Toward Personalized Treatment for Patients with Low von Willebrand Factor and Quantitative von Willebrand Disease

The biological mechanisms involved in the pathogenesis of type 2 and type 3 von Willebrand disease (VWD) have been studied extensively. In contrast, although accounting for the majority of VWD cases, the pathobiology underlying partial quantitative VWD has remained somewhat elusive. However, important insights have been attained following several recent cohort studies that have investigated mechanisms in patients with type 1 VWD and low von Willebrand factor (VWF), respectively. These studies have demonstrated that reduced plasma VWF levels may result from either (1) decreased VWF biosynthesis and/or secretion in endothelial cells and (2) pathological increased VWF clearance. In addition, it has become clear that some patients with only mild to moderate reductions in plasma VWF levels in the 30 to 50 IU/dL range may have significant bleeding phenotypes. Importantly in these low VWF patients, bleeding risk fails to correlate with plasma VWF levels and inheritance is typically independent of the VWF gene. Although plasma VWF levels may increase to>50 IU/dL with progressive aging or pregnancy in these subjects, emerging data suggest that this apparent normalization in VWF levels does not necessarily equate to a complete correction in bleeding phenotype in patients with partial quantitative VWD. In this review, these recent advances in our understanding of quantitative VWD pathogenesis are discussed. Furthermore, the translational implications of these emerging findings are considered, particularly with respect to designing personalized treatment plans for VWD patients undergoing elective procedures.

Automated summary

Research has extensively studied the biological mechanisms involved in the pathogenesis of type 2 and type 3 von Willebrand disease (VWD). However, the pathobiology underlying partial quantitative VWD, which accounts for the majority of VWD cases, has remained somewhat elusive. Recent cohort studies have shown that reduced plasma VWF levels in these patients may result from decreased biosynthesis and/or secretion in endothelial cells, or from pathological increase in VWF clearance. Additionally, it has been found that some patients with mild to moderate reductions in plasma VWF levels may still exhibit significant bleeding phenotypes, and an increase in VWF levels may not necessarily equate to a complete correction in bleeding phenotype.