Models for prediction of factor VIII half-life in severe haemophiliacs: distinct approaches for blood group O and non-O patients.

Abstract

BACKGROUND:

Von Willebrand factor (VWF) is critical for the in vivo survival of factor VIII (FVIII). Since FVIII half-life correlates with VWF-antigen pre-infusion levels, we hypothesized that VWF levels are useful to predict FVIII half-life.

METHODOLOGY:

Standardized half-life studies and analysis of pre-infusion VWF and VWF-propeptide levels were performed in a cohort of 38 patients with severe haemophilia A (FVIII <1 IU/ml), aged 15-44 years. Nineteen patients had blood-group O. Using multivariate linear regression-analysis (MVLR-analysis), the association of VWF-antigen, VWF-propeptide, age and body-weight with FVIII half-life was evaluated.

PRINCIPAL FINDINGS:

FVIII half-life was shorter in blood-group O-patients compared to non-O-patients (11.5+/-2.6 h versus 14.3+/-3.0 h; p = 0.004). VWF-antigen levels correlated with FVIII half-life considerably better in patients with blood-group non-O than O (Pearson-rank = 0.70 and 0.47, respectively). Separate prediction models evolved from MVLR-analysis for blood-group O and non-O patients, based on VWF-antigen and VWF/propeptide ratio. Predicted half-lives deviated less than 3 h of observed half-life in 34/38 patients (89%) or less than 20% in 31/38 patients (82%).

CONCLUSION:

Our approach may identify patients with shorter FVIII half-lives, and adapt treatment protocols when half-life studies are unavailable. In addition, our data indicate that survival of FVIII is determined by survival of endogenous VWF rather than VWF levels per se.

• Authors: Kathelijn Fischer, Ronan Pendu, Carina J van Schooten, Karin van Dijk, Cécile V Denis, H Marijke van den Berg, Peter J Lenting
• Journal: PloS one (PLoS One) Vol. 4 Issue 8 Pg. e6745 (Aug 25 2009) ISSN: 1932-6203 [Electronic] United States
• PMID: 19707594 (Publication Type: Journal Article)

Chemical References

• ABO Blood-Group System
• von Willebrand Factor
• Factor VIII

Topics

• ABO Blood-Group System
• Adolescent
• Adult
• Animals
• Cohort Studies
• Factor VIII (metabolism)
• Half-Life
• Hemophilia A (blood)
• Humans
• Mice
• Mice, Inbred C57BL
• Middle Aged
• Young Adult
• von Willebrand Factor (immunology)