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- Title
Parameters influencing FVIII pharmacokinetics in patients with severe and moderate haemophilia A.
- Authors
Kepa, S.; Horvath, B.; Reitter‐Pfoertner, S.; Schemper, M.; Quehenberger, P.; Grundbichler, M.; Heistinger, M.; Neumeister, P.; Mannhalter, C.; Pabinger, I.
- Abstract
In haemophilia A patients factor VIII ( FVIII) recovery and half-life can vary substantially. There are parameters known to modulate FVIII pharmacokinetics ( PK), but they explain only about 34% of the variability. The aim of this study was to identify new parameters that influence FVIII PK and thus to expand the current knowledge. FVIII PK were determined in 42 haemophilia A patients (37 severe, 5 moderate) without inhibitor. Patients' characteristics and laboratory parameters were evaluated for an association with FVIII PK. We analysed plasma levels of low-density lipoprotein receptor-related protein 1 ( LRP1) and protein C ( PC) activity, which had been hypothesized to influence FVIII activity. Furthermore, four variations in intron 6 of the LRP1 gene, which had been shown to influence LRP1, were investigated. FVIII half-life differed widely from 6.2 to 20.7 h, with a median of 10.0 h. Patients with blood group O had shorter FVIII half-life compared to patients with non-O blood group (median FVIII half-life 9.0 h vs. 10.4 h, P = 0.018). Age was significantly associated with FVIII half-life ( r = 0.32, P = 0.035). Besides age, also VWF antigen ( r = 0.52, P < 0.001) and blood group ( r = −0.37, P = 0.015) was associated with FVIII half-life. No correlation was found with FVIII- or LRP1-genotype, LRP1 or PC concentrations. Our data showed large differences in FVIII PK between individual patients and revealed age, blood group and VWF levels as important determining factors for FVIII half-life. FVIII genotype or levels of LRP1 or PC had no influence on FVIII PK.
- Subjects
PHARMACOKINETICS; HEMOPHILIACS; CHEMICAL inhibitors; LOW density lipoproteins; PROTEIN C; STATISTICAL correlation
- Publication
Haemophilia, 2015, Vol 21, Issue 3, p343
- ISSN
1351-8216
- Publication type
Article
- DOI
10.1111/hae.12592