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Comparison of gabexate mesilate and nafamostat mesilate for disseminated intravascular coagulation associated with hematological malignancies

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Abstract

We evaluated clinical outcomes of disseminated intravascular coagulation (DIC) in patients with hematological malignancies treated with synthetic protease inhibitors (SPIs) and compared the effects of gabexate mesilate (FOY) and nafamostat mesilate (FUT). We retrospectively examined 127 patients [acute myeloid leukemia (n = 48), acute lymphoblastic leukemia (n = 25), and non-Hodgkin lymphoma (n = 54)] with DIC, who were diagnosed according to Japanese Ministry of Health, Labour and Welfare criteria and treated with SPIs [FOY (n = 55) and FUT (n = 72)] at our hospital from 2006 to 2015. The DIC resolution rates on days 7 and 14 were 42.6% and 62.4%, respectively. No significant differences were observed in DIC resolution rates between the FUT and FOY groups [40.3% vs. 45.5% (day 7), P = 0.586; 56.3% vs. 69.8% (day 14), P = 0.179, respectively]. Multivariate analysis revealed that response to chemotherapy was the only independent predictor of DIC resolution on days 7 and 14 (ORR 2.81, 95% CI 1.32–5.98, P = 0.007; ORR 2.51, 95% CI 1.12–5.65, P = 0.026). Resolution of DIC was correlated with improvement of background hematological malignancies, and no significant differences were observed between the two SPIs.

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References

  1. Asakura H, Takahashi H, Uchiyama T, Eguchi Y, Okamoto K, Kawasugi K, et al. DIC subcommittee of the Japanese Society on Thrombosis and Hemostasis. Proposal for new diagnostic criteria for DIC from the Japanese Society on Thrombosis and Hemostasis. Thromb J. 2016;14:42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Wada H, Asakura H, Okamoto K, Iba T, Uchiyama T, Kawasugi K, et al. Japanese Society of Thrombosis Hemostasis/DIC subcommittee. Expert consensus for the treatment of disseminated intravascular coagulation in Japan. Thromb Res. 2010;125:6–11.

    Article  CAS  PubMed  Google Scholar 

  3. Levi M, Ten Cate H. Disseminated intravascular coagulation. N Engl J Med. 1999;341:586–92.

    Article  CAS  PubMed  Google Scholar 

  4. Gando S. Microvascular thrombosis and multiple organ dysfunction syndrome. Crit Care Med. 2010;38(2 Suppl):35–42.

    Article  Google Scholar 

  5. Iba T, Thachil J. Present and future of anticoagulant therapy using antithrombin and thrombomodulin for sepsis-associated disseminated intravascular coagulation: a perspective from Japan. Int J Hematol. 2016;103:253–61.

    Article  CAS  PubMed  Google Scholar 

  6. Ohno H, Kosaki G, Kambayashi J, Imaoka S, Hirata F. FOY: [ethyl P-(6-guanidinohexanoyloxy) benzoate] methanesulfonate as a serine proteinase inhibitor. I. Inhibition of thrombin and factor Xa in vitro. Thromb Res. 1980;19:579–88.

    Article  CAS  PubMed  Google Scholar 

  7. Hitomi Y, Ikari N, Fujii S. Inhibitory effect of a new synthetic protease inhibitor (FUT-175) on the coagulation system. Haemostasis. 1985;15:164–8.

    CAS  PubMed  Google Scholar 

  8. Kobayashi N, Maekawa T, Takada M, Tanaka H, Gonmori H. Criteria for diagnosis of DIC based on the analysis of clinical and laboratory findings in 345 DIC patients collected by the Research Committee on DIC in Japan. Bibl Haematol. 1983;49:265–75.

    Google Scholar 

  9. Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M, Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001;86:1327–30.

    Article  CAS  Google Scholar 

  10. Asakura H. Classifying types of disseminated intravascular coagulation: clinical and animal models. J Intensive Care. 2014;2:20.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Saito H, Maruyama I, Shimazaki S, Yamamoto Y, Aikawa N, Ohno R, et al. Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial. J Thromb Haemost. 2007;5:31–41.

    Article  CAS  PubMed  Google Scholar 

  12. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48:452–8.

    Article  CAS  PubMed  Google Scholar 

  13. Ino Y, Suzuki K, Sato T, Iwaki M. Comparative studies of nafamostat mesilate and various serine protease inhibitors in vitro. Folia Pharmacol Jpn. 1986;88:449–55.

    Article  CAS  Google Scholar 

  14. Iwaki M, Ino Y, Motoyoshi A, Ozeki M, Sato T, Kurumi M, et al. Pharmacological studies of FUT-175, nafamostat mesilate. V. Effects on the pancreatic enzymes and experimental acute pancreatitis in rats. Jpn J Pharmacol. 1986;41:155–62.

    Article  CAS  PubMed  Google Scholar 

  15. Shibata S, Takahashi H, Aoki N, Takahashi H, Aoki N, Matsuda T, et al. Evaluation of clinical effect of FUT-175 on DIC: multi-center clinical comparative study. Rinsho Kenkyu. 1988;65:921–40.

    Google Scholar 

  16. Kosaki G, Kambayashi J, Hirabayashi A, Mori K, Uchida T, Abe T, et al. Evaluation of clinical effect of FOY on DIC: multi-center clinical comparative study. Igaku no Ayumi. 1983;124:144–54.

    Google Scholar 

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Authors and Affiliations

Authors

Contributions

DM collected data and wrote the manuscript; SF collected data and wrote the manuscript; YK and TO designed this report, interpreted the results and wrote the manuscript; YS, TI, SK, YT, SI, SO, TN, KM, KU, HN, RY, KM, YK, MS, CY, MA, KH, KS, IO, KO, KM, reviewed the manuscript, contributed to the interpretation of the data, and approved the final version.

Corresponding author

Correspondence to Yoshinobu Kanda.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. We declare that we have no conflicts of interest.

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Minakata, D., Fujiwara, Si., Ikeda, T. et al. Comparison of gabexate mesilate and nafamostat mesilate for disseminated intravascular coagulation associated with hematological malignancies. Int J Hematol 109, 141–146 (2019). https://doi.org/10.1007/s12185-018-02567-w

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