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Monitoring rFVIIa 90 μg kg(-1) dosing in haemophiliacs: comparing laboratory response using various whole blood assays over 6 h.

Brophy, D F; Martin, E J; Christian Barrett, J; Nolte, M E; Kuhn, J G; Gerk, P M; Carr, M E; Pelzer, H; Agersø, H and Ezban, M, et al. (2011) In Haemophilia 17(5). p.949-957
Abstract
Summary. Recombinant FVIIa is a haemostatic agent administered to patients with severe FVIII or FIX deficiency with inhibitors. Although rFVIIa is effective at stopping bleeding, a reliable assay to monitor its effect is lacking. To characterize the pharmacokinetics and global coagulation effects of rFVIIa for 6 h following a IV dose of 90 μg kg(-1) . Ten non-bleeding subjects with severe FVIII or FIX deficiency were infused with a single-dose of rFVIIa 90 μg kg(-1) body weight and blood was collected before and at 0.5, 1, 2, 4 and 6 h postdose. Global haemostasis was characterized throughout the study utilizing whole blood analyses (Hemodyne HAS, TEG, ROTEM). The clearance and half-life of factor FVII:C was estimated as 39.0 ± 8.8 mL... (More)
Summary. Recombinant FVIIa is a haemostatic agent administered to patients with severe FVIII or FIX deficiency with inhibitors. Although rFVIIa is effective at stopping bleeding, a reliable assay to monitor its effect is lacking. To characterize the pharmacokinetics and global coagulation effects of rFVIIa for 6 h following a IV dose of 90 μg kg(-1) . Ten non-bleeding subjects with severe FVIII or FIX deficiency were infused with a single-dose of rFVIIa 90 μg kg(-1) body weight and blood was collected before and at 0.5, 1, 2, 4 and 6 h postdose. Global haemostasis was characterized throughout the study utilizing whole blood analyses (Hemodyne HAS, TEG, ROTEM). The clearance and half-life of factor FVII:C was estimated as 39.0 ± 8.8 mL h(-1) kg(-1) and 2.1 ± 0.2 h respectively. There was good inter-assay agreement with respect to clot initiation parameters (R, CT and FOT) and these parameters all fell to a mean of approximately 9 min following rFVIIa dosing. The platelet contractile force (PCF) and clot elastic modulus (CEM) were positively correlated to FVII:C (P < 0.0001), and these parameters were dynamic throughout the 6-h period. The MA and MCF did not correlate to FVII:C nor did they significantly change during the study. Prothrombin F1 + 2 significantly increased following rFVIIa dosing (P < 0.001), but remained steady throughout the study. There was no change in D-dimer concentrations over time. The FOT, R and CT characterized clot initiation following rFVIIa dosing. The PCF and CEM were correlated to FVII:C and characterized the dynamics of platelet function and clot strength over the rFVIIa dosing interval. The clinical significance of these findings needs additional study. (Less)
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published
subject
keywords
thromboelastography, thrombin generation, ROTEM, haemophilia, Hemodyne, platelets
in
Haemophilia
volume
17
issue
5
pages
949 - 957
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000294174300026
  • pmid:21362113
  • scopus:80052036683
ISSN
1351-8216
DOI
10.1111/j.1365-2516.2011.02492.x
language
English
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yes
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e857863b-dfff-4e55-934a-7cb362ad50b0 (old id 1884514)
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http://www.ncbi.nlm.nih.gov/pubmed/21362113?dopt=Abstract
date added to LUP
2011-04-01 11:57:19
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2017-11-05 03:12:02
@article{e857863b-dfff-4e55-934a-7cb362ad50b0,
  abstract     = {Summary. Recombinant FVIIa is a haemostatic agent administered to patients with severe FVIII or FIX deficiency with inhibitors. Although rFVIIa is effective at stopping bleeding, a reliable assay to monitor its effect is lacking. To characterize the pharmacokinetics and global coagulation effects of rFVIIa for 6 h following a IV dose of 90 μg kg(-1) . Ten non-bleeding subjects with severe FVIII or FIX deficiency were infused with a single-dose of rFVIIa 90 μg kg(-1) body weight and blood was collected before and at 0.5, 1, 2, 4 and 6 h postdose. Global haemostasis was characterized throughout the study utilizing whole blood analyses (Hemodyne HAS, TEG, ROTEM). The clearance and half-life of factor FVII:C was estimated as 39.0 ± 8.8 mL h(-1) kg(-1) and 2.1 ± 0.2 h respectively. There was good inter-assay agreement with respect to clot initiation parameters (R, CT and FOT) and these parameters all fell to a mean of approximately 9 min following rFVIIa dosing. The platelet contractile force (PCF) and clot elastic modulus (CEM) were positively correlated to FVII:C (P &lt; 0.0001), and these parameters were dynamic throughout the 6-h period. The MA and MCF did not correlate to FVII:C nor did they significantly change during the study. Prothrombin F1 + 2 significantly increased following rFVIIa dosing (P &lt; 0.001), but remained steady throughout the study. There was no change in D-dimer concentrations over time. The FOT, R and CT characterized clot initiation following rFVIIa dosing. The PCF and CEM were correlated to FVII:C and characterized the dynamics of platelet function and clot strength over the rFVIIa dosing interval. The clinical significance of these findings needs additional study.},
  author       = {Brophy, D F and Martin, E J and Christian Barrett, J and Nolte, M E and Kuhn, J G and Gerk, P M and Carr, M E and Pelzer, H and Agersø, H and Ezban, M and Hedner, Ulla},
  issn         = {1351-8216},
  keyword      = {thromboelastography,thrombin generation,ROTEM,haemophilia,Hemodyne,platelets},
  language     = {eng},
  number       = {5},
  pages        = {949--957},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {Haemophilia},
  title        = {Monitoring rFVIIa 90 μg kg(-1) dosing in haemophiliacs: comparing laboratory response using various whole blood assays over 6 h.},
  url          = {http://dx.doi.org/10.1111/j.1365-2516.2011.02492.x},
  volume       = {17},
  year         = {2011},
}