von Willebrand Factor and Factor VIII Clearance in Perioperative Hemophilia A Patients.

BACKGROUND

 von Willebrand factor (VWF) is crucial for optimal dosing of factor VIII (FVIII) concentrate in hemophilia A patients as it protects FVIII from premature clearance. To date, it is unknown how VWF behaves and what its impact is on FVIII clearance in the perioperative setting.

AIM

 To investigate VWF kinetics (VWF antigen [VWF:Ag]), VWF glycoprotein Ib binding (VWF:GPIbM), and VWF propeptide (VWFpp) in severe and moderate perioperative hemophilia A patients included in the randomized controlled perioperative OPTI-CLOT trial.

METHODS

 Linear mixed effects modeling was applied to analyze VWF kinetics. One-way and two-way analyses of variance were used to investigate perioperative VWFpp/VWF:Ag ratios and associations with surgical bleeding.

RESULTS

 Fifty-nine patients with median age of 48.8 years (interquartile range: 34.8-60.0) were included. VWF:Ag and VWF:GPIbM increased significantly postoperatively. Blood type non-O or medium risk surgery were associated with higher VWF:Ag and VWF:GPIbM levels compared with blood type O and low risk surgery. VWFpp/VWF:Ag was significantly higher immediately after surgery than 32 to 57 hours after surgery (

CONCLUSION

 VWF:Ag and VWF:GPIbM levels increase postoperatively, most significantly in patients with blood type non-O or medium risk surgery. Lower VWF antigen levels did not lead to clinically relevant higher FVIII clearance. VWF:Ag or VWF:GPIbM levels were not associated with perioperative hemorrhage.

Informations de copyright

Georg Thieme Verlag KG Stuttgart · New York.

Déclaration de conflit d'intérêts

R.E.G. Schutgens has received research support from CSL Behring and Sanquin. B. Laros-van Gorkom has received unrestricted educational grants from Baxter and CSL Behring. F. J. M. van der Meer received grants from Bayer, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Sanquin, and Sobi for the development of a registry of Hemophilia patients in the Netherlands (HemoNED). K. Fijnvandraat is a member of the European Hemophilia Treatment and Standardization Board sponsored by Baxalta, has received unrestricted research grants from CSL Behring, Pfizer, and Bayer, and has given lectures at educational symposiums organized by Pfizer, Baxalta, Novonordisk, and Bayer. F.W.G. Leebeek received research support from CSL Behring and Shire for performing the Willebrand in the Netherlands (WiN) study, and is consultant for UniQure, Novo Nordisk, and Shire, of which the fees go to the institution. He is a member of the DSMB for a study of Roche. K. Meijer received research support from Bayer, Sanquin, and Pfizer; speaker fees from Bayer, Sanquin, Boehringer Ingelheim, BMS, and Aspen; consulting fees from UniQure (all fees go to the institution). Moniek P.M. de Maat received speaker fees and unconditional research contributions from Werfen, Siemens, Roche, and Stago. J. Eikenboom reports receiving research grants from CSL Behring and honorarium for educational activities from Roche and Celgene. R.A.A. Mathôt has served as advisor for Bayer, CSL Behring, Merck Sharp & Dohme, Shire, and Zeria (all honoraria/fees paid to the department); He has received unrestricted research grants from Bayer, CSL Behring, and Shire. M. H. Cnossen has received grants from governmental research institutes such as Dutch Research Institute (NWO), ZonMW, Innovation fund, NWO-NWA, and unrestricted investigator initiated research grants as well as educational and travel funding from the following companies over the years: Pfizer, Baxter/ Baxalta/ Shire/ Takeda, Bayer Schering Pharma, CSL Behring, Sobi Biogen, Novo Nordisk, Novartis, and Nordic Pharma, and has served as a member on steering boards of Roche and Bayer. All grants, awards, and fees go to the institution. The remaining authors declare no competing financial interests.