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Nafamostat mesilate, a noncalcium compound, as an anticoagulant, induces calcium‐dependent haemolysis when infused with packed erythrocytes
Author(s) -
Fujita H.,
Sakuma R.,
Fujimoto S.,
Hazama Y.,
Ohtake C.,
Moriyama A.,
Kuhara K.,
Nishimura S.
Publication year - 2012
Publication title -
transfusion medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.471
H-Index - 59
eISSN - 1365-3148
pISSN - 0958-7578
DOI - 10.1111/j.1365-3148.2012.01154.x
Subject(s) - haemolysis , pharmacology , lactate dehydrogenase , calcium , hemolysis , incubation , chemistry , anticoagulant , medicine , extracellular , phosphatidylserine , biochemistry , immunology , enzyme , membrane , phospholipid
Background: Nafamostat mesilate (NM), a protease inhibitor, is available for acute pancreatitis and disseminated intravascular coagulopathy and is used as an anticoagulant for haemodialysis in Japan. Co‐infusion of red cell concentrates (RCC) and intravenous drugs is usually contraindicated. Because of limited venous access, adherence to the guidelines may be compromised in some clinical settings. Therefore, we investigated the influence of co‐infusion of RCC and various anticoagulants on haemolysis in vitro . Methods: We investigated the effect of co‐incubation of RCC and various anticoagulant drugs [NM, gabexate mesilate (GM), heparin] in packed erythrocytes. We evaluated haemolysis using lactate dehydrogenase and free haemoglobin. In addition, we also evaluated the influence of co‐incubation on phosphatidylserine (PS) expression on the erythrocyte membrane. Results: GM and NM induced haemolysis in a dose‐dependent manner, which was inhibited by removal of citrate and pretreatment with the calcium chelator, ethylenediaminetetraacetic acid. In a dynamic experiment using an infusion pump, NM not only induced haemolysis during co‐infusion with RCC but also elevated PS expression dependent on extracellular calcium. Conclusion: NM and GM induce haemolysis in packed erythrocytes in the presence of citrate that is dependent on extracellular calcium.