TITLE

The hemostatic profile of recombinant activated factor VII. Can low concentrations stop bleeding in off-label indications?

AUTHOR(S)
Altman, Raul; Scazziota, Alejandra; de Lourdes Herrera, Maria; Gonzalez, Claudio D.
PUB. DATE
January 2010
SOURCE
Thrombosis Journal;2010, Vol. 8, p8
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: High concentrations of recombinant activated factor VII (rFVIIa) can stop bleeding in hemophilic patients. However the rFVIIa dose needed for stopping haemhorrage in off-label indications is unknown. Since thrombin is the main hemostatic agent, this study investigated the effect of rFVIIa and tissue factor (TF) on thrombin generation (TG) in vitro. Methods: Lag time (LT), time to peak (TTP), peak TG (PTG), and area under the curve after 35 min (AUCo-35 min) with the calibrated automated thrombography was used to evaluate TG. TG was assayed in platelet-rich plasma (PRP) samples from 29 healthy volunteers under basal conditions and after platelet stimulation with 5.0 μg/ml, 2.6 μg/ml, 0.5 μg/ml, 0.25 μg/ml, and 0.125 μg/ml rFVIIa alone and in normal platelet-poor plasma (PPP) samples from 22 healthy volunteers, rFVIIa in combination with various concentrations of TF (5.0, 2.5, 1.25 and 0.5 pM). Results: In PRP activated by rFVIIa, there was a statistically significant increase in TG compared to basal values. A significant TF dose-dependent shortening of LT and increased PTG and AUCoT35 min were obtained in PPP. The addition of rFVIIa increased the effect of TF in shorting the LT and increasing the AUCoT35 min with no effect on PTG but were independent of rFVIIa concentration. Conclusion: Low concentrations of rFVIIa were sufficient to form enough thrombin in normal PRP or in PPP when combined with TF, and suggest low concentrations for normalizing hemostasis in off-label indications.
ACCESSION #
52008496

 

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