TY - JOUR
T1 - von Willebrand Factor and Factor VIII Clearance in Perioperative Hemophilia A Patients
AU - van Moort, Iris
AU - Bukkems, Laura H
AU - Heijdra, Jessica M
AU - Schutgens, Roger E G
AU - Laros-van Gorkom, Britta A P
AU - Nieuwenhuizen, Laurens
AU - van der Meer, Felix J M
AU - Fijnvandraat, Karin
AU - Ypma, Paula
AU - de Maat, Moniek P M
AU - Leebeek, Frank W G
AU - Meijer, Karina
AU - Eikenboom, Jeroen
AU - Mathôt, Ron A A
AU - Cnossen, Marjon H
N1 - Funding Information:
This study is part of the research program of the international multicenter OPTI-CLOT consortium (Patient tailOred PharmacokineTIc-guided dosing of CLOTting factor concentrate and DDAVP in bleeding disorders), which aims to implement PK-guided dosing of clotting factor replacement therapy by initiating studies that emphasize the impact of PK-guided dosing, by constructing prophylactic and on-demand dosing population PK models, and by evaluating cost-effectiveness of a PK-guided approach. This specific project was funded by an investigator-initiated research grant from the Dutch Research Institute NWO-ZonMW with co-financing by Baxter. A complete list of OPTI-CLOT research program members is available in the ►Supplementary Material (available in the online version).
Publisher Copyright:
© 2020 Georg Thieme Verlag. All rights reserved.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - 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.
AB - 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.
KW - factor VIII
KW - hemophilia A
KW - linear mixed effect modeling
KW - postsurgical bleeding
KW - surgery
KW - von Willebrand factor
UR - https://www.scopus.com/pages/publications/85087877048
U2 - 10.1055/s-0040-1710591
DO - 10.1055/s-0040-1710591
M3 - Article
C2 - 32480417
SN - 0340-6245
VL - 120
SP - 1056
EP - 1065
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
IS - 07
ER -