Nafamostat mesilate (NFM) is used as an
anticoagulant during
hemodialysis in patients who have had complications due to
hemorrhages. The formation of precipitates, which could lead to the interruption of
hemodialysis has been reported when NFM is infused into blood during
hemodialysis. We report herein on an examination of possible factors that could cause this. The effects of
electrolytes such as
phosphates,
citrates or
succinates on the formation of precipitates were examined by mixing NFM with aqueous solutions or plasma that contained these
electrolytes. The formation of precipitates was observed in all
electrolyte solutions when higher concentrations of NFM were mixed at around physiological pH. In the case of plasma, precipitates were observed when solutions containing higher concentrations of NFM were mixed with plasma that contained
phosphate and
citrate. In addition, the formation of precipitates under dynamic conditions where NFM was infused into flowing
electrolyte solutions was also evaluated. The data suggested that such precipitates might be formed and disrupt the blood flow and/or an NFM infusion when NFM is infused into blood flowing in the
hemodialysis circuit. The findings presented herein suggest the serum levels of anionic
electrolytes (e.g.,
phosphate), the type of
excipients present in pharmaceutical products (e.g.,
succinic acid or
citric acid), the concentration of NFM used for the infusion or the rates of NFM infusion and blood flow are all factors that could affect precipitate formation during NFM infusions for
hemodialysis.