Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Kepa, S; Horvath, B; Reitter-Pfoertner, S; Schemper, M; Quehenberger, P; Grundbichler, M; Heistinger, M; Neumeister, P; Mannhalter, C; Pabinger, I.
Parameters influencing FVIII pharmacokinetics in patients with severe and moderate haemophilia A.
Haemophilia. 2015; 21(3):343-350
Doi: 10.1111/hae.12592
Web of Science
PubMed
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- Co-authors Med Uni Graz
- Neumeister Peter
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- 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. © 2014 John Wiley & Sons Ltd.
- Find related publications in this database (using NLM MeSH Indexing)
- ABO Blood-Group System -
- Adult -
- Age Factors -
- Blood Coagulation -
- Body Mass Index -
- Factor VIII - administration & dosage
- Factor VIII - pharmacokinetics
- Factor VIII - therapeutic use
- Half-Life -
- Hemophilia A - blood
- Hemophilia A - diagnosis
- Hemophilia A - drug therapy
- Humans -
- Low Density Lipoprotein Receptor-Related Protein-1 - genetics
- Male -
- Mutation -
- Polymorphism, Single Nucleotide -
- Recombinant Proteins -
- Severity of Illness Index -
- Treatment Outcome -
- Young Adult -
- von Willebrand Factor -
- Find related publications in this database (Keywords)
- Haemophilia A
- influences on FVIII pharmacokinetics
- LRP1
- LRP1 polymorphisms
- Protein C