Abstract
BackgroundVon 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.MethodologyStandardized 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 FindingsFVIII 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%).ConclusionOur 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.
Highlights
The bleeding disorder haemophilia A is caused by defects in the gene encoding coagulation factor VIII and affects 1–2 in 10,000 male births [1]
Our data indicate that survival of factor VIII (FVIII) is determined by survival of endogenous Von Willebrand factor (VWF) rather than VWF levels per se
Average FVIII half-life was significantly shorter in bloodgroup O patients than in non-O patients (11.562.6 h versus 14.363.0 h)
Summary
The bleeding disorder haemophilia A is caused by defects in the gene encoding coagulation factor VIII and affects 1–2 in 10,000 male births [1]. FVIII circulates in a tight non-covalent complex with von Willebrand factor (VWF). The formation of this complex is of physiological importance to maintain appropriate plasma levels of FVIII [2,3]. Since the early 1970s, treatment protocols started to shift from on-demand replacementtherapy in cases of bleeds, towards prophylactic treatment to prevent bleeds This was applied for patients who had already experienced several joint bleeds [5]. Individualization of prophylactic treatment according to half-life may help optimizing treatmentprotocols and improve efficiency of FVIII use. This is of particular relevance in children on prophylaxis, since bleeding is determined by time spent below 1% FVIII activity levels [8]. Since FVIII half-life correlates with VWF-antigen pre-infusion levels, we hypothesized that VWF levels are useful to predict FVIII half-life
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
