背景：血管性血友病（von Willebrand disease，VWD）是一种因编码血管性血友病因子（von Willebrand factor，VWF）的基因突变引起血浆VWF数量减少或质量异常的遗传性出血性疾病。临床上常见，国外报道发病率约为1/1000，国内因部分实验室检查尚未普及、大量轻症患者表现不明显或疾病意识较低的原因诊断率远低于此，更难以精准分型和管理。本病临床表现主要为皮肤、黏膜出血，重者可有内脏出血，关节、肌肉血肿较少见。目前以去氨加压素（DDAVP）与替代治疗为主，缺乏更为精准的治疗方式。2011年中国医学科学院血液学研究所团队对VWD患者的临床研究表明我国对VWD患者的管理仍处于早期阶段，VWD在我国的误诊率较高，对月经过多女性和贫血女性的漏诊多。2023年昆明医科大学团队发表了一项在线问卷研究，该研究结果表明我国VWD患者的初始出血事件发生早，临床表现异质性高，促进了对VWD的认识及管理。然而目前尚未有关于VWD全国大规模多维度的真实世界研究。本研究纳入全国血友病登记系统自2011年以来所有的VWD患者，对其人口学特征、临床特征、简明MCMDM-1VWD出血评分、ISTH-BAT出血评分、治疗情况进行分析。

目的：研究中国VWD患者的临床特征与疾病需求，促进诊断、治疗可及性的提高，改善患者生活质量。

方法：本研究纳入全国血友病登记系统2011年1月1日至2023年10月1日之间所有的VWD患者人口统计学信息、临床特征、治疗情况进行分析。电话随访患者出血评分并整理分析。

结果：1.一般特征：1型VWD（144，24.9%）和3型（140，24.9%）最多，不能分型的占到41.5%。2型（54，9.3%）最少。儿童多于成人（59.7%VS40.3%），男性多于女性（57.1%VS42.9%），O型血最多（92，43.2%），AB血（19，8.9%）最少。2.诊断情况：中位诊断年龄为13（26.7）岁，其中1型VWD中位诊断年龄比3型中位诊断年龄平均延迟6.9年（P＜0.05），79.8%患者诊断延迟，其中3型诊断延迟率最低，为46.8%（P＜0.05）。3.出血情况：最常见症状为鼻出血（200，79.4%）、女性平均出血评分比男性高2.1~2.2分（P＜0.05），女性患者超过一半以上有月经过多/生产出血的情况。VWF：Ag、FVIII：C与出血评分呈负相关，VWF：Ag、FVIII:C数值越低，则出血评分越高。4.治疗情况：按需治疗最常用新鲜冰冻血浆（148，58.7%）。预防治疗25例（9.9%）最常用FVIII浓缩制剂。5.基因突变：最常见突变类型是错义突变（58，69%），16例（23.5%）患者合并有其他遗传性凝血因子缺乏的基因突变。

结论：我们首次报告了国内规模最大、最全面的VWD患者队列，描述了我国不同分型VWD患者的临床特征，特别是疾病对女性的影响，分析了ABO血型对VWD疾病的影响，明确VWF：Ag、FVIII：C与出血评分呈负相关。目前我国VWD诊疗主要存在诊断延迟、用药不便的问题，希望本研究能加强医护与患者对现状的了解，普及确诊和分型的实验室检查，随着重组凝血因子制剂的发展，VWD患者的治疗将开启新篇章。

Background：Von Willebrand disease(VWD) is a hereditary hemorrhagic disease caused by mutations in the von Willebrand factor (VWF) gene, leading to a decrease in plasma VWF quantity or abnormal quality. It is common clinically, and the incidence rate reported abroad is about 1/1000. In China, because some laboratory tests have not been popularized, the diagnosis rate of a large number of patients with mild diseases is far lower than this, and it is more difficult to accurately classify and manage. The clinical manifestations of this disease are mainly skin and mucosal bleeding, and in severe cases, visceral bleeding may occur. Hematomas in joints and muscles are relatively rare. At present, the main treatment options are desmopressin (DDAVP) and alternative therapy, but there is a lack of more precise treatment methods. In 2011, a clinical study conducted by a team from the Institute of Hematology& Blood Diseases Hospital，Chinese Academy of Medical Sciences& Peking Union Medical Collegeshowed that the care for VWD patients in China is still in the early stage, with a high misdiagnosis rate of VWD in China, as well as missed diagnosis for women with excessive menstruation and anemia. In 2023, a team from Kunming Medical University published an online questionnaire study, which showed that initial bleeding events occurred early in VWD patients in China, with high heterogeneity in clinical manifestations, promoting awareness and management of VWD. However there is no large-scale multidimensional real-world study of VWD nationwide. This study included all VWD patients in the National Hemophilia Registry since 2011 and examined their demographic characteristics, clinical characteristics, condensed MCMDM-1vWD and ISTH-BAT bleeding scores, treatment, and health-related quality of life. 

Objective：To study the clinical characteristics and needs of Chinese VWD patients, promote the accessibility of diagnosis and treatment, and improve the quality of life of patients.

Methods：This study included demographic information, clinical characteristics, and treatment status of all VWD patients enrolled in the National Hemophilia Registry for analysis. Follow up the patients' bleeding scores and analyze them.

Results:1. General characteristics: type 1 VWD (144, 24.9%) and type 3 (140 cases, 24.9%) were the most common, and 41.5% could not be classified. Type 2 (54 cases, 9.3%) was the least. There were more children than adults (59.7% vs. 40.3%), more men than women (57.1% vs. 42.9%), the highest blood type O (92, 43.2%), and the least AB blood (19, 8.9%). 2. Diagnosis: The overall median age of diagnosis was 13 (26.7) years, and the median age of diagnosis of type 1 VWD was 6.9 years later than that of type 3 (P<0.05), and 79.8% of patients had a delay in diagnosis, and the delay rate of type 3 was the lowest(46.8%) (P<0.05). 3. Bleeding: The most common symptom was nosebleeds (79.4%), and the average bleeding score of women was 2.1~2.2 points higher than that of men (P<0.05).More than half of female patients have menorrhagia/bleeding during childbirth.VWF:Ag and FVIII:C were negatively correlated with bleeding scores, and the lower the VWF:Ag and FVIII:C values, the higher the bleeding scores. 4. Treatment: Fresh frozen plasma (148, 58.7%) was the most commonly used for on-demand treatment. Twenty-five patients (9.9%) were most commonly treated with FVIII concentratefor preventive treatment. 5. Gene mutations: The most common type of mutation was missense mutations (58.69%), and 16 patients (23.5%) had gene mutations with other hereditary coagulation factor deficiencies.

Conclusions:For the first time, we reported the largest and most comprehensive cohort of VWD patients in China, described the clinical characteristics of patients with different types of VWD in China,especially the impact of disease on women,analyzed the effect of ABO blood group on VWD disease, and confirmed that VWF:Ag and FVIII:C were negatively correlated with bleeding scores. It is hoped that this study can strengthen the understanding of the current situation of medical care and patients, popularize laboratory tests for diagnosis and classification, and open a new chapter in the treatment of VWD patients with the development of recombinant coagulation factor preparations.