The factor VIII/von Willebrand factor complex: basic and clinical issues.

Area of Science:

• Hematology
• Biochemistry
• Molecular Biology

Background:

• Factor VIII (FVIII) and von Willebrand factor (VWF) are essential glycoproteins forming a complex crucial for hemostasis.
• Deficiencies in FVIII/VWF cause inherited bleeding disorders: hemophilia A (HA) and von Willebrand disease (VWD).
• VWF plays a dual role in platelet adhesion and acts as the carrier for FVIII.

Purpose of the Study:

• To elucidate the molecular mechanisms of FVIII/VWF interactions and their significance in hemostasis.
• To review the classification, safety, and clinical application of plasma-derived FVIII/VWF concentrates.
• To highlight the role of the FVIII/VWF complex in replacement therapy for HA and VWD.

Main Methods:

• Review of biochemical investigations on FVIII/VWF interactions.
• Analysis of FVIII/VWF concentrate purification categories and safety factors (viral load reduction, inactivation).
• Examination of clinical guidelines for FVIII/VWF concentrate use in HA and VWD.

Main Results:

• VWF is confirmed as a key partner for FVIII, influencing its function, production, stabilization, conformation, and immunogenicity.
• Plasma-derived FVIII/VWF concentrates, particularly intermediate-high purity ones, offer low risk of infection due to viral inactivation.
• These concentrates are effective for type 3 VWD, DDAVP-unresponsive type 1 or 2 VWD, and increasingly considered for HA replacement therapy.

Conclusions:

• The FVIII/VWF complex is fundamental to hemostasis, with VWF playing critical roles in FVIII's activity and stability.
• Plasma-derived FVIII/VWF concentrates are safe and effective therapeutic options for specific VWD types and HA.
• Adherence to national and international guidelines ensures the correct and optimal use of FVIII/VWF concentrates in clinical practice.