Key outstanding questions for future study in low VWF
| 1. What is the genetic basis underlying the reduction in plasma VWF levels in families with low VWF levels in whom no VWF gene sequence variants have been identified? |
| 2. In families with low VWF due to other genetic loci, what is the inheritance pattern, and how does bleeding phenotype relate to low VWF levels? |
| 3. What are the molecular mechanisms underpinning low VWF levels? In particular, what is the relative importance of reduced endothelial cell synthesis/secretion vs enhanced circulatory clearance? |
| 4. In establishing the diagnosis of low VWF, should a specific BAT score be preferred? |
| 5. For patients with low plasma VWF on initial testing, what is the optimal time frame for performing repeat VWF testing to confirm an accurate diagnosis of low VWF? |
| Conversely, is there a threshold plasma VWF level (even allowing for acute phase–induced transient increases in plasma VWF) above which retesting is not in order? |
| 6. Why is HMB such a common clinical presentation in women with low VWF levels? Does this simply relate to the hemostatic function of VWF or might other emerging biological functions of VWF (eg, regulation of angiogenesis) also be of importance? |
| 7. Are DDAVP trials necessary for patients with low VWF? |
| 8. In managing women with low VWF peripartum, what target plasma VWF levels should be used to reduce the high reported rates of primary and secondary PPH? |
| 9. How should minor and major surgery be managed in patients with low VWF who have a very significant bleeding history? Is correction of the mild reduction in plasma VWF levels adequate to completely revert the bleeding phenotype? |
| 10. Recent data have shown that plasma VWF levels often correct to within the “normal” range (50-150 IU/dL) in patients with low VWF with aging. Does this mean that the bleeding phenotype has been ameliorated, especially in patients with a previously severe bleeding phenotype? |
| 1. What is the genetic basis underlying the reduction in plasma VWF levels in families with low VWF levels in whom no VWF gene sequence variants have been identified? |
| 2. In families with low VWF due to other genetic loci, what is the inheritance pattern, and how does bleeding phenotype relate to low VWF levels? |
| 3. What are the molecular mechanisms underpinning low VWF levels? In particular, what is the relative importance of reduced endothelial cell synthesis/secretion vs enhanced circulatory clearance? |
| 4. In establishing the diagnosis of low VWF, should a specific BAT score be preferred? |
| 5. For patients with low plasma VWF on initial testing, what is the optimal time frame for performing repeat VWF testing to confirm an accurate diagnosis of low VWF? |
| Conversely, is there a threshold plasma VWF level (even allowing for acute phase–induced transient increases in plasma VWF) above which retesting is not in order? |
| 6. Why is HMB such a common clinical presentation in women with low VWF levels? Does this simply relate to the hemostatic function of VWF or might other emerging biological functions of VWF (eg, regulation of angiogenesis) also be of importance? |
| 7. Are DDAVP trials necessary for patients with low VWF? |
| 8. In managing women with low VWF peripartum, what target plasma VWF levels should be used to reduce the high reported rates of primary and secondary PPH? |
| 9. How should minor and major surgery be managed in patients with low VWF who have a very significant bleeding history? Is correction of the mild reduction in plasma VWF levels adequate to completely revert the bleeding phenotype? |
| 10. Recent data have shown that plasma VWF levels often correct to within the “normal” range (50-150 IU/dL) in patients with low VWF with aging. Does this mean that the bleeding phenotype has been ameliorated, especially in patients with a previously severe bleeding phenotype? |