Interaction between VWF and FVIII in treating VWD

Abstract

In patients with von Willebrand disease (VWD), the absence of von Willebrand factor (VWF) antigen leads to the premature loss of endogenous circulating secreted factor VIII (FVIII), thereby resulting in the dual defect in haemostasis. Consequently, correcting the VWF deficiency also acts to correct the associated defect in FVIII activity because exogenous VWF forms complexes with and protects endogenous FVIII. The purpose of this study was to summarise relevant aspects of the interaction between VWF and FVIII and to analyse their effects on VWD treatment. Differences in the VWF/FVIII ratios in coagulation factor concentrates should be considered when treating VWD.

circ_0001274 Competitively Binds miR-143-3p to Upregulate VWF Expression to Improve Acute Traumatic Coagulopathy

“…In addition, the premature loss of FVIII caused by the VWF deficiency may induce the dual defect in haemostasis in the patients with von Willebrand disease (VWD). Hence, targeting the VWF deficiency may aid in the protection against VWD through correcting the associated defect in FVIII activity [ 34 ]. More recently, an imbalance of VWF/ADAMTS13 is demonstrated to correlate with poor outcome and bleeding [ 35 ].…”

One piece of the puzzle: Population pharmacokinetics of FVIII during perioperative Haemate P®/Humate P® treatment in von Willebrand disease patients

“…The interaction between VWF and FVIII is complex, considering the variations in the VWF‐interactive region located on the light chain of FVIII and possible underlying genetic mutations . Since VWF acts as a chaperone for FVIII, the observed effect of higher VWF:Act levels resulting in decreased FVIII clearances seems logical .…”

Analysis of current perioperative management with Haemate® P/Humate P® in von Willebrand disease: Identifying the need for personalized treatment

“…4 Although clinical symptoms are generally milder than in haemophilia, dosing of perioperative treatment in VWD is more challenging due to variation in VWD types and mutations, 2,5 interpatient variability of residual endothelial VWF production, VWF secretion and clearance, as well as heterogeneity in types of factor concentrates with different ratios of VWF:Act/FVIII and VWF:Act/VWF antigen (VWF:Ag). 6,7 Previous studies have, however, reported that surgical procedures can be performed safely in patients with VWD and that treatment with VWF-containing concentrates is efficacious. [8][9][10][11][12][13][14][15][16][17] In many countries, specific target levels are defined in national guidelines to safeguard haemostasis during surgery.…”