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Platelet activity of high-dose factor VIIa is independent of tissue factor.

Publication ,  Journal Article
Monroe, DM; Hoffman, M; Oliver, JA; Roberts, HR
Published in: Br J Haematol
December 1997

High-dose recombinant factor VIIa has been successfully used as therapy for haemophiliacs with inhibitors. The mechanism by which high-dose factor VIIa supports haemostasis is the subject of some controversy. Postulating a mechanism in which activity is dependent on tissue factor at the site of injury explains the localization of activity but not the requirement for high doses. Postulating a mechanism in which factor VIIa acts on available lipid independently of tissue factor explains the requirement for high doses but not the lack of systemic procoagulant activity. We report that factor VIIa bound weakly to activated platelets (Kd approximately 90 nM). This factor VIIa was functionally active and could initiate thrombin generation in the presence of plasma concentrations of prothrombin, factor X, factor V, antithrombin III and tissue factor pathway inhibitor. The activity was not dependent on tissue factor. The concentration of factor VIIa required for detectable thrombin generation agreed well with the lowest concentration of factor VIIa required for efficacy in patients. High-dose factor VIIa may function on the activated platelets that form the initial haemostatic plug in haemophilic patients. These observations are in agreement with clinical trials which have shown that high-dose factor VIIa was haemostatically effective without causing systemic activation of coagulation.

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Published In

Br J Haematol

DOI

ISSN

0007-1048

Publication Date

December 1997

Volume

99

Issue

3

Start / End Page

542 / 547

Location

England

Related Subject Headings

  • Thromboplastin
  • Thrombin
  • Platelet Activation
  • Immunology
  • Humans
  • Fluorescent Antibody Technique
  • Factor Xa
  • Factor VIIa
  • Blood Platelets
  • 3201 Cardiovascular medicine and haematology
 

Citation

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Monroe, D. M., Hoffman, M., Oliver, J. A., & Roberts, H. R. (1997). Platelet activity of high-dose factor VIIa is independent of tissue factor. Br J Haematol, 99(3), 542–547. https://doi.org/10.1046/j.1365-2141.1997.4463256.x
Monroe, D. M., M. Hoffman, J. A. Oliver, and H. R. Roberts. “Platelet activity of high-dose factor VIIa is independent of tissue factor.Br J Haematol 99, no. 3 (December 1997): 542–47. https://doi.org/10.1046/j.1365-2141.1997.4463256.x.
Monroe DM, Hoffman M, Oliver JA, Roberts HR. Platelet activity of high-dose factor VIIa is independent of tissue factor. Br J Haematol. 1997 Dec;99(3):542–7.
Monroe, D. M., et al. “Platelet activity of high-dose factor VIIa is independent of tissue factor.Br J Haematol, vol. 99, no. 3, Dec. 1997, pp. 542–47. Pubmed, doi:10.1046/j.1365-2141.1997.4463256.x.
Monroe DM, Hoffman M, Oliver JA, Roberts HR. Platelet activity of high-dose factor VIIa is independent of tissue factor. Br J Haematol. 1997 Dec;99(3):542–547.
Journal cover image

Published In

Br J Haematol

DOI

ISSN

0007-1048

Publication Date

December 1997

Volume

99

Issue

3

Start / End Page

542 / 547

Location

England

Related Subject Headings

  • Thromboplastin
  • Thrombin
  • Platelet Activation
  • Immunology
  • Humans
  • Fluorescent Antibody Technique
  • Factor Xa
  • Factor VIIa
  • Blood Platelets
  • 3201 Cardiovascular medicine and haematology