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High dose factor VIIa improves clot structure and stability in a model of haemophilia B.

Publication ,  Journal Article
Wolberg, AS; Allen, GA; Monroe, DM; Hedner, U; Roberts, HR; Hoffman, M
Published in: Br J Haematol
December 2005

Factor IX (FIX) deficiency results in haemophilia B and high dose recombinant activated factor VII (rFVIIa) can decrease bleeding. Previously, we showed that FIX deficiency results in a reduced rate and peak of thrombin generation. We have now used plasma and an in vitro coagulation model to examine the effect of these changes in thrombin generation on fibrin clot structure and stability. Low FIX delayed the clot formation onset and reduced the fibrin polymerisation rate. Clots formed without FIX were composed of thicker fibrin fibres than normal. rFVIIa shortened the clot formation onset time and improved the fibre structure of haemophilic clots. We also examined clot formation in the presence of a fibrinolytic challenge by including tissue plasminogen activator or plasmin in the reaction milieu. In these assays, normal FIX levels supported clot formation; however, clots did not form in the absence of FIX. rFVIIa partially restored haemophilic clot formation. These results were independent of the effects of the thrombin-activatable fibrinolysis inhibitor. Our data suggest that rFVIIa enhances haemostasis in haemophiliacs by increasing the thrombin generation rate to both promote formation of a structurally normal clot and improve clot formation and stability at sites with high endogenous fibrinolytic activities.

Duke Scholars

Published In

Br J Haematol

DOI

ISSN

0007-1048

Publication Date

December 2005

Volume

131

Issue

5

Start / End Page

645 / 655

Location

England

Related Subject Headings

  • Tissue Plasminogen Activator
  • Thrombin
  • Recombinant Proteins
  • Nephelometry and Turbidimetry
  • Microscopy, Electron, Scanning
  • Immunology
  • Humans
  • Hemostatics
  • Hemostasis
  • Hemophilia B
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wolberg, A. S., Allen, G. A., Monroe, D. M., Hedner, U., Roberts, H. R., & Hoffman, M. (2005). High dose factor VIIa improves clot structure and stability in a model of haemophilia B. Br J Haematol, 131(5), 645–655. https://doi.org/10.1111/j.1365-2141.2005.05820.x
Wolberg, Alisa S., Geoffrey A. Allen, Dougald M. Monroe, Ulla Hedner, Harold R. Roberts, and Maureane Hoffman. “High dose factor VIIa improves clot structure and stability in a model of haemophilia B.Br J Haematol 131, no. 5 (December 2005): 645–55. https://doi.org/10.1111/j.1365-2141.2005.05820.x.
Wolberg AS, Allen GA, Monroe DM, Hedner U, Roberts HR, Hoffman M. High dose factor VIIa improves clot structure and stability in a model of haemophilia B. Br J Haematol. 2005 Dec;131(5):645–55.
Wolberg, Alisa S., et al. “High dose factor VIIa improves clot structure and stability in a model of haemophilia B.Br J Haematol, vol. 131, no. 5, Dec. 2005, pp. 645–55. Pubmed, doi:10.1111/j.1365-2141.2005.05820.x.
Wolberg AS, Allen GA, Monroe DM, Hedner U, Roberts HR, Hoffman M. High dose factor VIIa improves clot structure and stability in a model of haemophilia B. Br J Haematol. 2005 Dec;131(5):645–655.
Journal cover image

Published In

Br J Haematol

DOI

ISSN

0007-1048

Publication Date

December 2005

Volume

131

Issue

5

Start / End Page

645 / 655

Location

England

Related Subject Headings

  • Tissue Plasminogen Activator
  • Thrombin
  • Recombinant Proteins
  • Nephelometry and Turbidimetry
  • Microscopy, Electron, Scanning
  • Immunology
  • Humans
  • Hemostatics
  • Hemostasis
  • Hemophilia B