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

Thromb Haemost. 2020 Jul;120(7):1056-1065. doi: 10.1055/s-0040-1710591. Epub 2020 Jun 1.

Abstract

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 bleeding F(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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Blood Loss, Surgical / prevention & control*
  • Drug Administration Schedule
  • Drug Dosage Calculations
  • Factor VIII / administration & dosage
  • Factor VIII / adverse effects
  • Factor VIII / pharmacokinetics*
  • Hemophilia A / blood
  • Hemophilia A / diagnosis
  • Hemophilia A / drug therapy*
  • Hemostatics / administration & dosage
  • Hemostatics / adverse effects
  • Hemostatics / pharmacokinetics*
  • Humans
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Netherlands
  • Perioperative Care
  • Postoperative Hemorrhage / prevention & control*
  • Treatment Outcome
  • von Willebrand Factor / metabolism*

Substances

  • Hemostatics
  • von Willebrand Factor
  • F8 protein, human
  • Factor VIII