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

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 rFVII...

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Autores principales: Altman, Raul, Scazziota, Alejandra, de Lourdes Herrera, Maria, Gonzalez, Claudio D
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885319/
https://www.ncbi.nlm.nih.gov/pubmed/20444280
http://dx.doi.org/10.1186/1477-9560-8-8
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author Altman, Raul
Scazziota, Alejandra
de Lourdes Herrera, Maria
Gonzalez, Claudio D
author_facet Altman, Raul
Scazziota, Alejandra
de Lourdes Herrera, Maria
Gonzalez, Claudio D
author_sort Altman, Raul
collection PubMed
description 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 AUCo→(35 min )were obtained in PPP. The addition of rFVIIa increased the effect of TF in shorting the LT and increasing the AUCo→(35 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.
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spelling pubmed-28853192010-06-15 The hemostatic profile of recombinant activated factor VII. Can low concentrations stop bleeding in off-label indications? Altman, Raul Scazziota, Alejandra de Lourdes Herrera, Maria Gonzalez, Claudio D Thromb J Latest therapeutic developments 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 AUCo→(35 min )were obtained in PPP. The addition of rFVIIa increased the effect of TF in shorting the LT and increasing the AUCo→(35 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. BioMed Central 2010-05-05 /pmc/articles/PMC2885319/ /pubmed/20444280 http://dx.doi.org/10.1186/1477-9560-8-8 Text en Copyright ©2010 Altman et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Latest therapeutic developments
Altman, Raul
Scazziota, Alejandra
de Lourdes Herrera, Maria
Gonzalez, Claudio D
The hemostatic profile of recombinant activated factor VII. Can low concentrations stop bleeding in off-label indications?
title The hemostatic profile of recombinant activated factor VII. Can low concentrations stop bleeding in off-label indications?
title_full The hemostatic profile of recombinant activated factor VII. Can low concentrations stop bleeding in off-label indications?
title_fullStr The hemostatic profile of recombinant activated factor VII. Can low concentrations stop bleeding in off-label indications?
title_full_unstemmed The hemostatic profile of recombinant activated factor VII. Can low concentrations stop bleeding in off-label indications?
title_short The hemostatic profile of recombinant activated factor VII. Can low concentrations stop bleeding in off-label indications?
title_sort hemostatic profile of recombinant activated factor vii. can low concentrations stop bleeding in off-label indications?
topic Latest therapeutic developments
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885319/
https://www.ncbi.nlm.nih.gov/pubmed/20444280
http://dx.doi.org/10.1186/1477-9560-8-8
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