Original Paper Acta Haematol 2000;103:67–72 Epsilon-Aminocaproic Acid Inhibits the Activity of Factor VIII Inhibitors in Patients with Severe Haemophilia A in vivo and in vitro Kanjaksha Ghosh a Shrimati Shetty a Anil Pathare b Dipika Mohanty a a Institute of Immunohaematology (ICMR), and b J.C. Patel Department of Haematology, KEM Hospital, Mumbai, India Received: April 26, 1999 Accepted: September 21, 1999 Dr. Kanjaksha Ghosh MD, MRCP, MRCPI, MRCPath, MNAMS, FACP Institute of Immunohaematology 13th floor, KEM Hospital MS Building, Parel Mumbai 400012 (India) Fax +91 22 4138521, E-Mail mohanty@bom.5.vsnl.net.in ABC Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 2000 S. Karger AG, Basel 0001–5792/00/1032–0067$17.50/0 Accessible online at: www.karger.com/journals/aha Key Words Epsilon aminocaproic acid W Factor VIII W Haemophilia A W In vitro effect W In vivo effect W Inhibitors Abstract Haemophilia patients with inhibitors pose a formidable challenge for patient management. This is particularly problematic in developing countries, where porcine fac- tor VIII, FEIBA, factor VIIa or immunoadsorption column are generally unavailable or unaffordable. Under these circumstances, any effective modality of affordable treat- ment is welcome. We investigated, both in vivo and in vitro, the effect of Â-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) sub- stantially 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 infu- sion 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 antifibrino- lytic activity. Copyright © 2000 S. Karger AG, Basel Introduction The incidence rate of development of inhibitors varies considerably in haemophilia A patients from the west [1, 2]. It may be substantially decreased in patients receiving only one brand of concentrate [3]. Several hypotheses have been put forward to explain the differences in the incidence rates of inhibitor development in haemophilia patients [4]. Irrespective of its cause, a continuously increased level of inhibitor to factor VIII heralds a change in the natural history of the disease. When a haemophilia patient with moderate-to-high level of inhibitor starts bleeding, it becomes extremely difficult to stop the bleed- ing, even under the very best circumstances provided by the developed world.