Current Management of von Willebrand Disease

Abstract

Table 1 shows the relative frequency of bleeding symptoms in three large series of patients diagnosed at specialised centres. Several attempts were recently made to evaluate the sensitivity and specificity of bleeding symptoms, especially in the mild cases with VWD1 and VWF: RCo (>20U/dl). In a multicentre study carried out in obligatory carriers of VWD1, menorrhagia and epistaxis were poor predictors of the disease, while cutaneous bleeding and bleeding after dental extractions were more sensitive symptoms for diagnosis. 9 A bleeding severity score (BSS) has been analysed in affected and non-affected members of 154 families enrolled prospectively in a large European study on VWD1. 10 Despite the fact that this BSS was investigated prospectively in VWD1, this approach can be useful in all VWD, as was recently proposed in a prospective study. 11The diagnosis of VWD, particularly VWD1, may require several laboratory tests to be repeated on different occasions. These tests are usually applied for patients with suspected bleeding disorders. Table 2 summarises the different steps for VWD diagnosis. The bleeding time (BT), an original hallmark of the disease, is not always prolonged and may be normal in patients with mild forms of VWD, such as those with VWD1 and normal platelet VWF content. 4 It is therefore not particularly useful for diagnosis. Evaluation of closure time (CT) with the platelet function analyser (PFA-100) gives a rapid and simple measure of VWF-dependent platelet function at high shear stress. It can be performed in whole blood and can be employed instead of the BT in children or when the BT is not feasible. This system is sensitive and reproducible for VWD screening. The computerised axial tomography (CT) scan is normal in VWD2N and cannot be modified in VWD3 after the administration of VWF/FVIII concentrates. 12 Based on these observations, BT and CT were not introduced in the flow chart to be used in the differential diagnosis of VWD types (see Figure 2). Molecular and pre-natal diagnoses of VWD have been in use since the early 1990s. The first mutations were found within exon-28 of the VWF gene that is responsible for domains A1, A2 and A3. Most VWD2A cases are due to missense mutations in the A1 domain, with