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Value of the FDP/FIB ratio in predicting early severe bleeding events in patients with newly diagnosed acute promyelocytic leukemia

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Abstract

Severe bleeding is the leading cause of early death in patients with newly diagnosed acute promyelocytic leukemia (APL). However, there are no means for hemorrhagic risk stratification in APL. This study aimed to identify optimized predictors of severe bleeding events related to APL. A total of 109 consecutive patients with newly diagnosed APL from January 2015 to April 2022 were retrospectively investigated. A systematic review of computer-based patient medical records was conducted to obtain clinical date, including baseline characteristics, routine blood examination findings, coagulation and fibrinolysis indexes, and bleeding events. Among the 109 patients, 89 were classified into the no-severe bleeding group, while 20 had severe bleeding. Compared with the patients with no severe bleeding, the patients with severe bleeding had significantly higher circulating leukemic cell percentages, disseminated intravascular coagulation (DIC) scores, D-dimer (D-D) levels, and fibrin degradation product (FDP) levels. They also had lower fibrinogen (FIB) levels and a longer prothrombin time. Multivariate analysis revealed that the circulating leukemic cell percentage (OR = 1.040, CI = 1.008–1.072, P = 0.012), FIB level (OR = 0.101, CI = 0.011–0.896, P = 0.040), and FDP level (OR = 1.012, CI = 1.000–1.024, P = 0.047) were independent risk factors for severe bleeding. FDP/FIB, D-D/FIB, and seven meaningful indicators in the single-factor analysis were included in the receiver operating characteristic (ROC) curve analysis. The results showed that FDP/FIB was the best indicator for predicting severe bleeding related to newly diagnosed APL. The area under the ROC curve of FDP/FIB was 0.915, and the best cutoff value was 61.77, with 100% sensitivity and 74.2% specificity. Statistical analysis showed a higher incidence of severe bleeding and higher DIC scores when FDP/FIB was >61.77 in APL patients. FDP/FIB has obvious advantages in predicting the degree of bleeding associated with primary promyelocytic leukemia; the greater the FDP/FIB value, the more severe the bleeding. The risk of severe bleeding was the highest when FDP/FIB > 61.77.

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References

  1. Naymagon L, Mascarenhas J (2020) Hemorrhage in acute promyelocytic leukemia: can it be predicted and prevented? Leuk Res 94:106356. https://doi.org/10.1016/j.leukres.2020.106356

    Article  CAS  PubMed  Google Scholar 

  2. Pei Y, Shi M, Song J, Niu X, Wei S, Dou L, Xiao M, Li D, Xu F, Bai Y, Sun K (2021) Absolute circulating leukemic cells as a risk factor for early bleeding events in patients with non-high-risk acute promyelocytic leukemia. Cancer Manag Res 21(13):4135–4146. https://doi.org/10.2147/CMAR.S309138

    Article  Google Scholar 

  3. Naymagon L, Moshier E, Tremblay D, Mascarenhas J (2019) Predictors of early hemorrhage in acute promyelocytic leukemia. Leuk Lymphoma 60(10):2394–2403. https://doi.org/10.1080/10428194.2019.1581187

    Article  CAS  PubMed  Google Scholar 

  4. Minamiguchi H, Fujita H, Atsuta Y, Asou N, Sakura T, Ueda Y, Sawa M, Dobashi N, Taniguchi Y, Suzuki R, Uchino Y, Tomita A, Tamaki S, Hagihara M, Fujimaki K, Yanada M, Maeda Y, Iwanaga M, Usui N et al (2020) Predictors of early death, serious hemorrhage, and differentiation syndrome in Japanese patients with acute promyelocytic leukemia. Ann Hematol 99(12):2787–2800. https://doi.org/10.1007/s00277-020-04245-6

    Article  CAS  PubMed  Google Scholar 

  5. Mantha S, Goldman DA, Devlin SM, Lee JW, Zannino D, Collins M, Douer D, Iland HJ, Litzow MR, Stein EM, Appelbaum FR, Larson RA, Stone R, Powell BL, Geyer S, Laumann K, Rowe JM, Erba H, Coutre S et al (2017) Determinants of fatal bleeding during induction therapy for acute promyelocytic leukemia in the ATRA era. Blood 129(13):1763–1767. https://doi.org/10.1182/blood-2016-10-747170

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Hambley BC, Tomuleasa C, Ghiaur G (2021) Coagulopathy in acute promyelocytic leukemia: can we go beyond supportive care? Front Med (Lausanne) 8:722614. https://doi.org/10.3389/fmed.2021.722614

    Article  PubMed  Google Scholar 

  7. Hou W, Zhang Y, Jin B, Cao W, Lu M, Yan L, Yang H, Tian X, Hou J, Fu J, Zhao H, Li H, Zhou J (2019) Factors affecting thrombohemorrhagic early death in patients with acute promyelocytic leukemia treated with arsenic trioxide alone. Blood Cells Mol Dis 79:102351. https://doi.org/10.1016/j.bcmd.2019.102351

    Article  CAS  PubMed  Google Scholar 

  8. Chu T, Wang H, Lv X, Qi J, Tang Y, Fan Y, Qiu H, Tang X, Fu C, Ruan C, Han Y, Wu DP (2021) Investigation of fibrinogen in early bleeding of patients with newly diagnosed acute promyelocytic leukemia Platelets. 32(5):677–683. https://doi.org/10.1080/09537104.2020.1799969

    Article  CAS  PubMed  Google Scholar 

  9. Breen KA, Grimwade D, Hunt BJ (2012) The pathogenesis and management of the coagulopathy of acute promyelocytic leukaemia. Br J Haematol 156(1):24–36. https://doi.org/10.1111/j.1365-2141.2011.08922.x

    Article  CAS  PubMed  Google Scholar 

  10. Sureda A, García Frade LJ, Torrado MC, García Laraña J, García Avello A (1992) A continuous spectrum of hypercoagulability exists in acute nonlymphoblastic leukemia. Acta Haematol 88(2-3):100–104. https://doi.org/10.1159/000204661

    Article  CAS  PubMed  Google Scholar 

  11. Iba T, Levy JH (2018) Inflammation and thrombosis: roles of neutrophils, platelets and endothelial cells and their interactions in thrombus formation during sepsis. J Thromb Haemost 16(2):231–241. https://doi.org/10.1111/jth.13911

    Article  CAS  PubMed  Google Scholar 

  12. Madoiwa S (2015) Recent advances in disseminated intravascular coagulation: endothelial cells and fibrinolysis in sepsis-induced DIC. J Intensive Care 3:8. https://doi.org/10.1186/s40560-015-0075-6

    Article  PubMed Central  PubMed  Google Scholar 

  13. Dally N, Hoffman R, Haddad N, Sarig G, Rowe JM, Brenner B (2005) Predictive factors of bleeding and thrombosis during induction therapy in acute promyelocytic leukemia – a single center experience in 34 patients. Thromb Res 116(2):109–114. https://doi.org/10.1016/j.thromres.2004.11.001

    Article  CAS  PubMed  Google Scholar 

  14. Chinese Society of Emergency Medicine, Editorial Board of Chinese Critical Care Medicine, Expert Group of Chinese Emergency Medicine Expert Consensus on Diagnosis and Treatment of Sepsis Complicated with Disseminated Intravascular Coagulation, Wang L, Chai Y (2017) Chinese emergency medicine expert consensus on diagnosis and treatment of sepsis complicated with disseminated intravascular coagulation. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 29(7):577–580. https://doi.org/10.3760/cma.j.issn.2095-4352.2017.07.001

    Article  Google Scholar 

  15. de la Serna J, Montesinos P, Vellenga E, Rayón C, Parody R, León A, Esteve J, Bergua JM, Milone G, Debén G, Rivas C, González M, Tormo M, Díaz-Mediavilla J, González JD, Negri S, Amutio E, Brunet S, Lowenberg B, Sanz MA (2008) Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin. Blood 111(7):3395–3402. https://doi.org/10.1182/blood-2007-07-100669

    Article  CAS  PubMed  Google Scholar 

  16. Sanz MA, Montesinos P (2010) Open issues on bleeding and thrombosis in acute promyelocytic leukemia. Thromb Res 125(Suppl 2):S51–S54. https://doi.org/10.1016/S0049-3848(10)70013-X

    Article  PubMed  Google Scholar 

  17. Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 7(1):207–214. https://doi.org/10.1002/1097-0142(19810101)47:1<207::aid-cncr2820470134>3.0.co;2-6

    Article  Google Scholar 

  18. Zhou J, Meng R, Sui X, Meng L, Jia J, Yang B (2005) Effects of administration styles of arsenic trioxide on intracellular arsenic concentration, cell differentiation and apoptosis. Haematologica 90(9):1277–1279

    CAS  PubMed  Google Scholar 

  19. Chang H, Kuo MC, Shih LY, Dunn P, Wang PN, Wu JH, Lin TL, Hung YS, Tang TC (2012) Clinical bleeding events and laboratory coagulation profiles in acute promyelocytic leukemia. Eur J Haematol 88(4):321–328. https://doi.org/10.1111/j.1600-0609.2011.01747.x

    Article  CAS  PubMed  Google Scholar 

  20. Asakura H (2014) Classifying types of disseminated intravascular coagulation: clinical and animal models. J Intensive Care 2(1):20. https://doi.org/10.1186/2052-0492-2-20

    Article  PubMed Central  PubMed  Google Scholar 

  21. Giustozzi M, Ehrlinder H, Bongiovanni D, Borovac JA, Guerreiro RA, Gąsecka A, Papakonstantinou PE, Parker WAE (2021) Coagulopathy and sepsis: pathophysiology, clinical manifestations and treatment. Blood Rev 50:100864. https://doi.org/10.1016/j.blre.2021.100864

    Article  CAS  PubMed  Google Scholar 

  22. Zhao H, Sun J, Yan L, Jin B, Hou W, Cao F, Li H, Zhou J, Zhang Y (2021) Tissue factor-bearing microparticles are a link between acute promyelocytic leukemia cells and coagulation activation: a human subject study. Ann Hematol 100(6):1473–1483. https://doi.org/10.1007/s00277-021-04533-9

    Article  CAS  PubMed  Google Scholar 

  23. Tenno T, Oberg F, Mackman N, Nilsson K, Siegbahn A (2003) PML/RARalpha plays a role for basal activity and retinoid-induced repression of the tissue factor promoter in acute promyelocytic leukemia cells. Thromb Haemost 90(5):930–939. https://doi.org/10.1160/TH03-02-0087

    Article  CAS  PubMed  Google Scholar 

  24. Zhang YM, Chen B, Wu LY, Hou JX, Fu JY (2017) Role of microparticles derived from acute promyelocytic leukemia cells in coagulopathy. Zhongguo Shi Yan Xue Ye Xue Za Zhi 25(3):693–698. https://doi.org/10.7534/j.issn.1009-2137.2017.03.011

    Article  PubMed  Google Scholar 

  25. Marcianò T, Franchini S (2021) Could a D-dimer/fibrinogen ratio have a role in ruling-out venous thromboembolism? Emerg Med J 39(12):941–944. https://doi.org/10.1136/emermed-2020-210688

    Article  PubMed  Google Scholar 

  26. Hajsadeghi S, Kerman SR, Khojandi M, Vaferi H, Ramezani R, Jourshari NM, Mousavi SA, Pouraliakbar H (2012) Accuracy of D-dimer:fibrinogen ratio to diagnose pulmonary thromboembolism in patients admitted to intensive care units. Cardiovasc J Afr 23(8):446–456. https://doi.org/10.5830/CVJA-2012-041

    Article  PubMed Central  PubMed  Google Scholar 

  27. Xu DX, Du WT, Li X, Wu ZX, Yu GF (2020) D-dimer/fibrinogen ratio for the prediction of progressive hemorrhagic injury after traumatic brain injury. Clin Chim Acta 507:143–148. https://doi.org/10.1016/j.cca.2020.04.022

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank all members of the study team, the patients, and their families.

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All authors contributed to the study’s conception and design. Shanshan Li and Yanhua Su conceived and designed the study. Shanshan Li, Yu Zheng, and Fei Li performed data acquisition, analyses, and interpretation. Shanshan Li drafted the manuscript. Yujuan Gao and Yu Zheng critically revised the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Yujuan Gao.

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Li, S., Gao, Y., Li, F. et al. Value of the FDP/FIB ratio in predicting early severe bleeding events in patients with newly diagnosed acute promyelocytic leukemia. Ann Hematol 102, 787–794 (2023). https://doi.org/10.1007/s00277-023-05122-8

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