The function of factor VIIa in hemophilia A: An hypothesis

  • Yale Nemerson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 386)


Since accepting the assignment to talk about this subject, I have reminded myself that I informed my host I hadn’t the slightest idea of how Factor Vila functions in hemophilia! This disclaimer notwithstanding, I do have an hypothesis, albeit one with no experimental validation nor any particular intellectual appeal. It is simply that the activation of Factor VII (F.VII) in vivo is the rate-limiting step in hemostasis, at least in hemophiliacs. I will discuss this concept below.


Tissue Factor Tissue Factor Pathway Inhibitor VIla Level Phospholipid Vesicle Wall Shear Rate 
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  1. 1.
    Macik, B.G., et al., 1993, Safety and initial clinical efficacy of three dose levels of recombinant activated RVII (rFVIIa): Results of a phase I study, Blood Coagul Fibrinolysis. 4: 521 – 527.PubMedCrossRefGoogle Scholar
  2. 2.
    Silverberg, S.A., Nemerson, Y. and Zur, M., 1977, Kinetics of the activation of bovine coagulation factor X by components of the extrinsic pathway. Kinetic behavior of two-chain F.VII in the presence and absence of tissue factor, J.Biol.Chem.252: 8481 – 8488.PubMedGoogle Scholar
  3. 3.
    Bach, R., Gentry, R. and Nemerson, Y, 1986, F.VII binding to tissue factor in reconstituted phospholipid vesicles: Induction of cooperativity by phosphatidylserine, Biochem. 25: 4007 – 4020.CrossRefGoogle Scholar
  4. 4.
    Neuenschwander, P.F., Fiore, M.M. and Morrissey, J.H., 1993, F.VII autoactivation proceeds via interaction of distinct protease-cofactor and zymogen-cofactor complexes, J.Biol.Chem.268: 21489 – 21492.PubMedGoogle Scholar
  5. 5.
    Eisinger, J., Flores, J. and Petersen, W.P., 1986, A milling crowd model for local and long-range obstructed lateral diffusion, Biophys J. 49: 987 – 1001.PubMedCrossRefGoogle Scholar
  6. 6.
    Sassaroli, M., Vauhkonen,M., Perry, D. and Eisinger J.r 1990, Lateral diffusivity of lipid analogue excimeric probes in dimyristoylphosphatidylcholine bilayers, Biophys. J, 57: 281 – 290.Google Scholar
  7. 7.
    Wildgoose, P., et al., 1992, Measurement of basal levels of F.VIIa in hemophilia A and B patients, Bloodd’80: 25–28.Google Scholar
  8. 8.
    Andree, H.A.M., Contino, P.B., Repke, D., Gentry, R. and Nemerson, Y, 1994, Transport rate-limited catalysis on macroscopic surfaces: The activation of Factor X in a continuous flow enzyme reactor, Biochem. 33: 4368 – 4374.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1995

Authors and Affiliations

  • Yale Nemerson
    • 1
  1. 1.Department of Biochemistry and Division of Molecular Medicine, Department of MedicineMount Sinai School of Medicine of the City University of New YorkNew YorkUSA

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