Federici Augusto B, Mannucci Pier Mannuccio
Angelo Bianchi Bonomi Haemophilia and Thrombosis Centre, Department of Medicine and Medical Specialities, IRCCS Maggiore Policlinico Hospital, Mangiagalli and Regina Elena Foundation and University of Milan, Milan, Italy.
Ann Med. 2007;39(5):346-58. doi: 10.1080/07853890701513738.
Von Willebrand disease (VWD) is the most frequent inherited bleeding disorder and is due to quantitative (types 1 and 3) or qualitative (type 2) defects of von Willebrand factor (VWF). VWD is inherited by autosomal dominant or recessive patterns, but women with mild forms are more symptomatic. VWD is classified in six VWD types (1, 2A, 2B, 2M, 2N, 3) with peculiar phenotype and genotype. The ristocetin cofactor activity (VWF:RCo) is the most useful test for VWD diagnosis, because it can mimic the interactions of VWF with its platelet receptor. Knowledge of the segments of VWF involved in the binding to its receptor and to factor VIII prompted the search for mutations in specific exons of the VWF gene, with mutations causing VWD types 2A, 2B, 2M, 2N localized in exons 18-28. In case of VWD types 1 and 3 the mutations are spread within the entire gene. Desmopressin (DDAVP) is the treatment of choice for type 1 VWD because it can induce release of normal VWF from cellular compartments. In type 3 and in severe forms of types 1 and 2 VWD, DDAVP is not effective and plasma virally inactivated VWF concentrates should be used in bleedings, surgery, and secondary long-term prophylaxis.
血管性血友病（VWD）是最常见的遗传性出血性疾病，由血管性血友病因子（VWF）的数量（1型和3型）或质量（2型）缺陷引起。VWD以常染色体显性或隐性模式遗传，但症状较轻的女性更易出现症状。VWD分为六种类型（1型、2A型、2B型、2M型、2N型、3型），各有独特的表型和基因型。瑞斯托霉素辅因子活性（VWF:RCo）是VWD诊断中最有用的检测方法，因为它可以模拟VWF与其血小板受体的相互作用。了解VWF与受体及因子VIII结合所涉及的片段，促使人们在VWF基因的特定外显子中寻找突变，导致2A型、2B型、2M型、2N型VWD的突变位于外显子18 - 28。对于1型和3型VWD，突变则分布在整个基因中。去氨加压素（DDAVP）是1型VWD的首选治疗方法，因为它可以诱导正常VWF从细胞区室释放。对于3型以及1型和2型的严重形式，DDAVP无效，在出血、手术及二级长期预防中应使用经病毒灭活的血浆VWF浓缩物。
