National Institute of Immunohaematology (ICMR), KEM Hospital, Parel, Mumbai, India.
Semin Thromb Hemost. 2011 Jul;37(5):595-601. doi: 10.1055/s-0031-1281048. Epub 2011 Nov 18.
Von Willebrand disease (VWD) in all developing countries including India is considered a rare coagulation disorder, contrary to many reports from Western countries. Prevalence data based on hospital referrals identifies type 3 VWD as the most common subtype followed by type 1 and type 2. Approximately 60 to 70% cases of type 3 VWD are reportedly born of consanguineous marriages. The discriminatory diagnostic tests mainly include assays for factor (F)VIII:C and ristocetin-induced platelet agglutination and Von Willebrand factor (VWF) antigen either by immunoelectrophoresis or by enzyme-linked immunosorbent assay. VWD-type assisting tests like VWF collagen binding, VWF ristocetin cofactor assay, VWF-FVIII binding assay, and multimer analysis are occasionally used but not routinely applied in many laboratories. Among women, menorrhagia is an important presenting manifestation. Except for a handful of centers mainly in metropolitan cities, most laboratories in the remote parts of the country have no facilities for VWD-related investigations, resulting in occasional misdiagnoses of VWD as hemophilia A. Genetic diagnosis is being offered in two or three centers using the indirect linkage method in type 3 VWD, and efforts are continuing to implementing a direct mutation detection technique for routine practice in a few laboratories. Depending on the subtype or the severity of VWD, desmopressin, cryoprecipitate, fresh-frozen plasma, and factor VIII/VWF concentrates are used for management. Antifibrinolytic agents like epsilon-aminocaproic acid and tranexamic acid are widely used as an adjuvant therapy. In women with menorrhagia, oral contraceptives as a supplementary treatment are also being widely advocated to reduce bleeding. Products like danazol, ethenyl estradiol, thalidomide, and atorvastatin have been used in individual patients; acquired VWD associated with hypothyroidism has been managed successfully with thyroid hormone treatment. Both minor and major surgical procedures are performed in a few centers with judicious use of cryoprecipitate or FVIII concentrate containing VWF along with other supplementary therapeutic products to achieve adequate hemostasis. Awareness about the disease, establishment of the comprehensive coagulation laboratory, and treatment centers will be successful in increasing diagnosis of VWD and consequently better management of affected patients. This is likely to tilt the ratios of different VWD types, and VWD is likely to emerge as the most common of all coagulation disorders in the near future.
在所有发展中国家，包括印度，血管性血友病（von Willebrand disease，VWD）被认为是一种罕见的凝血障碍疾病，与许多来自西方国家的报告相反。基于医院转诊的患病率数据表明，3 型 VWD 是最常见的亚型，其次是 1 型和 2 型。据报道，大约 60%至 70%的 3 型 VWD 病例是由近亲结婚所生。主要的鉴别诊断检测包括因子（factor，F）VIII:C 和瑞斯托霉素诱导的血小板聚集以及 Von Willebrand 因子（von Willebrand factor，VWF）抗原的检测，这些检测可通过免疫电泳或酶联免疫吸附试验进行。VWD 辅助检测，如 VWF 胶原结合、VWF 瑞斯托霉素辅因子检测、VWF-FVIII 结合检测和多聚体分析，偶尔会被使用，但在许多实验室中并没有常规应用。在女性中，月经过多是一种重要的临床表现。除了少数主要在大都市的中心外，该国偏远地区的大多数实验室都没有进行 VWD 相关检查的设施，这导致偶尔会将 VWD 误诊为血友病 A。目前，有两三个中心正在使用间接连锁法对 3 型 VWD 进行基因诊断，并且正在努力在少数实验室中实施常规的直接突变检测技术。根据 VWD 的亚型或严重程度，可使用去氨加压素、冷沉淀、新鲜冷冻血浆和因子 VIII/VWF 浓缩物进行治疗。抗纤维蛋白溶解剂如氨甲环酸和氨甲苯酸被广泛用作辅助治疗。对于月经过多的女性，口服避孕药作为补充治疗也被广泛提倡以减少出血。达那唑、乙烯雌二醇、沙利度胺和阿托伐他汀等药物已被用于个别患者；与甲状腺功能减退相关的获得性 VWD 已成功地通过甲状腺激素治疗进行管理。在少数中心，可谨慎使用冷沉淀或含有 VWF 的 FVIII 浓缩物，以及其他辅助治疗产品，进行小手术和大手术，以实现充分止血。提高对该疾病的认识、建立全面的凝血实验室和治疗中心，将有助于提高 VWD 的诊断率，并因此更好地管理受影响的患者。这可能会改变不同 VWD 类型的比例，在不久的将来，VWD 可能会成为所有凝血障碍疾病中最常见的一种。
