New treatment approaches to von Willebrand disease

Abstract

von Willebrand disease (VWD) is the commonest inherited bleeding disorder and results from either a quantitative or qualitative deficiency in the plasma glycoprotein von Willebrand factor (VWF). Recent large cohort studies have significantly enhanced our understanding of the molecular mechanisms involved in the pathogenesis of VWD. In contrast, however, there have been relatively few advances in the therapeutic options available for the treatment of bleeding in patients with VWD. Established treatment options include tranexamic acid, 1-deamino-8-D-arginine vasopressin (DDAVP), and plasma-derived VWF concentrates. In addition, a recombinant VWF has also recently been developed. In this review, we focus on how recent insights into the clinical and molecular aspects underpinning VWD are already beginning to influence treatment in the clinic. For example, a number of different bleeding assessment tools (BATs) have been developed to objectively assess bleeding symptoms in patients with VWD. Interestingly, however, these BAT scores may also have an important role to play in predicting bleeding risk in VWD. Furthermore, recent studies have demonstrated that enhanced VWF clearance plays a critical role in the etiology of both type 1 and type 2 VWD. These findings have direct translational relevance with respect to the use of DDAVP in patients with VWD. As understanding of the mechanisms involved in VWD pathogenesis continues to advance, novel treatment options are likely to emerge. Critically, however, large adequately powered and stratified clinical trials will be required to address the outstanding questions that remain regarding VWD treatment optimization. Learning Objectives• The reader will recognize the various therapeutic options available for the treatment of von Willebrand disease (VWD), including the recently developed recombinant VWF concentrate • The reader will understand how emerging data regarding the molecular pathogenesis underlying VWD are influencing the design of personalized treatment regimens for individual patients with VWD

von Willebrand factor clearance – biological mechanisms and clinical significance

“…Collectively, these observations have led to concerns that the clinical efficacy of DDAVP administered at 12–24 hourly intervals may be attenuated in VWD patients with enhanced VWF clearance. Consequently, VWF‐containing concentrates may represent a longer‐lasting and more efficacious therapeutic option for these patients, particularly in the context of surgery or major bleeding complications (Lavin & O'Donnell, ). Critically, studies to date have shown that the half‐life of infused plasma‐derived VWF concentrates in type 1C patients is normal, suggesting that the enhanced clearance phenotype observed in most cases is primarily attributable to changes in the endogenous VWF molecule (e.g.…”

¿Qué avances recientes hay en el entendimiento, diagnóstico y tratamiento de la enfermedad de Von Willebrand?: una revisión de la literatura

“…Asimismo, la optimización del tratamiento a largo plazo de estos pacientes demanda la conducción de ensayos clínicos, con el objetivo de ofrecer mejor evidencia que permita tomar decisiones clínicas acertadas. Por otro lado, los avances en ingeniería genética resultan prometedores para proveer una terapia genética dirigida a pacientes con EVW (67).…”

“…Adicionalmente, deben tenerse en cuenta las recomendaciones para procedimientos quirúrgicos: cirugía menor, niveles de FVW:RCo ≥ 50 UI/dL el día del procedimiento y el primer día postoperatorio, y > 30 UI/dL 2 a 5 días postoperatorio, o hasta la caída de la escara. Cirugía mayor, los niveles de FVW:RCo deben ser 100 UI/dL el día del procedimiento y durante el primer día postoperatorio, y deben mantenerse ≥ 50 UI/dL de 7 a 14 días o hasta la cicatrización completa (67).…”

How I treat low von Willebrand factor levels

“…These VWF concentrates differ in several aspects, including source of plasma, purification methodology, viral inactivation steps, and FVIII content (recently reviewed by Lavin and O'Donnell). 51 In addition, a first recombinant VWF concentrate has recently been developed and licensed for use in some countries. 36…”