Parameters influencing FVIII pharmacokinetics in patients with severe and moderate haemophilia A

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Parameters influencing FVIII pharmacokinetics in patients with severe and moderate haemophilia AS. Kepa1, B. Horvath2, S. Reitter-Pfoertner1, M. Schemper3, P. Quehenberger2, M. Grundbichler4, M. Heistinger5, P. Neumeister6, C. Mannhalter2 andI. Pabinger1,*Article first published online: 13 JAN 2015

DOI: 10.1111/hae.12592

© 2014 John Wiley & Sons Ltd

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HaemophiliaEarly View (Online Version of Record published before inclusion in an issue)

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How to CiteKepa, S., Horvath, B., Reitter-Pfoertner, S., Schemper, M., Quehenberger, P., Grundbichler, M., Heistinger, M., Neumeister, P., Mannhalter, C. and Pabinger, I. (2015), Parameters influencing FVIII pharmacokinetics in patients with severe and moderate haemophilia A. Haemophilia. doi: 10.1111/hae.12592

Author Information1

Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria

2

Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria

3

Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria

4

Division of Haematology and Oncology, Department of Internal Medicine III, Medical University of Salzburg, Salzburg, Austria

5

Department of Internal Medicine I, Clinical Centre of Klagenfurt am Woerthersee, Klagenfurt am Woerthersee, Austria

6

Division of Haematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

* Correspondence: Ingrid Pabinger, Medical University of Vienna, Department of Medicine I, Clinical Division of Haematology and Haemostaseology, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Tel.: +43 1 40400 44480; fax: +43 1 4040027430;
e-mail: ingrid.pabinger@meduniwien.ac.at

Publication HistoryArticle first published online: 13 JAN 2015Manuscript Accepted: 24 OCT 2014Funded byAustrian Haemophilia Society SEARCH Search Scope All contentPublication titlesIn this journalIn this issue Search String Advanced >Saved Searches > SEARCH BY CITATION Volume: Issue: Page: ARTICLE TOOLSGet PDF (268K)Save to My ProfileE-mail Link to this ArticleExport Citation for this ArticleGet Citation AlertsRequest Permissions AbstractArticleReferencesCited By View Full Article (HTML) Enhanced Article (HTML) Get PDF (268K) Keywords:Haemophilia A;influences on FVIII pharmacokinetics;LRP1;LRP1 polymorphisms;Protein CSummary

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.

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