title: Nafamostat mesilate, a noncalcium compound, as an anticoagulant, induces calcium-dependent haemolysis when infused with packed erythrocytes.
abstract: 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.
  
  
  CONCLUSIONS
  NM and GM induce haemolysis in packed erythrocytes in the presence of citrate that is dependent on extracellular calcium.
authors.affiliation: Department of Transfusion Medicine, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan. yuketsuka@bokutoh-hp.metro.tokyo.jp
authors.forename: H
authors.initials: H
authors.lastname: Fujita
authors.forename: R
authors.initials: R
authors.lastname: Sakuma
authors.forename: S
authors.initials: S
authors.lastname: Fujimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Hazama
authors.forename: C
authors.initials: C
authors.lastname: Ohtake
authors.forename: A
authors.initials: A
authors.lastname: Moriyama
authors.forename: K
authors.initials: K
authors.lastname: Kuhara
authors.forename: S
authors.initials: S
authors.lastname: Nishimura
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology*; D001550:Benzamidines; D002118:Calcium / Q000502:physiology*; D002951:Citrates; D019343:Citric Acid / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004492:Edetic Acid / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects*; D005434:Flow Cytometry; D016670:Gabexate / Q000494:pharmacology; D005947:Glucose; D006146:Guanidines / Q000494:pharmacology*; D006454:Hemoglobins / Q000032:analysis; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008563:Membrane Lipids / Q000097:blood; D010718:Phosphatidylserines / Q000097:blood; D012996:Solutions
chemical_list: D000925:Anticoagulants; D001550:Benzamidines; D002951:Citrates; D006146:Guanidines; D006454:Hemoglobins; D008563:Membrane Lipids; D010718:Phosphatidylserines; D012996:Solutions; D019343:Citric Acid; D016670:Gabexate; C007077:citrate phosphate dextrose; D004492:Edetic Acid; D007770:L-Lactate Dehydrogenase; D005947:Glucose; D002118:Calcium; C032855:nafamostat