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

Opti-Clot Study Grp, Iris van Moort, Laura H. Bukkems, Jessica M. Heijdra, Roger E. G. Schutgens, Britta A. P. Laros-van Gorkom, Laurens Nieuwenhuizen, Felix J. M. van der Meer, Karin Fijnvandraat, Paula Ypma, Moniek P. M. de Maat, FrankW. G. Leebeek, Karina Meijer, Jeroen Eikenboom, Ron A. A. Mathot, Marjon H. Cnossen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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 (p <0.001). Lowest VWF:Ag quartile (0.43-0.92 IU/mL) was associated with an increase of FVIII concentrate clearance of 26 mL/h (95% confidence interval: 2-50 mL/h) compared with highest VWF antigen quartile (1.70-3.84 IU/mL). VWF levels were not associated with perioperative bleedingF(4,227) = 0.54,p = 0.710. 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.

Original languageEnglish
Pages (from-to)1056-1065
Number of pages10
JournalThrombosis and Haemostasis
Issue number07
Publication statusPublished - 1-Jul-2020


  • hemophilia A
  • von Willebrand factor
  • surgery
  • factor VIII
  • linear mixed effect modeling
  • postsurgical bleeding

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