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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
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Current opinion on inhibitor treatment options

Prasad Mathew1

  • 1Department of Pediatrics, University of New Mexico, Albuquerque, NM 87113, USA. PMathew@salud.unm.edu

Seminars in Hematology
|May 13, 2006
PubMed

Inhibitor development in patients with hemophilia complicates hemostatic management. Currently, high doses of factor concentrates are used to override low-titer, low-responding inhibitors during acute bleeding episodes. Bypassing agents, such as the activated prothrombin complex concentrate (aPCC), Factor Eight Inhibitor Bypassing Activity, Anti-Inhibitor Coagulant Complex, Vapor Heated (FEIBA; Baxter AG, Vienna, Austria), and activated recombinant factor VII (rFVIIa; NovoSeven, Novo Nordisk A/S, Bagsvaerd, Denmark), are commonly used to treat acute bleeding episodes in patients with high-titer, high-responding inhibitors, whereas long-term therapeutic options include inhibitor eradication using immune tolerance induction. Neither FEIBA nor rFVIIa can be monitored with a laboratory assay, making it difficult to establish optimal dosages. Comparative studies evaluating the efficacy of FEIBA and rFVIIa for bleed control have been sparse, prompting investigators to initiate crossover comparison studies to assess the efficacy and cost of aPCC and rFVIIa in the treatment of joint hemorrhages. Both the cost of therapy and the outcome of therapy will need to be considered in the development of future hemostatic agents for patients with inhibitors.

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