Blood Parameters in Treatment with Arsenic Trioxide in Acute Promyelocytic Leukemia: A Systematic Review

  • Mehdi Mohammadi Kanesbi Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
  • Lida Jarahi Department of Community Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  • Mohammad Reza Keramati Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Acute promyelocytic leukemia; Arsenic trioxide; All-trans retinoic acid; Chemotherapy; Disseminated intravascular coagulation


Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML). APL is famed with some special blood coagulation disorders such as disseminated intravascular coagulation (DIC). The therapeutic methods of APL contain All Trans Retinoic Acid (ATRA), arsenic trioxide (ATO) or/and chemotherapy. Many studies have been done on APL blood disorders and its treatment. These studies have shown different results. In this systematic article, we tried to review the effect of ATO therapy with or without ATRA and chemotherapy on DIC parameters (D.dimer, Prothrombin Time, Activated Partial Thrombin Time, Platelet count) in APL patients. The result of included studies demonstrated that although ATO can reduce the number of malignant cells in the bone marrow and peripheral blood, it does not have enough potential to attenuate the danger of high score DIC that is usual in APL patients and should be better to be used with other therapeutic methods.



1. De Kouchkovsky I, Abdul-Hay M. Acute myeloid leukemia: a comprehensive review and 2016 update. Blood Cancer J. 2016; 6(7):e441.
2. Li J, Chen P, Sinogeeva N, et al. Arsenic trioxide promotes histone H3 phosphoacetylation at the chromatin of CASPASE-10 in acute promyelocytic leukemia cells. J Biol Chem. 2002; 277(51):49504–10.
3. Melo RA, de Vasconcellos JF, Melo FC, et al. PML-RARalpha fusion gene transcripts and biological features in acute promyelocytic leukemia patients. Clin Lab Haematol. 2006; 28(2):126–9.
4. Chang H, Kuo MC, Shih LY, et al. Clinical bleeding events and laboratory coagulation profiles in acute promyelocytic leukemia. Eur J Haematol. 2012; 88(4):321–8.
5. Coombs CC, Tavakkoli M, Tallman MS. Acute promyelocytic leukemia: where did we start, where are we now, and the future. Blood Cancer J. 2015; 5:e304.
6. Lee HJ, Park HJ, Kim HW, et al. Comparison of laboratory characteristics between acute promyelocytic leukemia and other subtypes of acute myeloid leukemia with disseminated intravascular coagulation. Blood Res. 2013; 48(4):250–3.
7. Xu F, Wang C, Yin C, et al. Analysis of early death in newly diagnosed acute promyelocytic leukemia patients. Medicine (Baltimore). 2017; 96(51):e9324.
8. Shahmarvand N, Oak JS, Cascio MJ, et al. A study of disseminated intravascular coagulation in acute leukemia reveals markedly elevated D-dimer levels are a sensitive indicator of acute promyelocytic leukemia. Int J Lab Hematol. 2017; 39(4):375–383.
9. Vignoli A, Marchetti M, Falanga A. Acute promyelocytic leukemia cell adhesion to vascular endothelium is reduced by heparins. Ann Hematol. 2018; 97(9):1555–62.
10. Jácomo RH, Santana-Lemos BA, Lima AS, et al. Methionine-induced hyperhomocysteinemia reverts fibrinolytic pathway activation in a murine model of acute promyelocytic leukemia. Blood. 2012; 120(1):207–13.
11. Song LX, Lu HY, Chang CK, et al. Cerebral venous and sinus thrombosis in a patient with acute promyelocytic leukemia during all-trans retinoic acid induction treatment. Blood Coagul Fibrinolysis. 2014; 25(7):773–6.
12. Lee HJ, Kim DH, Lee S, et al. Analysis of factors affecting hemorrhagic diathesis and overall survival in patients with acute promyelocytic leukemia. Korean J Intern Med. 2015; 30(6):884–90.
13. Lou Y, Suo S, Tong H, et al. Hypofibrinogenemia as a clue in the presumptive diagnosis of acute promyelocytic leukemia. Leuk Res. 2016; 50:11–16.
14. Cao M, Li T, He Z, et al. Promyelocytic extracellular chromatin exacerbates coagulation and fibrinolysis in acute promyelocytic leukemia. Blood. 2017; 129(13):1855–1864.
15. David S, Mathews V. Mechanisms and management of coagulopathy in acute promyelocytic leukemia. Thromb Res. 2018; 164 Suppl 1:S82–S8.
16. Daver N, Kantarjian H, Marcucci G, et al. Clinical characteristics and outcomes in patients with acute promyelocytic leukaemia and hyperleucocytosis. Br J Haematol. 2015; 168(5):646–53.
17. Wang P, Zhang Y, Yang H, et al. Characteristics of fibrinolytic disorders in acute promyelocytic leukemia. Hematology. 2018; 23(10):756-764.
18. Shen ZX, Shi ZZ, Fang J, et al. All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci U S A. 2004; 101(15):5328–35.
19. Mathews V, George B, Lakshmi KM, et al. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity. Blood. 2006; 107(7):2627–32.
20. Emadi A, Gore SD. Arsenic trioxide - An old drug rediscovered. Blood Rev. 2010; 24(4–5):191–9.
21. Zhang Y, Wu S, Luo D, et al. Addition of Arsenic Trioxide into Induction Regimens Could Not Accelerate Recovery of Abnormality of Coagulation and Fibrinolysis in Patients with Acute Promyelocytic Leukemia. PloS One. 2016; 11(1):e0147545.
22. Hou J, Wang S, Zhang Y, et al. Causes and prognostic factors for early death in patients with acute promyelocytic leukemia treated with single-agent arsenic trioxide. Ann Hematol. 2017; 96(12):2005–2013.
23. Zhu HH, Guo ZP, Jia JS, et al. The impact of oral arsenic and all-trans-retinoic acid on coagulopathy in acute promyelocytic leukemia. Leuk Res. 2018; 65:14–19.
24. Ishitsuka K, Shirahashi A, Iwao Y, et al. Bone marrow necrosis in a patient with acute promyelocytic leukemia during re-induction therapy with arsenic trioxide. Eur J Haematol. 2004; 72(4):280–4.
25. Agis H, Weltermann A, Mitterbauer G, et al. Successful treatment with arsenic trioxide of a patient with ATRA-resistant relapse of acute promyelocytic leukemia. Ann Hematol. 1999; 78(7):329–32.
26. Soignet SL. Clinical Experience of Arsenic Trioxide in Relapsed Acute Promyelocytic Leukemia. Oncologist. 2001; 6 Suppl 2:11-6.
How to Cite
Mohammadi Kanesbi M, Jarahi L, Keramati MR. Blood Parameters in Treatment with Arsenic Trioxide in Acute Promyelocytic Leukemia: A Systematic Review. Int J Hematol Oncol Stem Cell Res. 14(2):130-139.
Review Article(s)