Blood Journal
Leading the way in experimental and clinical research in hematology

Thrombin generation and whole blood viscoelastic assays in the management of hemophilia: current state of art and future perspectives

  1. Guy Young1,
  2. Benny Sørensen2,3,4,
  3. Yesim Dargaud5,
  4. Claude Negrier5,
  5. Kathleen Brummel-Ziedins6, and
  6. Nigel S. Key7
  1. 1Children’s Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA;
  2. 2Haemostasis Research Unit, Center for Haemostasis and Thrombosis, Guy’s and St Thomas’ Foundation Trust, London, United Kingdom;
  3. 3King’s College London School of Medicine, London, United Kingdom;
  4. 4Centre for Haemophilia and Thrombosis, Aarhus University Hospital, Skejby, Denmark;
  5. 5Unite d’Hemostase Clinique, Hopital Edouard Herriot Lyon, University of Lyon 1, Lyon, France;
  6. 6Department of Biochemistry, University of Vermont, Colchester, VT; and
  7. 7Department of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, NC


Hemophilia is a bleeding disorder that afflicts about 1 in 5000 males. Treatment relies upon replacement of the deficient factor, and response to treatment both in clinical research and practice is based upon subjective parameters such as pain and joint mobility. Existing laboratory assays quantify the amount of factor in plasma, which is useful diagnostically and prognostically. However, these assays are limited in their ability to fully evaluate the patient’s clot-forming capability. Newer assays, known as global assays, provide a far more detailed view of thrombin generation and clot formation and have been studied in hemophilia for about 10 years. They have the potential to offer a more objective measure of both the hemophilic phenotype as well as the response to treatment. In particular, in patients who develop inhibitors to deficient clotting factors and in whom bypassing agents are required for hemostasis, these assays offer the opportunity to determine the laboratory response to these interventions where traditional coagulation assays cannot. In this article we review the existing literature and discuss several controversial issues surrounding the assays. Last, a vision of future clinical uses of these assays is briefly described.

  • Submitted August 21, 2012.
  • Accepted December 30, 2012.
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