Type 1 von Willebrand disease due to reduced von Willebrand factor synthesis and/or survival: observations from a case series.

摘要

It may be difficult to diagnose type 1 von Willebrand disease (VWD) because of its heterogeneous and sometimes elusive nature. To evaluate the contribution of a shorter von Willebrand factor (VWF) survival in modulating VWD phenotype, the VWF half-life was assessed in 45 type 1 VWD patients using a 24-h 1-desamino-8-d-arginine vasopressin (DDAVP) test. A shorter VWF survival was observed in patients with C1130F mutations (T(1/2) elimination [T(1/2)el]=4.6+/-1.0h vs normal=15.8+/-2.3h, P<0.0001), in those with other missense mutations investigated (T(1/2)el=9.5+/-0.9h, P<0.02), and in patients not carrying VWF mutations (T(1/2)el=7.0+/-0.7h, P<0.001); the decrease mainly depended on a greater VWF clearance. VWF survival and clearance were normal in patients who carried nonsense mutations. The VWF-propeptide-to-VWF-antigen (VWF:Ag) ratio (VWFpp ratio) was higher in patients with a shorter VWF survival, and the values were inversely correlated with the VWF half-life (P<0.01). The response of VWF to DDAVP administration, which is useful to explore the synthesis and storage of VWF, was normal in patients with no mutations, whereas it decreased in patients with missense and nonsense mutations. Three scenarios, thus, are recognizable in type 1 VWD; one is associated mainly with a shorter survival of VWF, another is associated with its reduced synthesis and release, and a third is characterized by a combination of the two. The shorter VWF half-life found in patients with no VWF mutations suggests that mechanisms other than VWF might be involved in the pathogenesis of type 1 VWD.