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


METHODS
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.


RESULTS
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%).


CONCLUSIONS
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.
Fischer
Kathelijn
K
Van Creveldkliniek, Department of Haematology, University Medical Center Utrecht, Utrecht, the Netherlands.
Pendu
Ronan
R
van Schooten
Carina J
CJ
van Dijk
Karin
K
Denis
Cécile V
CV
van den Berg
H Marijke
HM
Lenting
Peter J
PJ
D000017:ABO Blood-Group System; D000293:Adolescent; D000328:Adult; D000818:Animals; D015331:Cohort Studies; D005169:Factor VIII / Q000378:metabolism*; D006207:Half-Life; D006467:Hemophilia A / Q000097:blood*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D055815:Young Adult; D014841:von Willebrand Factor / Q000276:immunology
D000017:ABO Blood-Group System; D014841:von Willebrand Factor; D005169:Factor VIII
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