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Monitoring rFVIIa 90 μg kg −1 dosing in haemophiliacs: comparing laboratory response using various whole blood assays over 6 h
Author(s) -
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.,
EZBAN M.,
HEDNER U.
Publication year - 2011
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/j.1365-2516.2011.02492.x
Subject(s) - medicine , dosing , whole blood , pharmacology , surgery
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.