Nafamostat Mesilate as a Regional Anticoagulant in Patients with Bleeding Complications during Extracorporeal Membrane Oxygenation

Park, Jin Han; Her, Charles; Min, Ho-Ki; Kim, Dong-Kie; Park, Si-Hyung; Jang, Hang-Jea

doi:10.5301/ijao.5000451

Cited by 27 publications

(27 citation statements)

References 13 publications

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“…It has short duration of action in blood due to a 5-8 minutes elimination half-life and has the theoretical advantage of extracorporeal elimination coupled with reduced systemic anticoagulation [61]. This drug, dominantly available in Japan and Korea, had been safely used in the critically ill with high bleeding risk in some observational studies [62][63][64]. The reported filter lifespan of nafamostat-anticoagulated CRRT ranged from 22 to 25.5 hours and the bleeding incidence ranged from 4% to 6.6% [65,66].…”

Section: Anticoagulation-free Versus Nafamostatmentioning

confidence: 99%

Continuous renal replacement therapy without anticoagulation in critically ill patients at high risk of bleeding: a systematic review and meta-analysis

Zhang

Bai

et al. 2019

Preprint

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Background: Continuous renal replacement therapy (CRRT) has been widely used in the critical care setting and anticoagulation is usually necessitated. However, critically ill patients are commonly at incremental risk of bleeding, which contributed to the hesitation of anticoagulant use for CRRT in clinical practice. The current guideline recommended CRRT proceed without anticoagulation in patients with contraindication to citrate and increased bleeding risk. Nevertheless, the efficacy of anticoagulation-free CRRT remains inconsistent. Therefore, the purpose of our present systematic review is to evaluate the efficacy and safety of anticoagulant-free CRRT based on the current literatures. Methods: We conducted a comprehensive search of PubMed (US National Library of Medicine, Bethesda, MD, USA), Cochrane Library databases and EMBASE from database inception to January 12, 2019 for potential candidate studies. Studies included adult critically ill (age > 18 years) patients with increased bleeding risk, and underwent CRRT without anticoagulation were considered for the inclusion. Results: Finally, 17 observational studies and 3 randomized controlled trials with 1615 patients were included in our present meta-analysis. There was no significant difference in filter lifespan between the anticoagulation-free and systemic heparin group. The filter lifespan was significantly prolonged in the citrate (WMD -23.01, 95%CI [-28.62, -17.39], P < 0.001; I 2 = 0%, P = 0.53) and nafamostat (WMD -8.4, 95%CI [-9.9, -6.9], P < 0.001; I 2 = 33.7%, P = 0.21) groups, compared with anticoagulation-free group. The averaged filter lifespan of the anticoagulation-free CRRT ranged from 10.2 to 52.5 hours. Conclusion: The filter lifespan in anticoagulation-free patients with increased bleeding risk was comparable to that in patients without increased bleeding risk underwent systemic heparin anticoagulation CRRT. Nafamostat was not recommended for CRRT anticoagulation due to its drawbacks. Currently, the optimal choice of anticoagulation strategy for critically ill patients without citrate contraindications at high risk of bleeding should be regional citrate anticoagulation. Further studies should focus on the special cut-off value of activated partial thromboplastin time (APTT), international normalized ratio (INR) and platelet (PLT) count, at which the anticoagulation-free CRRT would be beneficial. Key words: Anticoagulation, critically ill patients, continuous renal replacement therapy, filter failure, bleeding

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Section: Anticoagulation-free Versus Nafamostatmentioning

confidence: 99%

Continuous renal replacement therapy without anticoagulation in critically ill patients at high risk of bleeding: a systematic review and meta-analysis

Zhang

Bai

et al. 2019

Preprint

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“…Lim et al90 found that NM was associated with a higher risk of bleeding than heparin in ECMO patients. In contrast, Park et al91 and Han et al92 reported that NM was a safe alternative anticoagulant for ECMO patients with a high risk of bleeding. Nagaya et al93 reported the use of NM in 12 neonates on ECMO who had a high risk of bleeding that was well controlled in eight of these 12 neonates.…”

mentioning

confidence: 93%

Heparin‐induced thrombocytopenia complicating extracorporeal membrane oxygenation support: Review of the literature and alternative anticoagulants

Pollak

2019

Journal of Thrombosis and Haemostasis

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Heparin‐induced thrombocytopenia (HIT) is a life‐threatening prothrombotic, immune‐mediated complication of unfractionated heparin and low molecular weight heparin therapy. HIT is characterized by moderate thrombocytopenia 5‐10 days after initial heparin exposure, detection of platelet‐activating anti‐platelet factor 4/heparin antibodies and an increased risk of venous and arterial thrombosis. Extracorporeal membrane oxygenation (ECMO) is a form of mechanical circulatory support used in critically ill patients with respiratory or cardiac failure. Systemic anticoagulation is used to alleviate the thrombotic complications that may occur when blood is exposed to artificial surfaces within the ECMO circuit. Therefore, when HIT complicates patients on ECMO support, it is associated with a high thrombotic morbidity and mortality. The risk for HIT correlates with the accumulative dosage of heparin exposure. In ECMO patients receiving continuous infusion of heparin for circuit patency, the risk for HIT is not neglected and must be thought of in the differential diagnosis of the appropriate clinical and laboratory circumstances. The following article reviews the current knowledge in HIT complicating ECMO patients and the alternative anticoagulation options in the presence of HIT.

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“…[6][7][8][9][10][11] Furthermore, strategies described to prevent further hemorrhage in patients with active bleeding while on ECMO include the use of fresh-frozen plasma, vitamin K, aprotinin, and recombinant activated factor VII, as well as avoiding the concomitant use of heparin and using only nafamostat mesilate as a regional anticoagulant. [12][13][14] Aminocaproic acid is a lysine analogue effective in certain bleeding disorders due to its inhibitor effect on plasmin. Despite the theoretical risk of in-circuit thrombosis, retrospective studies indicate that its use is safe in patients on ECMO who develop life-threatening hemorrhage.…”

Section: Discussionmentioning

confidence: 99%

Use of Aminocaproic Acid in Combination With Extracorporeal Membrane Oxygenation in a Case of Leptospirosis Pulmonary Hemorrhage Syndrome

Mendirichaga

Budhrani

et al. 2017

Clin Med Insights Circ Respir Pulm Med

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A 32-year-old man presented with a 10-day history of fever, chills, nausea, vomiting, myalgia, nonproductive cough, and worsening dyspnea after freshwater swimming in the Caribbean 1 week prior to presentation. Shortly after arrival at the hospital, the patient developed severe respiratory distress with massive hemoptysis. Based on serologic workup, he was diagnosed with leptospirosis pulmonary hemorrhage syndrome leading to diffuse alveolar hemorrhage, severe hypoxemic respiratory failure, and multiorgan failure. He received appropriate antibiotic coverage along with hemodynamic support with norepinephrine and vasopressin, mechanical ventilation, and renal replacement therapy in an intensive care unit. Introduction of extracorporeal membrane oxygenation was initiated to provide lung-protective ventilation supporting the recovery of his pulmonary function. Aminocaproic acid was used to stop and prevent further alveolar hemorrhage. He fully recovered thereafter; however, it is uncertain whether it was the use of aminocaproic acid that led to the resolution of his disease.

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Nafamostat Mesilate as a Regional Anticoagulant in Patients with Bleeding Complications during Extracorporeal Membrane Oxygenation

Abstract: Nafamostat mesilate, with which we can reduce anticoagulation values of patient to a safe level without losing the ECMO anticoagulation values is expected to be useful as a regional anticoagulant in patients with bleeding complications or a high risk of bleeding during ECMO.

Cited by 27 publications

References 13 publications

Continuous renal replacement therapy without anticoagulation in critically ill patients at high risk of bleeding: a systematic review and meta-analysis

Continuous renal replacement therapy without anticoagulation in critically ill patients at high risk of bleeding: a systematic review and meta-analysis

Heparin‐induced thrombocytopenia complicating extracorporeal membrane oxygenation support: Review of the literature and alternative anticoagulants

Use of Aminocaproic Acid in Combination With Extracorporeal Membrane Oxygenation in a Case of Leptospirosis Pulmonary Hemorrhage Syndrome

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