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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:10.)
© 2003 American Heart Association, Inc.

Editorials

Response: Mechanism of Action of High-Dose Factor VIIa

Kenneth G. Mann; Saulius Butenas

From the Department of Biochemistry, University of Vermont, Burlington.

Correspondence to Kenneth G. Mann, Department of Biochemistry, University of Vermont, C-401 Given Bldg, 89 Beaumont Ave, Burlington, VT 05405-0068. E-mail kmann@zoo.uvm.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

There are two areas of disagreement between our groups concerning the mechanism of action of supraphysiological factor VIIa concentrations in hemophilia:

1. Whether high concentrations of factor VIIa can support vigorous thrombin generation in the absence of factor VIII and factor IX in a tissue factor-independent manner.
   
2. Whether phospholipid additions can increase the hemostatic (or thrombotic) potential of the factor VIIa/tissue factor complex.
   

Recombinant factor VIIa at supraphysiological concentrations has been used primarily for the treatment of bleeding episodes related to hemophilia with inhibitors.¹ However, the "standard" dose of 90 µg/kg (26 nmol/L) has also been used for the treatment of a variety of bleeding disorders,¹ leading to reports of either success or failure to provide normal hemostasis.^2–4 These observations emphasize the importance of knowledge related to the mechanism by which supraphysiological concentrations of factor VIIa may act to produce a desirable response.

See pages 8 and 123

Our data using both a synthetic coagulation model (in the presence of either phospholipids or platelets) and minimally altered fresh blood suggest that factor VIIa at the pharmacological concentration attained (10 nmol/L) does not restore normal thrombin generation in hemophilia A and hemophilia B blood.^5,6 However, the addition of anionic phospholipids together with 10 nmol/L factor VIIa to "acquired" hemophilia B blood increases thrombin generation to the extent observed in normal blood at the same tissue factor concentration.⁶

We agree and have reported that the role of platelets in blood coagulation is more complex than that of phospholipids.⁷ However, phospholipid . . . [Full Text of this Article]

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