Clinical diagnosis of von Willebrand disease.

Abstract

von Willebrand disease (VWD) is the most frequent inherited bleeding disorder and is caused by quantitative (Types 1 and 3) or qualitative (Type 2) defects of von Willebrand factor (VWF). VWD is inherited by autosomal dominant or recessive pattern, but women with milder VWD forms seem to be more symptomatic than men. Mild VWD forms are both under- and misdiagnosed. The clinical expression of VWD is usually mild in Type 1, increasing in severity in Types 2 and 3. Mucocutaneous bleeding (epistaxis, menorrhagia) is a typical manifestation of the disease, and bleeding after dental extraction is the most frequent postoperative bleeding type. Because FVIII levels are usually only slightly reduced in most VWD types, spontaneous haemarthroses or haematomas are rare in VWD Types 1, 2A and 2B, whereas in Type 3 the severity of bleeding may resemble haemophilia. In Type 1 VWD, bleeding after delivery is rare because FVIII/VWF levels become normal at the end of pregnancy. Post-operative bleeding may not occur in Type 1 VWD patients, but in Type 3 VWD, prophylaxis is always required. Only a few retrospective studies on clinical diagnosis of VWD are available. In the 1234 cases enrolled by an Italian retrospective study, diagnosis of Types 1, 2 and 3 VWD occurred in young adults (83%), mainly in women (57%). Mucosal bleeding (64%) was more frequent than haematomas or haemarthrosis (15%), and 63% of patients did not require transfusions. In a more recent Italian prospective study (815/1234 cases observed for 1 year in 6/16 Italian centres), only 147 (18%) VWD patients showed bleeding episodes (n = 318) and minor or major surgeries (n = 87).