Corrales I, de la Fuente-Honrubia C, et al. Risk of thromboembolism with thrombopoietin receptor agonists in adult patients with thrombocytopenia: systematic review and meta-analysis of randomized controlled trials. Med Clin (Barc). 2012;139(9):421-429.
14. Dong Y, Xia Z, Zhou J, Hu Y, Yue M, Wang Y, et al. Risk of thrombotic events in immune thrombocytopenia patients treated with thrombopoietic agents: a systematic review and meta-analysis. Thromb J. 2023;21:5. doi: 10.1186/s12959-023-00509-z.
15. Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190-4207.
16. Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829-3866.
17. Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113(11):2386-2393.
18. Severinsen MT, Engebjerg MC, Farkas DK, et al. Risk of venous thromboembolism in patients with primary chronic immune thrombocytopenia: a Danish population-based cohort study. Br J Haematol. 2011;152(3):360-362.
19. Sarpatwari A, Bennett D, Logie JW, et al. Thromboembolic events among adult patients with primary immune thrombocytopenia in the United Kingdom General Practice Research Database. Haematologica. 2010;95(7):1167- 1170.
20. Huang X, Huang Y, Zhang C, Wang Z, Yu L. Relationship between thromboembolic events and thrombopoietin receptor agonists: a pharmacovigilance analysis of the FDA Adverse Event Reporting System and the Japanese Adverse Drug Event Report. BMJ Open. 2025;15:e099153. doi: 10.1136/bmjopen-2025-099153.
21. Qu H, Wu J, Qiaolongbatu C, Song X, Feng T, Wu Z, et al. Safety profile of eltrombopag in different age groups: an analysis of real-world pharmacovigilance and randomized clinical trials. Clin Pharmacol Ther. 2023;114(1):000– 000. doi: 10.1002/cpt.2918.
22. Gangat N, Patnaik MM, Begna K, et al. Primary myelodysplastic syndromes: the Mayo Clinic experience with 1000 patients. Mayo Clin Proc. 2015;90(12):1623-1638.
23. Buckstein R. Epidemiology, etiology, and clinical presentation of myelodysplastic syndromes. In: Zeidan AM, Gore SD, eds. Diagnosis and Management of Myelodysplastic Syndromes. Cham: Springer; 2020:3-17.
24. Comont T, Meunier M, Cherait A, Santana C, Cluzeau T, Slama B, et al. Eltrombopag for myelodysplastic syndromes or chronic myelomonocytic leukaemia with no excess blasts and thrombocytopenia: a French multicentre real-life study. Br J Haematol. 2021;194(2):e50–e54. doi: 10.1111/bjh.17539.
25. Ecsedi M, Lengline E, Knol-Bout C, et al. Use of eltrombopag in aplastic anemia in Europe: a retrospective study. Ann Hematol. 2019;98(6):1341-1350.
26. Rinder HM, Schuster JE, Rinder CS, et al. Correlation of thrombosis with increased platelet turnover in thrombocytosis. Blood. 1998;91(4):1288-1294.
27. Schafer AI. Essential thrombocythemia and thrombocytosis. In: Lichtman MA, Beutler E, Kipps TJ, et al, eds. Williams Hematology. 7th ed. New York: McGraw-Hill Medical; 2006:1289-1305.