Boissier E, Darnige L, Dougados J, Arlet J-B, Dupeux S, Georgin-Lavialle S, Caron C, Tapon-Bretaudière J, Pouchot J, Ranque B
Service de médecine interne, hôpital européen Georges-Pompidou, AP-HP, 20, rue Leblanc, 75015 Paris, France.
Service d'hématologie, hôpital européen Georges-Pompidou, AP-HP, 20, rue Leblanc, 75015 Paris, France.
Rev Med Interne. 2014 Mar;35(3):154-9. doi: 10.1016/j.revmed.2013.02.039. Epub 2013 Jun 7.
Whereas von Willebrand disease is the most common constitutional bleeding disorder, acquired von Willebrand syndrome is rare.
Retrospective, monocentric descriptive study of consecutive cases of acquired von Willebrand syndrome diagnosed between 2000 and 2012. Diagnostic criteria included: absence of a past history of mucocutaneous bleeding, with low plasma levels of factor VIII (FVIII) and von Willebrand factor (VWF), ristocetine cofactor activity (RCo) and antigen (Ag).
Nine men were diagnosed with von Willebrand syndrome. Six of them presented with recent mucocutaneous bleeding. In eight cases, the biological phenotype was a type 2 von Willebrand disease, with decreased VWF:RCo/VWF:Ag ratio. A lymphoproliferative disease with circulating paraprotein was identified in all patients, including one chronic lymphoid leukemia, three Waldenström and one marginal zone lymphomas, four monoclonal gammapathies of unknown significance. Screening for an anti-VWF inhibitor was negative. Symptomatic treatment using infusion of VWF concentrates was administrated in the presence of severe mucocutaneaous bleeding. Five patients received intravenous immunoglobulins with a good response only in patients with G isotype paraprotein. A chemotherapy was initiated if indicated for the underlying disorder. Three of the four patients who achieved remission of the associated lymphoma had a subsequent improvement of plasma VWF levels, while all other patients remained deficient.
Acquired von Willebrand syndrome is a rare but potentially serious disease. The diagnostic should be suspected in adults with unusual mucocutaneous bleeding, with or without prolonged partial thromboplastin time (PTT), and confirmed with a decreased plasma level of VWF (Ag and RCo). An associated haematological, neoplastic or cardiac valvular disease must be searched.
血管性血友病是最常见的遗传性出血性疾病，而获得性血管性血友病综合征较为罕见。
对2000年至2012年间确诊的获得性血管性血友病综合征连续病例进行回顾性、单中心描述性研究。诊断标准包括：无黏膜皮肤出血既往史，血浆中因子VIII（FVIII）、血管性血友病因子（VWF）、瑞斯托霉素辅因子活性（RCo）及抗原（Ag）水平降低。
9名男性被诊断为血管性血友病综合征。其中6人近期出现黏膜皮肤出血。8例患者的生物学表型为2型血管性血友病，VWF:RCo/VWF:Ag比值降低。所有患者均确诊有一种伴有循环副蛋白的淋巴增殖性疾病，包括1例慢性淋巴细胞白血病、3例华氏巨球蛋白血症、1例边缘区淋巴瘤以及4例意义未明的单克隆丙种球蛋白病。抗VWF抑制剂筛查结果为阴性。在出现严重黏膜皮肤出血时，采用输注VWF浓缩物进行对症治疗。5例患者接受了静脉注射免疫球蛋白治疗，仅G同种型副蛋白患者反应良好。如有指征，针对基础疾病启动化疗。4例相关淋巴瘤缓解的患者中有3例随后血浆VWF水平有所改善，而其他所有患者仍存在缺乏状态。
获得性血管性血友病综合征是一种罕见但可能严重的疾病。对于有异常黏膜皮肤出血的成人，无论部分凝血活酶时间（PTT）是否延长，均应怀疑该病，并通过血浆VWF（Ag和RCo）水平降低来确诊。必须排查是否存在相关的血液系统、肿瘤性或心脏瓣膜疾病。
