Nafamostat mesilate in anticoagulation of continuous renal replacement therapy_West China Medical Journal

Authors：

 Nobuya Kitamura

Department of Emergency and Critical Care Medicine, Kimitsu Chuo Hospital, Kisarazu, Chiba 292-8535, Japan;

Corresponding author：

Nobuya Kitamura, Email: kitaccm-cib@umin.ac.jp

Keywords：

Nafamostat mesilate; Anticoagulant; Bleeding complication; Activated clotting time; Filter life time; Citrate

DOI：

10.7507/1002-0179.201806036

Video：

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In the intensive care units of Japan, nafamostat mesilate (NM) is the most used anticoagulant of continuous blood purification, with the rate of up to 85%. Its biggest characteristic is not to reduce the life of the filter in the group of patients with high risk of bleeding, and it can be safely used. However, there are not a few reports about severe anaphylaxis, when the symptoms of anaphylaxis is recognized after the start of continuous renal replacement therapy, it should be kept in mind that it is NM hypersensitivity. In addition, for an expensive drug, it may be required to be limited in the cases of risk of bleeding complications. NM has been developed for nearly 30 years, so it has high reliability in Japan. However, in the same case, regional citrate anticoagulation is recommended internationally. It may need a randomized controlled trial with regional citrate anticoagulation to prove the real effectiveness of NM.

Citation： Nobuya Kitamura. Nafamostat mesilate in anticoagulation of continuous renal replacement therapy. West China Medical Journal, 2018, 33(7): 801-805. doi: 10.7507/1002-0179.201806036 Copy

1.	Arimura T, Abe M, Shiga H, et al. Clinical study of blood purification therapy in critical care in Japan: results from the survey research of the Japan Society for Blood Purification in Critical Care in 2013. J Artif Organs, 2017, 20(3): 244-251.
2.	Hirasawa H, Sugai T, Ohake S, et al. Continuous hemofiltration in the treatment of anuric multiple organ failure. Artif Organs, 1990, 14(Suppl 2): 117-119.
3.	Hirasawa H, Sugai T, Ohtake Y, et al. Continuous hemofiltration and hemodiafiltration in the management of multiple organ failure. Contrib Nephrol, 1991, 93(93): 42-46.
4.	Kitamura N, Kako K, Igarashi K, et al. Dialysis disequilibrium syndrome on neurointensive care: the role of continuous hemodiafiltration. Kyukyuigaku, 2013(37): 1637-1641.
5.	Hattori N, Oda S. Cytokine-adsorbing hemofilter: old but new modality for septic acute kidney injury. Renal Replace Ther. 2016, 41: 2.
6.	Ohtake Y, Hirasawa H, Sugai T, et al. Nafamostat mesylate as anticoagulant in continuous hemofiltration and continuous hemodiafiltration. Contrib Nephrol, 1991, 93(93): 215-217.
7.	van de Wetering J, Westendorp RG, van der Hoeven JG, et al. Heparin use in continuous renal replacement procedures: the struggle between filter coagulation and patient hemorrhage. J Am Soc Nephrol, 1996, 7(1): 145-150.
8.	Fujii S, Hitomi Y. New synthetic inhibitors of C1r, C1 esterase, thrombin, plasmin, kallikrein and trypsin. Biochim Biophys Acta, 1981, 661(2): 342-345.
9.	Kitawaki T, Uchino S, Kamioka E, et al. Nafamostat mesialte vs. low dose heparin for anticoagulation during continuous renal replacement therapy. J Jpn Soc Intensive Care Med, 2007, 14: 563-569.
10.	Choi JY, Kang YJ, Jang HM, et al. Nafamostat mesilate as an anticoagulant during continuous renal replacement therapy in patients with high bleeding risk: a randomized clinical trial. Medicine (Baltimore), 2015, 94(52): e2392.
11.	Hwang SD, Hyun YK, Moon SJ, et al. Nafamostat mesilate for anticoagulation in continuous renal replacement therapy. Int J Artif Organs, 2013, 36(3): 208-216.
12.	Makino S, Egi M, Kita H, et al. Comparison of nafamostat mesilate and unfractionated heparin as anticoagulants during continuous renal replacement therapy. Int J Artif Organs, 2016, 39(1): 16-21.
13.	Maruyama H, Miyakawa Y, Gejyo F, et al. Anaphylactoid reaction induced by nafamostat mesilate in a hemodialysis patient. Nephron, 1996, 74(2): 468-469.
14.	Yamazato M, Mano R, Oshiro-Chinen S, et al. Severe abdominal pain associated with allergic reaction to nafamostat mesilate in a chronic hemodialysis patient. Intern Med, 2002, 41(10): 864-866.
15.	厚生労働省. 重篤副作用疾患別対応マニュアル: アナフィラキシー.(2010-06-25) [2018-06-01]. http://www.mhlw.go.jp/topics/2006/11/dl/tp1122-1h01.pdf.
16.	Kamo A, Abe T, Magono S, et al. A case of nafamostat mesilate hypersensitivity with an acute and atypical change in blood volume variations during hemodialysis. J Jpn Soc Blood Purif Crit Care, 2013(4): 168-171.
17.	Kim HS, Lee KE, Oh JH, et al. Cardiac arrest caused by nafamostat mesilate. Kidney Res Clin Pract, 2016, 35(3): 187-189.
18.	Hirayama T, Nosaka N, Okawa Y, et al. AN69T membranes adsorb nafamostat mesylate and affect the management of anticoagulant therapy: a retrospective. J Intensive Care, 2017, 5: 46.
19.	Kunimoto Y, Hara Y, Kawaji T, et al. The influence of nafamostat mesilate administration on the lifetime of AN69ST-continuous hemofiltration. J Jpn Soc Blood Purif Crit Care, 2017(8): 48-53.
20.	Iwama H, Watanabe K, Obara S. In vitro relationship between the blood nafamostat concentration and activated coagulation time. Can J Anaesth, 2003, 50(6): 621-622.
21.	Akizawa T, Kosikawa S, Iwamoto S, et al. Pharmacokinetic studies of regional anticoagulant-FUT-175 in hemodialysis. Kidney Dial, 1989, 26: 145-151.
22.	Inoue Y, Tsychihashi Y, Ohsaka M, et al. Optimal target of ACT for an appropriate nafamostat mesilate dosage during continuous renal replacement therapy. J Jpn Soc Blood Purif Crit Care, 2010(1): 124-130.
23.	Miyatake Y, Makino S, Kubota K, et al. Association between intra-circuit activated clotting time and incidence of bleeding complications during continuous renal replacement therapy using nafamostat mesilate: a retrospective pilot observational study. Kobe J Med Sci, 2017, 63: E30-E36.
24.	Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl, 2012, 2(1): 1-138.
25.	Liu C, Mao Z, Kang H, et al. Regional citrate versus heparin anticoagulation for continuous renal replacement therapy in critical ill patients: a meta-analysis with trial sequential analysis of randomized controlled trials. Crti Care, 2016, 20: 144.
26.	Stucker F, Ponte B, Tataw J, et al. Efficacy and safety of citrate-based anticoagulation compared to heparin in patients with acute kidney injury requiring continuous real replacement therapy: a randomized controlled trial. Crit Care, 2015, 19: 91.
27.	Okuda A, Uchino S, Shibasaki T, et al. Experience of the continuous hemodialysis with citrate anticoagulation. J Jpn Soc Intensive Care Med, 2013(20): 653-654.

1. Arimura T, Abe M, Shiga H, et al. Clinical study of blood purification therapy in critical care in Japan: results from the survey research of the Japan Society for Blood Purification in Critical Care in 2013. J Artif Organs, 2017, 20(3): 244-251.
2. Hirasawa H, Sugai T, Ohake S, et al. Continuous hemofiltration in the treatment of anuric multiple organ failure. Artif Organs, 1990, 14(Suppl 2): 117-119.
3. Hirasawa H, Sugai T, Ohtake Y, et al. Continuous hemofiltration and hemodiafiltration in the management of multiple organ failure. Contrib Nephrol, 1991, 93(93): 42-46.
4. Kitamura N, Kako K, Igarashi K, et al. Dialysis disequilibrium syndrome on neurointensive care: the role of continuous hemodiafiltration. Kyukyuigaku, 2013(37): 1637-1641.
5. Hattori N, Oda S. Cytokine-adsorbing hemofilter: old but new modality for septic acute kidney injury. Renal Replace Ther. 2016, 41: 2.
6. Ohtake Y, Hirasawa H, Sugai T, et al. Nafamostat mesylate as anticoagulant in continuous hemofiltration and continuous hemodiafiltration. Contrib Nephrol, 1991, 93(93): 215-217.
7. van de Wetering J, Westendorp RG, van der Hoeven JG, et al. Heparin use in continuous renal replacement procedures: the struggle between filter coagulation and patient hemorrhage. J Am Soc Nephrol, 1996, 7(1): 145-150.
8. Fujii S, Hitomi Y. New synthetic inhibitors of C1r, C1 esterase, thrombin, plasmin, kallikrein and trypsin. Biochim Biophys Acta, 1981, 661(2): 342-345.
9. Kitawaki T, Uchino S, Kamioka E, et al. Nafamostat mesialte vs. low dose heparin for anticoagulation during continuous renal replacement therapy. J Jpn Soc Intensive Care Med, 2007, 14: 563-569.
10. Choi JY, Kang YJ, Jang HM, et al. Nafamostat mesilate as an anticoagulant during continuous renal replacement therapy in patients with high bleeding risk: a randomized clinical trial. Medicine (Baltimore), 2015, 94(52): e2392.
11. Hwang SD, Hyun YK, Moon SJ, et al. Nafamostat mesilate for anticoagulation in continuous renal replacement therapy. Int J Artif Organs, 2013, 36(3): 208-216.
12. Makino S, Egi M, Kita H, et al. Comparison of nafamostat mesilate and unfractionated heparin as anticoagulants during continuous renal replacement therapy. Int J Artif Organs, 2016, 39(1): 16-21.
13. Maruyama H, Miyakawa Y, Gejyo F, et al. Anaphylactoid reaction induced by nafamostat mesilate in a hemodialysis patient. Nephron, 1996, 74(2): 468-469.
14. Yamazato M, Mano R, Oshiro-Chinen S, et al. Severe abdominal pain associated with allergic reaction to nafamostat mesilate in a chronic hemodialysis patient. Intern Med, 2002, 41(10): 864-866.
15. 厚生労働省. 重篤副作用疾患別対応マニュアル: アナフィラキシー.(2010-06-25) [2018-06-01]. http://www.mhlw.go.jp/topics/2006/11/dl/tp1122-1h01.pdf.
16. Kamo A, Abe T, Magono S, et al. A case of nafamostat mesilate hypersensitivity with an acute and atypical change in blood volume variations during hemodialysis. J Jpn Soc Blood Purif Crit Care, 2013(4): 168-171.
17. Kim HS, Lee KE, Oh JH, et al. Cardiac arrest caused by nafamostat mesilate. Kidney Res Clin Pract, 2016, 35(3): 187-189.
18. Hirayama T, Nosaka N, Okawa Y, et al. AN69T membranes adsorb nafamostat mesylate and affect the management of anticoagulant therapy: a retrospective. J Intensive Care, 2017, 5: 46.
19. Kunimoto Y, Hara Y, Kawaji T, et al. The influence of nafamostat mesilate administration on the lifetime of AN69ST-continuous hemofiltration. J Jpn Soc Blood Purif Crit Care, 2017(8): 48-53.
20. Iwama H, Watanabe K, Obara S. In vitro relationship between the blood nafamostat concentration and activated coagulation time. Can J Anaesth, 2003, 50(6): 621-622.
21. Akizawa T, Kosikawa S, Iwamoto S, et al. Pharmacokinetic studies of regional anticoagulant-FUT-175 in hemodialysis. Kidney Dial, 1989, 26: 145-151.
22. Inoue Y, Tsychihashi Y, Ohsaka M, et al. Optimal target of ACT for an appropriate nafamostat mesilate dosage during continuous renal replacement therapy. J Jpn Soc Blood Purif Crit Care, 2010(1): 124-130.
23. Miyatake Y, Makino S, Kubota K, et al. Association between intra-circuit activated clotting time and incidence of bleeding complications during continuous renal replacement therapy using nafamostat mesilate: a retrospective pilot observational study. Kobe J Med Sci, 2017, 63: E30-E36.
24. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl, 2012, 2(1): 1-138.
25. Liu C, Mao Z, Kang H, et al. Regional citrate versus heparin anticoagulation for continuous renal replacement therapy in critical ill patients: a meta-analysis with trial sequential analysis of randomized controlled trials. Crti Care, 2016, 20: 144.
26. Stucker F, Ponte B, Tataw J, et al. Efficacy and safety of citrate-based anticoagulation compared to heparin in patients with acute kidney injury requiring continuous real replacement therapy: a randomized controlled trial. Crit Care, 2015, 19: 91.
27. Okuda A, Uchino S, Shibasaki T, et al. Experience of the continuous hemodialysis with citrate anticoagulation. J Jpn Soc Intensive Care Med, 2013(20): 653-654.

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