This Article Full Text Full Text (PDF) All Versions of this Article: 23/1/123    most recent 01.ATV.0000042081.57854.A2v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Butenas, S. Articles by Mann, K. G. Search for Related Content PubMed PubMed Citation Articles by Butenas, S. Articles by Mann, K. G. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB LECITHIN Related Collections Lipids Thrombin Platelets Other Research

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:123.)
© 2003 American Heart Association, Inc.

Thrombosis

Influence of Factor VIIa and Phospholipids on Coagulation in "Acquired" Hemophilia

Saulius Butenas; Kathleen E. Brummel; Sara G. Paradis; Kenneth G. Mann

From the University of Vermont, College of Medicine, Burlington, Vt.

Correspondence to Kenneth G. Mann, Department of Biochemistry, University of Vermont, Given Building, Room C401, 89 Beaumont Ave, Burlington, VT 05405-0068. E-mail kmann{at}zoo.uvm.edu

Objective— This study was performed to evaluate the influences of phospholipids and recombinant factor VIIa (rFVIIa) on thrombin generation and clot formation in "acquired" hemophilia B.

Methods and Results— A synthetic mixture corresponding to hemophilia A (SHA) and "acquired" hemophilia B blood (AHBB) manufactured in vitro by an anti-FIX antibody were used in this study. With 10 pmol/L tissue factor (TF), 10 nmol/L rFVIIa, and saturating phospholipid, established thrombin generation in SHA was similar to that observed in the presence of factor VIII and rFVIIa at physiological concentrations. At lower phospholipid concentrations, thrombin generation was delayed and reduced. With 5 pmol/L TF, contact pathway-inhibited AHBB clotted later than normal blood and showed reduced clot stability and thrombin generation. These parameters of effectiveness were increased by the addition of phospholipids to AHBB, which restored clot stability and increased thrombin generation. No correction of clot formation or thrombin generation was observed when rFVIIa and phospholipids were added to AHBB in the absence of TF.

Conclusions— The influence of rFVIIa is dependent on TF, and phospholipids substantially increase the hemostatic (or thrombotic) potential of rFVIIa/TF.

Key Words: hemophilia • factor VIIa • tissue factor • phospholipids • thrombin generation

This article has been cited by other articles:

				T. Orfeo, K. E. Brummel-Ziedins, M. Gissel, S. Butenas, and K. G. Mann The Nature of the Stable Blood Clot Procoagulant Activities J. Biol. Chem., April 11, 2008; 283(15): 9776 - 9786. [Abstract] [Full Text] [PDF]

				O. Warren, K. Mandal, V. Hadjianastassiou, L. Knowlton, S. Panesar, K. John, A. Darzi, and T. Athanasiou Recombinant Activated Factor VII in Cardiac Surgery: A Systematic Review Ann. Thorac. Surg., February 1, 2007; 83(2): 707 - 714. [Abstract] [Full Text] [PDF]

				T. Orfeo, S. Butenas, K. E. Brummel-Ziedins, and K. G. Mann The Tissue Factor Requirement in Blood Coagulation J. Biol. Chem., December 30, 2005; 280(52): 42887 - 42896. [Abstract] [Full Text] [PDF]

				H. R. Roberts, D. M. Monroe, and G. C. White The use of recombinant factor VIIa in the treatment of bleeding disorders Blood, December 15, 2004; 104(13): 3858 - 3864. [Abstract] [Full Text] [PDF]