title: Epsilon-aminocaproic acid inhibits the activity of factor VIII inhibitors in patients with severe haemophilia A in vivo and in vitro.
abstract: Haemophilia patients with inhibitors pose a formidable challenge for patient management. This is particularly problematic in developing countries, where porcine factor VIII, FEIBA, factor VIIa or immunoadsorption column are generally unavailable or unaffordable. Under these circumstances, any effective modality of affordable treatment is welcome. We investigated, both in vivo and in vitro, the effect of epsilon-aminocaproic acid (EACA) on the inhibitory activity of factor VIII inhibitor. It was found that in vitro EACA (final concentration 1.25-5 mg/ml) substantially inhibited the activity of the inhibitors, while the same concentration of EACA had no effect on other immunological reactions like red cell agglutination and immunofluorescence. The inhibitory action of EACA on factor VIII inhibitor was also confirmed in an improvised antigen-binding ELISA system. Further, the inhibitory activity of EACA was confirmed in 2 patients, in whom the inhibitory activity persisted for 15 min following infusion of EACA (100 mg/kg over 10 min). EACA was found to be even more effective in local wound application in patients of haemophilia A with inhibitors. EACA at the concentration cited did not act as an inhibitor of factor VIII inhibitor through occupancy of lysine binding sites. The inhibitory activity of EACA on factor VIII inhibitor was equally seen with recombinant factor VIII also; hence this action cannot be explained by its antifibrinolytic activity.
authors.affiliation: Institute of Immunohaematology (ICMR), KEM Hospital, Mumbai, India. mohanty@bom.5.vsnl.net.in
authors.forename: K
authors.initials: K
authors.lastname: Ghosh
authors.forename: S
authors.initials: S
authors.lastname: Shetty
authors.forename: A
authors.initials: A
authors.lastname: Pathare
authors.forename: D
authors.initials: D
authors.lastname: Mohanty
mesh_terms: D000293:Adolescent; D000328:Adult; D015119:Aminocaproic Acid / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D000933:Antifibrinolytic Agents / Q000494:pharmacology; D002648:Child; D004305:Dose-Response Relationship, Drug; D005169:Factor VIII / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000627:therapeutic use; D006467:Hemophilia A / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D006801:Humans; D007262:Infusions, Intravenous; D007518:Isoantibodies / Q000276:immunology*; D008297:Male
chemical_list: D000933:Antifibrinolytic Agents; D007518:Isoantibodies; D005169:Factor VIII; D015119:Aminocaproic Acid