What makes von Willebrand factor (VWF) essential for normal blood clotting? This review explores the biochemistry and genetics of VWF, a crucial blood glycoprotein involved in hemostasis. It highlights how deficiencies in VWF lead to von Willebrand disease (VWD), the most common inherited bleeding disorder. The research examines VWF's role in platelet adhesion to damaged blood vessels through interactions with specific platelet membrane glycoproteins and connective tissue components. This paper discusses how these interactions are regulated by allosteric mechanisms and hydrodynamic shear forces. VWF acts as a carrier protein for clotting factor VIII, crucial for its survival in circulation. Mutations causing VWD disrupt VWF's complex biosynthetic process, affecting assembly, intracellular targeting, and secretion. Other mutations impair VWF's survival or ligand binding. Understanding VWF synthesis, structure, and function is crucial for classifying VWD based on distinct pathophysiologic mechanisms. These mechanisms correlate with clinical symptoms and therapy response. Integrating mental health interventions with substance abuse treatment can address the parenting needs of drug-dependent women.
As a review in the Annual Review of Biochemistry, this article synthesizes current knowledge on von Willebrand factor (VWF), fitting the journal's scope of comprehensive biochemical analyses. It builds upon previous research by summarizing recent findings about VWF's synthesis, structure, and function. By correlating pathophysiologic mechanisms with clinical outcomes, this review significantly advances the understanding and classification of VWD.