Monitoring rFVIIa 90 μg kg(-1) dosing in haemophiliacs: comparing laboratory response using various whole blood assays over 6 h.
(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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https://lup.lub.lu.se/record/1884514
- author
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- thromboelastography, thrombin generation, ROTEM, haemophilia, Hemodyne, platelets
- in
- Haemophilia
- volume
- 17
- issue
- 5
- pages
- 949 - 957
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000294174300026
- pmid:21362113
- scopus:80052036683
- pmid:21362113
- ISSN
- 1351-8216
- DOI
- 10.1111/j.1365-2516.2011.02492.x
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Emergency medicine/Medicine/Surgery (013240200)
- id
- e857863b-dfff-4e55-934a-7cb362ad50b0 (old id 1884514)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21362113?dopt=Abstract
- date added to LUP
- 2016-04-01 10:26:23
- date last changed
- 2022-06-30 02:06:33
@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 < 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.}},
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}},
keywords = {{thromboelastography; thrombin generation; ROTEM; haemophilia; Hemodyne; platelets}},
language = {{eng}},
number = {{5}},
pages = {{949--957}},
publisher = {{Wiley-Blackwell}},
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}},
doi = {{10.1111/j.1365-2516.2011.02492.x}},
volume = {{17}},
year = {{2011}},
}