32. Combination/Sequential Use of Bypassing Agents

  1. Emérito-Carlos Rodríguez-Merchán MD, PHD2,3 and
  2. Leonard A. Valentino MD4
  1. Alessandro Gringeri MD, MSc

Published Online: 12 MAY 2011

DOI: 10.1002/9781119979401.ch32

Current and Future Issues in Hemophilia Care

Current and Future Issues in Hemophilia Care

How to Cite

Gringeri, A. (2011) Combination/Sequential Use of Bypassing Agents, in Current and Future Issues in Hemophilia Care (eds E.-C. Rodríguez-Merchán and L. A. Valentino), Wiley-Blackwell, Oxford, UK. doi: 10.1002/9781119979401.ch32

Editor Information

  1. 2

    Department of Orthopedic Surgery and Hemophilia Unit, La Paz University Hospital, Spain

  2. 3

    School of Medicine, Autonomous University, Madrid, Spain

  3. 4

    Hemophilia and Thrombophilia Center, Rush University Medical Center, Chicago, IL, USA

Author Information

  1. Department of Medicine and Medical Specialities, Fondazione IRCCS Cà, Granda – Ospedale, Maggiore Policlinico and University of Milan, Milan, Italy

Publication History

  1. Published Online: 12 MAY 2011
  2. Published Print: 13 MAY 2011

ISBN Information

Print ISBN: 9780470670576

Online ISBN: 9781119979401



  • hemophilia;
  • inhibitors;
  • therapy;
  • bypassing agents;
  • unresponsive hemorrhage;
  • sequential combined therapy;
  • recombinant factor FVIIa;
  • activated prothrombin complex concentrate


Bleeding events in patients with hemophilia and high-responding inhibitors are to be treated with bypassing agents, namely recombinant factor VIIa (rFVIIa) and activated prothrombin complex concentrates (APCC). They have been shown to be effective in about 80–90% of bleeding events. The remaining 10–20% cannot be controlled by them, with a consequent life- and limb-threat, acute and chronic severe pain and a huge consumption of economic and human resources. Recently, the sequential combination of the two major bypassing agents has been reported to be successful in the management of problem bleeding in non-responders. This chapter reviews the available in vitro and in vivo findings on efficacy of bypassing agents in combination.