Akut Promyelositik Lösemili Çocuk Hastada All-Trans-Retinoik Asit Tedavisiyle İlişkili İntrakardiyak Tromboz

Abstract

Ölümcül koagulopatiler ve hemorajiler akut promiyelositik lösemide (APL) indüksiyon tedavisine yanıt alınamamasının temel sebeplerini oluşturmaktadır. Ağır trombotik olaylar genellikle tanı sırasında ya da tedavinin kilit noktasını oluşturan all-trans-retinoik asit (ATRA) ile remisyon indüksiyon tedavisine başlanmasından hemen sonra gelişir. Diğer yandan izole sağ ventrikül içi tromboz hayatı tehdit edici bir patoloji olup kanser hastalarında nadir olarak saptanmıştır. Bu çalışmada remisyonda iken sağ ventriküler kardiyak trombüs gelişen dokuz yaşındaki APL olgusu nadir görülmesi nedeniyle sunulmuştur. ATRA’nın yan etkilerinin öneminin gösterilmesi, ölümcül olabilen komplikasyonların vurgulanması amaçlanmıştır. Trombozun sadece diferansiyasyon sendromunu sırasında değil tedavinin her döneminde gelişebileceği akılda tutulmalıdır.

Keywords

• Akut promiyelositik lösemi
• All-Trans-Retinoik Asit
• İntrakardiyak tromboz

Intracardiac Thrombus Associated with All-Trans-Retinoic Acid Treatment in a Child with Acute Promyelocytic Leukemia

Abstract

In acute promyelocytic leukemia (APL) potentially fatal coagulopathy and hemorrhages remain major causes of induction failure. Serious thrombotic events are frequently reported at the diagnosis or following remission induction therapy with all-trans-retinoic acid (ATRA), which is a key point in treatment of APL. On the other hand, isolated right ventricular (RV) thrombus is a life-threatening condition and in cancer patients it has been rarely reported. In this report, we have described a very rare a case of ATRA-related isolated right-sided intracardiac thrombus in a nine-year-old child with APL that developed after achievement of complete remission, during the 4th course of ATRA, which is an unexpected period for ATRA-related thrombotic events. We aimed to emphasize the importance of side effects of ATRA and increase awareness against such life-threatening complications. Thrombosis mustn’t be expected only during differentiation syndrome; it should be kept in mind in every phase of treatment with ATRA.

Keywords

• Acute promyelocytic leukemia
• All-trans-retinoic acid
• Intracardiac thrombus

References

1. 1. Ryan MM. Acute promyelocytic leukemia:A summary. J Adv Pract Oncol 2018; 9(2):178-87.
2. 2. Choudhry A, DelLoughery TG. Bleeding and thrombosis in acute promyelocytic leukemia. Am J Hematol 2012; 87(6):596-603.
3. 3. Mitrovic M, Suvajdzic N, Elezovic I, Bogdanovic A, Djordjevic V, Miljic P et al. Prothrombotic events in acute promyelocytic leukemia. Thrombosis Research 2015;135(4);588-93.
4. 4. Ballo P, Fibbi V, Granelli M, Fusco F, Abbondanti A, Fantini A et al. Giant isolated intracardiac thrombus presenting as acute heart failure secondary to right ventricular outflow tract obstruction in a patient with renal carcinoma. Oxf Med Case Reports 2018;6,183-6.
5. 5. De Stefano V, Sora F, Rossi E, Chiusolo P, Laurenti L, Fianchi L et al. The risk of thrombosis in patients with acute leukemia: occurrence of thrombosis at diagnosis and during treatment. J Thromb Haemost 2005;3(9):1985-92.
6. 6. De-Medeiros BC, Strapasson E, Pasquini R, De-Medeiros CR. Effect of all-trans retinoic acid on newly diagnosed acute promyelocytic leukemia patients: results of a Brazilian center. Braz J Med Biol Res 1998;31(12):1537-43.
7. 7. Escudier SM, Kantarjian HM, Estey EH. Thrombosis in patients with acute promyelocytic leukemia treated with and without alltransretinoic acid. Leuk lymphoma 1996;20(5):435-9.
8. 8. Breccia M, Avvisati G, Latagliata R, Carmosino I, Guarini A, De Propris MS et al. Occurrence of thrombotic events in acute promyelocytic leukemia correlates with consistent immunophenotypic and molecular features. Leukemia 2007;21(5-6):79-83.

9. 9. Rashidi A, Silverberg ML, Conkling PR, Fisher SI.Thrombosis in acute promyelocytic leukemia.Thrombosis Res 2013;131(4):281-9.
10. 10. Makki ABE, Mahtat ME, Kheyi J, Bouzelmat H, Chaib A. A rare case of perimyocarditis induced by all-trans retinoic acid administration during induction treatment of acute promyelocytic leukemia. Med Pharma Reports 2019;92(4):418-20.
11. 11. Chen PZ, Wu YJ, Wu CC, Wang YW. Bradycardia during induction therapy with all-trans retinoic acid in patients with acute promyelocytic leukemia: case report and literature review. Case Rep Hematol. 2018;7:1-6. doi: 10.1155/2018/4938797. eCollection 2018.
12. 12. De D, Nath Uk, Chakrabarti P. Pancreatitis in acute promyelocytic leukemia: Drug-induced or differentiation syndrome? Indian J Med Paediatr Oncol 2017;38(3):371-3.
13. 13. Hateke K, Uwai M, Ohtsuki T, Tomizuka H, Izumi T, Yoshida M et al. Rare but important adverse effects of all-trans retinoic acid in acute promyelocytic leukemia and their management. Int J Hematol 1997;66(1):13-9.
14. 14. Sora F, Chiusolo P, Laurenti L, Autore F, Giammarco S, Sica S. Massive pulmonary embolism at the onset of acute promyelocytic leukemia. Mediterr J Hematol Infect Dis 2016; 8(1);e2016027. doi: 10.4084/MJHID.2016.027
15. 15. Jimenez-Yuste V, Martin MP, Canales M, Ojeda E, Hemandez-Navarro F. Pulmonary embolism in a patient with acute promyelocytic leukemia treated with all-trans retinoic acid. Leukemia 1997;11(11):1988-9.
16. 16. Vaid AK, Batra S, Karanth SS, Gupta S. Acute promyelocytic leukemia presenting as pulmonary thromboembolism: Not all APLs bleed. Avicenna J Med 2015;5(4):131-3.
17. 17. Sanz MA, Montesinos P. Open issues on bleeding and thrombosis in acute promyelocytic leukemia. Thromb Res 2010;125(Suppl. 2):S51-4.
18. 18. Dombret H, Scrobohaci ML, Ghorra P. Coagulation disorders associated with acute promyelocytic leukemia: Corrective effect of all-trans retinoic acid treatment. Leukemia 1993;7(1):2-9.